Study To Characterize Mass Balance, Absolute Bioavailability, Fraction Absorbed And Pharmacokinetics Of 14C PF-06882961

• ClinicalTrials.gov Identifier: NCT04495140
• Recruitment Status: Completed
• First Posted: July 31, 2020
• Last Update Posted: November 25, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

This study is a Phase 1, open-label, non-randomized, 2-period, fixed sequence study to characterize the metabolic profile and routes of excretion of oral [14C]PF-06882961 and to evaluate the absolute oral bioavailability of PF-06882961 and fraction absorbed of [14C]PF-06882961 in reference to intravenous [14C]PF-06882961 in healthy male participants.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteer	Drug: [14C]PF-06882961, 50 mg; Drug: PF-06882961, 50 mg and [14C]PF-06882961, 100 ug	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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-06882961
• Actual Study Start Date: July 22, 2020
• Actual Primary Completion Date: October 15, 2020
• Actual Study Completion Date: October 15, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Oral [14C]PF-06882961, 50 mg; In this arm, a single oral dose of [14C]PF-06882961, 50 mg will be administered as a liquid formulation.	Drug: [14C]PF-06882961, 50 mg; A single oral dose of [14C]PF-06882961, will be administered as a liquid formulation.
Experimental: Oral PF-06882961 50 mg and intravenous [14C]PF-06882961 100 ug; In this arm, single oral dose of unlabeled PF-06882961, 50 mg will be administered as a liquid formulation. Approximately 3 hours after the administration of the unlabeled oral dose, a single dose of [14C]PF-06882961, 100 ug, will be administered via intravenous infusion.	Drug: PF-06882961, 50 mg and [14C]PF-06882961, 100 ug; A single, oral, unlabeled dose of PF-06882961, 50 mg will be administered as a liquid formulation. Approximately 3 hours after the administration of the unlabeled oral dose, a single dose of [14C]PF-06882961 will be administered via intravenous infusion.

Outcome Measures

Primary Outcome Measures :

1. Total recovery of radioactivity in urine and feces, following oral administration of [14C] PF-06882961 in period 1 [ Time Frame: Baseline through approximately hour 312 (day 14). Period 1 is 14 days ]
   Total recovery of radioactivity in urine and feces, and both routes combined, expressed as a percent of total oral radioactive dose administered.

Secondary Outcome Measures :

1. Metabolite profiling/identification in plasma, urine, and feces [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96-312 hour (hr) ]
   Metabolic profiling/identification and determination of relative abundance of [14C]PF-06882961 and the metabolites of [14C]PF-06882961 in plasma, urine, and feces.
2. Plasma Cmax to describe plasma PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961 [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
   Maximum Observed Plasma Radioactivity
3. Plasma Tmax to describe the PK of total radioactivity following administration of single, oral dose of [14C]PF-06882961 [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
   Time to Reach Maximum Observed Plasma Radioactivity
4. Plasma AUClast to describe PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961 [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
   Area under the plasma radioactivity-time profile from time 0 to time of the last quantifiable concentration (Clast)
5. Plasma AUCinf to describe plasma PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961 [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
   AUCinf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
6. Plasma elimination t½ to describe plasma PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961 [ Time Frame: 00, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
   Plasma elimination half-life is the time measured for the plasma radioactivity to decrease by one half.
7. Plasma Cmax to describe the plasma PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961 [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
   Maximum Observed Plasma Concentration
8. Plasma Tmax to describe the plasma PK of PF-06882961 following administration of single, oral dose of [14C]PF-06882961 [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
   Time to Reach Maximum Observed Plasma Concentration
9. Plasma AUClast to describe PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961 [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
   Area under the plasma concentration-time profile from time 0 to time of the last quantifiable concentration (Clast)
10. Plasma AUCinf to describe plasma PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961 [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
    AUCinf is Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
11. Mean residence Time (MRT )following administration of a single, intravenous dose of [14C]PF 06882961 [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 hr ]
    where MRT is the Mean Residence Time
12. Systemic Clearance (CL) following administration of a single, intravenous dose of [14C]PF 06882961 [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 hr ]
    Systemic clearance, CL is a quantitative measure of the rate at which a drug substance is removed from the body.
13. Volume of distribution at steady state (Vss) following administration of a single, intravenous dose of [14C]PF 06882961 [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 hr ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
14. Absolute oral bioavailability (F) [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
    Absolute oral bioavailability following administration of a single oral dose of PF-06882961 in reference to a single intravenous dose of [14C]PF-06882961
15. Fraction of dose absorbed following single oral administration of [14C]PF-06882961 [ Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96-312hr ]
    Fraction absorbed calculated from ratio of total urinary radioactivity following oral administration in reference to intravenous administration
16. Number of participants with adverse events [ Time Frame: Baseline in Period 1 up to 32 days after the period 2 doses, for a total of approximately 46 days ]
    adverse events
17. Plasma elimination t½ to describe plasma PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961 [ Time Frame: 00, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr ]
    Plasma elimination half-life is the time measured for the plasma radioactivity to decrease by one half.
18. Number of participants with safety laboratory test results above/below certain threshold [ Time Frame: baseline, day 5-14 of period 1 (period 1 is 14 days), day 3-8 of period 2 (period 2 is 8 days) ]
    lab tests
19. Number of participants with ECG measurements above/below certain threshold [ Time Frame: baseline, day 5-14 of period 1 (period 1 is 14 days), day 3-8 of period 2 (period 2 is 8 days) ]
    ECGs
20. Number of participants with vital measurements above/below certain threshold [ Time Frame: baseline, day 5-14 of period 1 (period 1 is 14 days), day 3-8 of period 2 (period 2 is 8 days) ]
    vitals

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 54 Years (Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Male participants between 18 to 54 years of age
• Healthy and capable of signing informed consent document
• Willing to comply to all scheduled visits, lab tests, lifestyle considerations and study procedures
• Body mass index (BMI) of 17.5 to 30 kg/m2; and a total body weight ≥50 kg (110 lb).

Exclusion Criteria:

• acute or chronic medical or psychiatric condition including recent (within the past year)
• Surgical procedures like gastrectomy, cholecystectomy, Irregularity in bowel movements
• Use of prescription or non-prescription drugs and dietary and herbal supplements within 14 days prior to the first dose of investigational product.
• Previous administration with an investigational drug within 60 days (or as determined by the local requirement) preceding the first dose of investigational product used in this study.
• Known prior participation in a trial involving PF-06882961 or known intolerance to a GLP-1R agonist.
• A positive urine drug test on screening or Day -1.
• Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
• Participants with abnormalities in clinical laboratory tests including ECGs, vital signs, liver function tests, myocardial infarction
• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed.
• History of alcohol or tobacco abuse or binge drinking and/or any other illicit drug use or dependence within past 6 months.
• Subjects whose occupation requires exposure to radiation or monitoring of radiation exposure.
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
• History of sensitivity to heparin or heparin-induced thrombocytopenia only if heparin is planned to flush intravenous catheters.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.

Contacts and Locations

Locations

Netherlands

PRA Health Sciences

Groningen, Netherlands, 9728 NZ

PRA Health Sciences Utrecht

Utrecht, Netherlands, 3584 BL

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04495140
• Other Study ID Numbers: C3421009; 2019-002584-10 ( EudraCT Number )
• First Posted: July 31, 2020
• Last Update Posted: November 25, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

bioavailability; excretion; metabolism; absorption