A Study in Healthy Adult Male Participants to Assess Absorption, Distribution, Metabolism and Excretion (ADME) of Radiolabeled PF-06865571.

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Oral [14C]PF-06865571; Drug: Oral PF-06865571; Drug: IV [14C]PF-06865571

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

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Labcorp Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study arm; One arm of healthy male participants administered a single oral dose of [14C]PF-06865571; followed by a single dose of unlabeled PF-06865571, and IV administration of [14C]PF-06865571 three hours later.	Drug: Oral [14C]PF-06865571; Oral radiolabeled PF-06865571; Drug: Oral PF-06865571; Oral PF-06865571; Drug: IV [14C]PF-06865571; IV radiolabeled PF-06865571

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Recovery of Radioactivity in Urine as Percentage of Total Radioactive Dose of PF-06865571 Administered	The total recovery of radioactivity in urine was listed and summarized using descriptive statistics. In this outcome measure, the percentages of dose excreted in urine in Period 1 and Period 2 were reported.	Period 1: Day -1 to maximum Day 21; Period 2: Day 1 to maximum Day 3
Total Recovery of Radioactivity in Feces as Percentage of Total Radioactive Dose of PF-06865571 Administered	The total recovery of radioactivity in feces was listed and summarized using descriptive statistics. In this outcome measure, the percentages of dose excreted in feces in Period 1 and Period 2 were reported.	Period 1: Day -1 to maximum Day 21; Period 2: Day 1 to maximum Day 3
Total Recovery of Radioactivity in Total Excreta (Urine + Feces) as Percentage of Total Radioactive Dose of PF-06865571 Administered	The total recovery of radioactivity in the combination of urine and feces was listed and summarized using descriptive statistics. In this outcome measure, the percentages of dose excreted in total excreta (urine + feces) in Period 1 and Period 2 were reported.	Period 1: Day -1 to maximum Day 21; Period 2: Day 1 to maximum Day 3
Relative Abundance (Mean Value) of Radiolabeled PF-06865571 in Plasma in Period 1	Plasma samples were analyzed for radiolabeled PF-06865571 and its metabolites. [14C]PF-06865571 and the major metabolites in plasma, after oral administration of 300 mg [14C]PF-06865571 were identified. In this outcome measure, relative abundance of radiolabeled PF-06865571 in plasma based on [14C] quantitation was reported. The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.	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)
Relative Abundance (Mean Value) of Metabolites of Radiolabeled PF-06865571 in Plasma in Period 1	Plasma samples were analyzed for radiolabeled PF-06865571 and its metabolites. [14C]PF-06865571 and the major metabolites in plasma, after oral administration of 300 mg [14C]PF-06865571 were identified. In this outcome measure, relative abundance of the metabolites of [14C]PF-06865571 in plasma based on [14C] quantitation was reported. The metabolites included 487, 391, 412, 556, M6 (PF-07822633), M7 (PF-07911964), 584, M1 (PF-06878236), 426, M4 (PF-06887477), 600, M5 (PF-06885984) and M2 (PF-06868609). The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.	Period 1: 0, 0.5, 3, 6, 12, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
Relative Abundance (Mean Value) of Radiolabeled PF-06865571 in Urine in Period 1	Urine samples were analyzed for radiolabeled PF-06865571 and its metabolites. [14C]PF-06865571 and the major metabolites in urine, after oral administration of 300 mg [14C]PF-06865571 were identified. In this outcome measure, relative abundance of radiolabeled PF-06865571 in urine based on [14C] quantitation was reported. The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.	Period 1: Day -1 to maximum Day 21
Relative Abundance (Mean Value) of Metabolites of Radiolabeled PF-06865571 in Urine in Period 1	Urine samples were analyzed for radiolabeled PF-06865571 and its metabolites. [14C]PF-06865571 and the major metabolites in urine, after oral administration of 300 mg [14C]PF-06865571 were identified. In this outcome measure, relative abundance of the metabolites of [14C]PF-06865571 in urine based on [14C] quantitation was reported. The metabolites included 487, 391, 412, 556, M6 (PF-07822633), M7 (PF-07911964), 584, M1 (PF-06878236), 426, M4 (PF-06887477), 600, M5 (PF-06885984) and M2 (PF-06868609). The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.	Period 1: Day -1 to maximum Day 21
