Clinical trial NCT04866225: A Study in Healthy Adult Male Participants to Assess Absorption, Distribution, Metabolism and Excretion (ADME) of Radiolabeled PF-06865571.
Official title: A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY IN HEALTHY ADULT MALE PARTICIPANTS TO ASSESS THE EXTENT OF EXCRETION, ABSOLUTE BIOAVAILABILITY, FRACTION ABSORBED, AND PHARMACOKINETICS OF [14C]PF-06865571 USING A 14C-MICROTRACER APPROACH
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: ADME
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-04-29
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: This study is a Phase 1, open-label, non-randomized, 2-period, fixed-sequence, single-dose study of PF-06865571 in healthy male participants to characterize the ADME properties of \[14C\]PF-06865571 following oral administration; and to evaluate the absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-06865571 following oral administration of unlabeled PF-06865571 and IV administration of \[14C\]PF-06865571.


Eligibility criteria: Inclusion Criteria:

* Male participants, 18 to 60 years of age, inclusive, at the time of signing the informed consent document.
* Male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac tests.
* Participants who are nonsmoking for at least 3 months at the time of signing the informed consent document.
* BMI of 17.5 to 30.4 kg/m2, inclusive; and a total body weight \>50 kg (110 lb).

Exclusion Criteria:

* Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
* History of irregular bowel movements including irritable bowel syndrome or frequent episodes of diarrhea or constipation, defined by less than 1 bowel movement on average per 2 days, or lactose intolerance.
* History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg,or HCVAb. Hepatitis B vaccination is allowed.
* History of SARS-CoV-2 PCR or antibody (eg, IgG, IgM, etc) positive result would necessitate accompanying history of asymptomatic state for at least 6 months prior to screening.
* Use of prescription or nonprescription drugs.
* Previous administration with an unapproved drug within 60 days preceding the first dose of study intervention used in this study.
* A positive urine drug test.
* A positive urine cotinine test.
* A positive COVID-19 (SARS-CoV-2) PCR test.
* Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.

Primary outcomes:
measure: Total Recovery of Radioactivity in Urine as Percentage of Total Radioactive Dose of PF-06865571 Administered
timeFrame: Period 1: Day -1 to maximum Day 21; Period 2: Day 1 to maximum Day 3
measure: Total Recovery of Radioactivity in Feces as Percentage of Total Radioactive Dose of PF-06865571 Administered
timeFrame: Period 1: Day -1 to maximum Day 21; Period 2: Day 1 to maximum Day 3
measure: Total Recovery of Radioactivity in Total Excreta (Urine + Feces) as Percentage of Total Radioactive Dose of PF-06865571 Administered
timeFrame: Period 1: Day -1 to maximum Day 21; Period 2: Day 1 to maximum Day 3
measure: Relative Abundance (Mean Value) of Radiolabeled PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: Relative Abundance (Mean Value) of Metabolites of Radiolabeled PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 3, 6, 12, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: Relative Abundance (Mean Value) of Radiolabeled PF-06865571 in Urine in Period 1
timeFrame: Period 1: Day -1 to maximum Day 21
measure: Relative Abundance (Mean Value) of Metabolites of Radiolabeled PF-06865571 in Urine in Period 1
timeFrame: Period 1: Day -1 to maximum Day 21
measure: Relative Abundance (Mean Value) of Radiolabeled PF-06865571 in Feces in Period 1
timeFrame: Period 1: Day -1 to maximum Day 21
measure: Relative Abundance (Mean Value) of Metabolites of Radiolabeled PF-06865571 in Feces in Period 1
timeFrame: Period 1: Day -1 to maximum Day 21
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Profile From Time Zero to Time of The Last Quantifiable Concentration (AUClast) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: Maximum Plasma Concentration (Cmax) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: Time for Cmax (Tmax) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: Terminal Elimination Half-life (t1/2) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: AUClast of Oral PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: Cmax of Oral PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: Tmax of Oral PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: AUCinf of Oral PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: t1/2 of Oral PF-06865571 in Plasma in Period 1
timeFrame: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
measure: AUClast of Intravenous (IV) Radiolabeled PF-06865571 in Plasma in Period 2
timeFrame: Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3)
measure: Cmax of IV Radiolabeled PF-06865571 in Plasma in Period 2
timeFrame: Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3)
measure: Tmax of IV Radiolabeled PF-06865571 in Plasma in Period 2
timeFrame: Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3)
measure: t1/2 of IV Radiolabeled PF-06865571 in Plasma in Period 2
timeFrame: Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3)
measure: AUCinf of IV Radiolabeled PF-06865571 in Plasma in Period 2
timeFrame: Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3)
measure: Systemic Clearance (CL) of IV Radiolabeled PF-06865571 in Plasma in Period 2
timeFrame: Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3)
measure: Steady State Volume of Distribution (Vss) of IV Radiolabeled PF-06865571 in Plasma in Period 2
timeFrame: Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3)
measure: Dose-Normalized AUCinf (AUCinf[dn]) of Oral Unlabeled PF-06865571 in Plasma in Period 2
timeFrame: Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3)
measure: AUCinf(dn) of IV Microtracer of Radiolabeled PF-06865571 in Plasma in Period 2
timeFrame: Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3)
measure: Absolute Oral Bioavailability (F) of Oral Unlabeled and IV Radiolabeled PF-06865571 for Plasma AUCinf(dn) in Period 2
timeFrame: Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3)
measure: Percentage of Total 14C in Urine Following Oral Administration (%14C_Urine_PO) of Radiolabeled PF-06865571 in Period 1
timeFrame: Period 1: up to 48 hours post-dose (Day 1 to Day 3)
measure: Percentage of Total 14C in Urine Following IV Microtracer Administration (%14C_Urine_IV) of Radiolabeled PF-06865571 in Period 2
timeFrame: Period 2: up to 48 hours post-dose (Day 1 to Day 3)
measure: Fraction Absorbed (Fa) for Percentage of Excretion of Total 14C in Urine for Oral and IV Radiolabeled PF-06865571
timeFrame: Period 1 and Period 2: up to 48 hours post-dose (Day 1 to Day 3)
Other outcomes:
Locations:
city: Madison
country: United States
facility: Labcorp Clinical Research Unit
state: Wisconsin
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: