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

Healthy Volunteer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04495140
• Other study ID #: C3421009
• Secondary ID: 2019-002584-10
• Status: Completed
• Phase: Phase 1
• Start date: July 22, 2020
• Est. completion date: October 15, 2020

Study information

• Verified date: November 2020
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: October 15, 2020
• Est. primary completion date: October 15, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 54 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• [14C]PF-06882961, 50 mg
A single oral dose of [14C]PF-06882961, will be administered as a liquid formulation.
• 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.

Locations

Country	Name	City	State
Netherlands	PRA Health Sciences	Groningen
Netherlands	PRA Health Sciences Utrecht	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total recovery of radioactivity in urine and feces, following oral administration of [14C] PF-06882961 in period 1	Total recovery of radioactivity in urine and feces, and both routes combined, expressed as a percent of total oral radioactive dose administered.	Baseline through approximately hour 312 (day 14). Period 1 is 14 days
Secondary	Metabolite profiling/identification in plasma, urine, and feces	Metabolic profiling/identification and determination of relative abundance of [14C]PF-06882961 and the metabolites of [14C]PF-06882961 in plasma, urine, and feces.	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96-312 hour (hr)
Secondary	Plasma Cmax to describe plasma PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961	Maximum Observed Plasma Radioactivity	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Plasma Tmax to describe the PK of total radioactivity following administration of single, oral dose of [14C]PF-06882961	Time to Reach Maximum Observed Plasma Radioactivity	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Plasma AUClast to describe PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961	Area under the plasma radioactivity-time profile from time 0 to time of the last quantifiable concentration (Clast)	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Plasma AUCinf to describe plasma PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961	AUCinf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Plasma elimination t½ to describe plasma PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961	Plasma elimination half-life is the time measured for the plasma radioactivity to decrease by one half.	00, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Plasma Cmax to describe the plasma PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961	Maximum Observed Plasma Concentration	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Plasma Tmax to describe the plasma PK of PF-06882961 following administration of single, oral dose of [14C]PF-06882961	Time to Reach Maximum Observed Plasma Concentration	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Plasma AUClast to describe PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961	Area under the plasma concentration-time profile from time 0 to time of the last quantifiable concentration (Clast)	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Plasma AUCinf to describe plasma PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961	AUCinf is Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Mean residence Time (MRT )following administration of a single, intravenous dose of [14C]PF 06882961	where MRT is the Mean Residence Time	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 hr
Secondary	Systemic Clearance (CL) following administration of a single, intravenous dose of [14C]PF 06882961	Systemic clearance, CL is a quantitative measure of the rate at which a drug substance is removed from the body.	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 hr
Secondary	Volume of distribution at steady state (Vss) following administration of a single, intravenous dose of [14C]PF 06882961	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.	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 hr
Secondary	Absolute oral bioavailability (F)	Absolute oral bioavailability following administration of a single oral dose of PF-06882961 in reference to a single intravenous dose of [14C]PF-06882961	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Fraction of dose absorbed following single oral administration of [14C]PF-06882961	Fraction absorbed calculated from ratio of total urinary radioactivity following oral administration in reference to intravenous administration	0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96-312hr
Secondary	Number of participants with adverse events	adverse events	Baseline in Period 1 up to 32 days after the period 2 doses, for a total of approximately 46 days
Secondary	Plasma elimination t½ to describe plasma PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961	Plasma elimination half-life is the time measured for the plasma radioactivity to decrease by one half.	00, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
Secondary	Number of participants with safety laboratory test results above/below certain threshold	lab tests	baseline, day 5-14 of period 1 (period 1 is 14 days), day 3-8 of period 2 (period 2 is 8 days)
Secondary	Number of participants with ECG measurements above/below certain threshold	ECGs	baseline, day 5-14 of period 1 (period 1 is 14 days), day 3-8 of period 2 (period 2 is 8 days)
Secondary	Number of participants with vital measurements above/below certain threshold	vitals	baseline, day 5-14 of period 1 (period 1 is 14 days), day 3-8 of period 2 (period 2 is 8 days)

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