Relative Abundance (Mean Value) of Radiolabeled PF-06865571 in Feces in Period 1	Fecal samples were analyzed for radiolabeled PF-06865571 and its metabolites. [14C]PF-06865571 and the major metabolites in feces, after oral administration of 300 mg [14C]PF-06865571 were identified. In this outcome measure, relative abundance of radiolabeled PF-06865571 in feces based on [14C] quantitation was reported. The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.	Period 1: Day -1 to maximum Day 21
Relative Abundance (Mean Value) of Metabolites of Radiolabeled PF-06865571 in Feces in Period 1	Fecal samples were analyzed for radiolabeled PF-06865571 and its metabolites. [14C]PF-06865571 and the major metabolites in feces, after oral administration of 300 mg [14C]PF-06865571 were identified. In this outcome measure, relative abundance of the metabolites of [14C]PF-06865571 in feces based on [14C] quantitation was reported. The metabolites included 487, 391, 412, 556, M6 (PF-07822633), M7 (PF-07911964), 584, M1 (PF-06878236), 426, M4 (PF-06887477), 600, M5 (PF-06885984) and M2 (PF-06868609). The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.	Period 1: Day -1 to maximum Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	AUClast is defined as area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast). The determination method of AUClast was linear/log trapezoidal rule.	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)
Maximum Plasma Concentration (Cmax) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1	Cmax is defined as maximum plasma concentration. The determination method of Cmax was observing directly from data.	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)
Time for Cmax (Tmax) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1	Tmax is defined as time to reach maximum observed plasma concentration. The determination method of Tmax was observing directly from data as time of first occurrence.	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)
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	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). The determination method of AUCinf was AUClast + (Clast*/ kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel was the terminal phase rate constant.	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)
Terminal Elimination Half-life (t1/2) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1	Terminal elimination half-life (t1/2) was the time measured for the plasma concentration to decrease by one half. The determination method of t1/2 was loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	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)
AUClast of Oral PF-06865571 in Plasma in Period 1	AUClast is defined as area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast). The determination method of AUClast was linear/log trapezoidal rule.	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)
Cmax of Oral PF-06865571 in Plasma in Period 1	Cmax is defined as maximum plasma concentration. The determination method of Cmax was observing directly from data.	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)
Tmax of Oral PF-06865571 in Plasma in Period 1	Tmax is defined as time to reach maximum observed plasma concentration. The determination method of Tmax was observing directly from data as time of first occurrence.	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)
AUCinf of Oral PF-06865571 in Plasma in Period 1	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). The determination method of AUCinf was AUClast + (Clast*/ kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel was the terminal phase rate constant.	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)
t1/2 of Oral PF-06865571 in Plasma in Period 1	Terminal elimination half-life (t1/2) was the time measured for the plasma concentration to decrease by one half. The determination method of t1/2 was loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	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)
AUClast of Intravenous (IV) Radiolabeled PF-06865571 in Plasma in Period 2	AUClast is defined as area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast). The determination method of AUClast was linear/log trapezoidal rule.	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)
Cmax of IV Radiolabeled PF-06865571 in Plasma in Period 2	Cmax is defined as maximum plasma concentration. The determination method of Cmax was observing directly from data.	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)
Tmax of IV Radiolabeled PF-06865571 in Plasma in Period 2	Tmax is defined as time to reach maximum observed plasma concentration. The determination method of Tmax was observing directly from data as time of first occurrence.	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)
t1/2 of IV Radiolabeled PF-06865571 in Plasma in Period 2	Terminal elimination half-life (t1/2) was the time measured for the plasma concentration to decrease by one half. The determination method of t1/2 was loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	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)
