Clinical trial NCT04495140: Study To Characterize Mass Balance, Absolute Bioavailability, Fraction Absorbed And Pharmacokinetics Of 14C PF-06882961
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: bioavailability
excretion
metabolism
absorption
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-07-31
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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.

Primary outcomes:
measure: Total recovery of radioactivity in urine and feces, following oral administration of [14C] PF-06882961 in period 1
timeFrame: Baseline through approximately hour 312 (day 14). Period 1 is 14 days
Secondary outcomes:
measure: Metabolite profiling/identification in plasma, urine, and feces
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96-312 hour (hr)
measure: Plasma Cmax to describe plasma PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Plasma Tmax to describe the PK of total radioactivity following administration of single, oral dose of [14C]PF-06882961
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Plasma AUClast to describe PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Plasma AUCinf to describe plasma PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Plasma elimination t½ to describe plasma PK of total radioactivity following administration of single, oral dose of [14C] PF-06882961
timeFrame: 00, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Plasma Cmax to describe the plasma PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Plasma Tmax to describe the plasma PK of PF-06882961 following administration of single, oral dose of [14C]PF-06882961
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Plasma AUClast to describe PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Plasma AUCinf to describe plasma PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Mean residence Time (MRT )following administration of a single, intravenous dose of [14C]PF 06882961
timeFrame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 hr
measure: Systemic Clearance (CL) following administration of a single, intravenous dose of [14C]PF 06882961
timeFrame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 hr
measure: Volume of distribution at steady state (Vss) following administration of a single, intravenous dose of [14C]PF 06882961
timeFrame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 hr
measure: Absolute oral bioavailability (F)
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Fraction of dose absorbed following single oral administration of [14C]PF-06882961
timeFrame: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96-312hr
measure: Number of participants with adverse events
timeFrame: Baseline in Period 1 up to 32 days after the period 2 doses, for a total of approximately 46 days
measure: Plasma elimination t½ to describe plasma PK of PF-06882961 following administration of single, oral dose of [14C] PF-06882961
timeFrame: 00, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hr
measure: Number of participants with safety laboratory test results above/below certain threshold
timeFrame: baseline, day 5-14 of period 1 (period 1 is 14 days), day 3-8 of period 2 (period 2 is 8 days)
measure: Number of participants with ECG measurements above/below certain threshold
timeFrame: baseline, day 5-14 of period 1 (period 1 is 14 days), day 3-8 of period 2 (period 2 is 8 days)
measure: Number of participants with vital measurements above/below certain threshold
timeFrame: baseline, day 5-14 of period 1 (period 1 is 14 days), day 3-8 of period 2 (period 2 is 8 days)
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: PRA Health Sciences
city: Utrecht
country: Netherlands
facility: PRA Health Sciences Utrecht
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: