A Study to Understand How the Study Medicine (PF-07081532) is Processed and Eliminated in Healthy Men

A PHASE 1, OPEN-LABEL, 2-PERIOD, FIXED SEQUENCE STUDY TO INVESTIGATE THE ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF [14C]PF-07081532 AND TO ASSESS THE ABSOLUTE BIOAVAILABILITY AND FRACTION ABSORBED OF PF-07081532 IN HEALTHY MALE PARTICIPANTS USING A [14C]-MICROTRACER APPROACH

The purpose of this clinical trial is to learn about how much PF-07081532 will be taken up and processed by healthy male participants. The study consists of two parts, called study periods. In Period 1, participants will take one dose of PF-07081532 by mouth. In Period 2, participants will take one dose by mouth and one dose as an injection through a vein at the study clinic.

In Period 1, participants will stay at the clinic site for up to 21 days. In Period 2, they will stay at the clinic site for 7 days. During their stays, participants will have their blood, urine, and feces collected by the study doctors several times. We will measure the level of PF-07081532 in participants' blood, urine, and feces samples. This will help us know how much the study medicine is getting taken in by the body. At the end of the study, participants will be contacted by phone to check in. Participants will be involved in this study for about 12 weeks.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Oral [14C]PF-07081532; Drug: Oral PF-07081532 and IV [14C]PF-07081532

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

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • PRA Health Sciences

Participation Criteria

Eligibility Criteria

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

Description

Key Eligibility criteria for this study include, but are not limited to the following:

Inclusion criteria:

Healthy Male participants must be 18 to 60 years of age, inclusive.

Overtly healthy as determined by medical evaluation including medical history, physical examination, blood pressure and pulse rate measurement, standard 12-lead ECG, and laboratory tests.

BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures

Exclusion criteria:

History of irregular bowel movements (eg, irritable bowel syndrome, frequent episodes of diarrhea, or constipation defined by less than 1 bowel movement on average per 2 days) or lactose intolerance

Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).

Previous administration with an investigational product (drug or vaccine) within 90 days (or as determined by the local requirement) preceding the first dose of study intervention used in this study.

Total 14C radioactivity measured in plasma exceeding 11 mBq/mL.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: One group of healthy adult male participants

Drug: Oral [14C]PF-07081532; A single oral dose of [14C]PF-07081532, will be administered as a liquid formulation in study period 1.; Drug: Oral PF-07081532 and IV [14C]PF-07081532; In study period 2: a single, oral, unlabeled dose of PF-07081532 will be administered as a liquid formulation. Approximately 1 hours after the administration of the unlabeled oral dose, a single dose of [14C]PF-07081532 will be administered via intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total recovery of radioactivity in urine, feces, and emesis (if any), and both routes combined, expressed as a percent of total oral radioactive dose administered.	To characterize the extent of excretion of total radioactivity in urine, feces, and emesis (if any) following administration of a single oral dose of [14C]PF-07081532.	Period 1 Pre-dose to maximum Day 21
Amount of metabolites of [14C]PF-07081532 in plasma, urine, and feces.	To characterize the metabolic profile and identify circulating and excreted metabolites following administration of a single oral dose of [14C]PF-07081532.	0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144-480 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClast of oral radiolabeled PF-07081532 in plasma	Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast) of radiolabeled PF-07081532 following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post-dose
Cmax of oral radiolabeled PF-07081532 in plasma	Maximum plasma concentration of radiolabeled PF-07081532 following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post-dose
Tmax of oral radiolabeled PF-07081532 in plasma	Time to Cmax of radiolabeled PF-07081532 following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post-dose
AUCinf of oral radiolabeled PF-07081532 in plasma (if data permit)	Area under the plasma concentration-time profile from time zero extrapolated to infinite time following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post-dose
t1/2 of oral radiolabeled PF-07081532 in plasma (if data permit)	Terminal elimination half-life following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post-dose
AUClast of total radioactivity in plasma	Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast) of total radioactivity following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144-480 hours post-dose
Cmax of total radioactivity in plasma	Maximum plasma concentration of total radioactivity following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144-480 hours post-dose
Tmax of total radioactivity in plasma	Time to Cmax of total radioactivity following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144-480 hours post-dose
AUCinf of total radioactivity in plasma (if data permit)	Area under the plasma total radioactivity concentration-time profile from time zero extrapolated to infinite time following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144-480 hours post-dose
t1/2 of total radioactivity in plasma (if data permit)	Terminal elimination half-life following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144-480 hours post-dose
CL/F of oral radiolabeled PF-07081532 in plasma (if data permit)	Apparent clearance following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post-dose
Vz/F of oral radiolabeled PF-07081532 in plasma (if data permit)	Apparent volume of distribution following administration of a single oral dose of radiolabeled PF-07081532.	Period 1: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post-dose
AUClast of intravenous radiolabeled PF-07081532 in plasma	Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast) of radiolabeled PF-07081532 following administration of a single intravenous dose of radiolabeled PF-07081532.	Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
Dose normalized AUClast of intravenous radiolabeled PF-07081532 in plasma	Dose normalized area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast) of radiolabeled PF-07081532 following administration of a single intravenous dose of radiolabeled PF-07081532.	Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
Cmax of intravenous radiolabeled PF-07081532 in plasma	Maximum plasma concentration of radiolabeled PF-07081532 following administration of a single intravenous dose of radiolabeled PF-07081532.	Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
Dose normalized Cmax of intravenous radiolabeled PF-07081532 in plasma	Dose normalized maximum plasma concentration of radiolabeled PF-07081532 following administration of a single intravenous dose of radiolabeled PF-07081532.	Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
Tmax of intravenous radiolabeled PF-07081532 in plasma	Time to Cmax of radiolabeled PF-07081532 following administration of a single intravenous dose of radiolabeled PF-07081532.	Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
AUCinf of intravenous radiolabeled PF-07081532 in plasma (if data permit)	Area under the plasma concentration-time profile from time zero extrapolated to infinite time following administration of a single intravenous dose of radiolabeled PF-07081532.	Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
Dose normalized AUCinf of intravenous radiolabeled PF-07081532 in plasma (if data permit)	Dose normalized area under the plasma concentration-time profile from time zero extrapolated to infinite time following administration of a single intravenous dose of radiolabeled PF-07081532.	Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
t1/2 of intravenous radiolabeled PF-07081532 in plasma (if data permit)	Terminal elimination half-life following administration of a single intravenous dose of radiolabeled PF-07081532.	Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
CL of intravenous radiolabeled PF-07081532 in plasma (if data permit)	Systemic clearance following administration of a single intravenous dose of radiolabeled PF-07081532.	Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
Vss of intravenous radiolabeled PF-07081532 in plasma (if data permit)	Steady-state volume of distribution following administration of a single intravenous dose of radiolabeled PF-07081532.	Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
Mean residence Time (MRT) of intravenous radiolabeled PF-07081532 in plasma (if data permit)		Period 2: Pre-dose, 0.17, 0.25, 0.33, 0.5, 1, 3, 5, 7, 9, 11, 14, 23, 35, 47, 71, 95, 119, 143 hours post-dose
Absolute oral bioavailability (F) of PF-07081532	Dose-normalized plasma AUCinf (if data permit, otherwise AUClast) following oral unlabeled PF-07081532 compared to IV microtracer PF-07081532 in Period 2.	Period 2: Pre-dose up to 144 hours post-dose
Fraction of the dose absorbed (Fa) for oral PF-07081532	Total urinary radioactivity following oral administration of radiolabeled PF-07081532 in Period 1 and IV microtracer administration of PF-07081532 in Period 2.	Period 2: Pre-dose up to 144 hours post-dose
Number of participants with treatment emergent clinically significant laboratory abnormalities		Baseline, day 7-21 of period 1, baseline, day 7 of period 2
Number of participants with treatment emergent clinically significant abnormal ECG measurements		Pre-dose, day 7-21 of period 1, Pre-dose, day 7 of period 2
Number of participants with treatment emergent clinically significant abnormal vital measurements		Pre-dose, day 7-21 of period 1, Pre-dose, day 7 of period 2
Number of participants with adverse events		Pre-dose, day 7-21 of period 1, Pre-dose, day 7 of period 2

Collaborators and Investigators

• Sponsor: 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): December 21, 2022
• Primary Completion (Actual): March 15, 2023
• Study Completion (Actual): March 15, 2023

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Bioavailability; Distribution; Absorption; Metabolism; Elimination; Mass balance; Fraction absorbed; Healthy Males
• Other Study ID Numbers: C3991006

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
• product manufactured in and exported from the U.S.: Yes