AUCinf of IV Radiolabeled PF-06865571 in Plasma in Period 2	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). The determination method of AUCinf was AUClast + (Clast*/ kel), where Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel was the terminal phase rate constant.	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)
Systemic Clearance (CL) of IV Radiolabeled PF-06865571 in Plasma in Period 2	CL is a quantitative measure of the rate at which a drug substance is removed from the body. The determination method of CL was dose/AUCinf.	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)
Steady State Volume of Distribution (Vss) of IV Radiolabeled PF-06865571 in Plasma in Period 2	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. Vss is the apparent volume of distribution at steady-state.	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)
Dose-Normalized AUCinf (AUCinf[dn]) of Oral Unlabeled PF-06865571 in Plasma in Period 2	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). AUCinf(dn) is defined as dose normalized (to 1 mg equivalent) AUCinf, which equals to AUCinf/Dose.	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)
AUCinf(dn) of IV Microtracer of Radiolabeled PF-06865571 in Plasma in Period 2	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). AUCinf(dn) is defined as dose normalized (to 1 mg equivalent) AUCinf, which equals to AUCinf/Dose.	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)
Absolute Oral Bioavailability (F) of Oral Unlabeled and IV Radiolabeled PF-06865571 for Plasma AUCinf(dn) in Period 2	Absolute Oral Bioavailability (F) provided information on the amount of PF-06865571 reaching the systemic circulation. F was estimated as the ratio of adjusted geometric means of dose-normalized AUCinf for oral unlabeled PF-06865571 and IV labeled 14C PF-06865571 in plasma (from Period 2 only) which was equivalent to the following equation: F = [PF-06865571_AUCpo/[14C]PF-06865571_AUCiv]×[ [14C]PF-06865571_Doseiv/ PF-06865571_Dosepo], where PF-06865571_AUCpo = AUCinf(dn) of oral unlabeled PF-06865571, [14C]PF-06865571_AUCiv = AUCinf(dn) of intravenous radiolabeled PF-06865571, [14C]PF-06865571_Doseiv = dose of intravenous radiolabeled PF-06865571, PF-06865571_Dosepo = dose of oral unlabeled PF-06865571.	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)
Percentage of Total 14C in Urine Following Oral Administration (%14C_Urine_PO) of Radiolabeled PF-06865571 in Period 1	%14C_Urine_PO is defined as percentage of the radioactive dose administered that is excreted in the urine following oral administration. %14C_Urine_PO = Total 14C_Urine_PO/14C Dosepo × 100, where PO = orally, Total 14C_Urine_PO = total radioactivity excreted into the urine post-dose following oral administration of [14C]PF-06865571, 14C Dosepo = dose of 14C following oral administration of [14C]PF-06865571.	Period 1: up to 48 hours post-dose (Day 1 to Day 3)
Percentage of Total 14C in Urine Following IV Microtracer Administration (%14C_Urine_IV) of Radiolabeled PF-06865571 in Period 2	%14C_Urine_IV is defined as percentage of the radioactive dose administered that is excreted in the urine following IV administration. %14C_Urine_IV = Total 14C _Urine_IV/14C Doseiv × 100, where IV = intravenous, Total 14C_Urine_IV = total radioactivity excreted into the urine following IV administration of [14C]PF 06865571, 14C Doseiv = dose of 14C following IV administration of [14C]PF 06865571.	Period 2: up to 48 hours post-dose (Day 1 to Day 3)
Fraction Absorbed (Fa) for Percentage of Excretion of Total 14C in Urine for Oral and IV Radiolabeled PF-06865571	Determination of the Fraction Absorbed (Fa) (obtained from Periods 1 and 2) provided information on the fraction of the total PF-06865571 dose absorbed, regardless of the fate of that dose after absorption (ie, metabolism, degradation, etc). Fa was estimated as the ratio of the adjusted geometric means of % of administered radioactive dose excreted into the urine following oral and IV administration of [14C]PF-06865571 microtracer dose over the same collection time (up to 48 hours post dose) in Periods 1 and 2, respectively: Fa = [% 14C_Urine_PO/% 14C_Urine_IV].	Period 1 and Period 2: up to 48 hours post-dose (Day 1 to Day 3)

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 (Actual): May 11, 2021
• Primary Completion (Actual): July 11, 2021
• Study Completion (Actual): August 6, 2021

Study Registration Dates

• First Submitted: April 19, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: ADME
• Other Study ID Numbers: C2541007

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