Study to Investigate the Mass Balance, Metabolism, and Excretion of [14C]-PF-07304814 in Healthy Participants

A PHASE 1, OPEN-LABEL, SINGLE-DOSE STUDY TO INVESTIGATE THE MASS BALANCE, METABOLISM AND EXCRETION OF [14C]-PF-07304814 IN HEALTHY PARTICIPANTS USING A 14C-MICROTRACER APPROACH

This open-label, single dose study in approximately 5 healthy male and female (of non childbearing potential only) participants has been designed to characterize mass balance and further the understanding of human pharmacokinetics, metabolism, and excretion of PF 07304814 administered at a dose of 500 mg [14C] PF-07304814 containing approximately 420 nCi [14C] PF-07304814 as a constant-rate, continuous IV infusion over 24 hours

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-07304814

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Fortrea Clinical Research Unit - Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male and female participants must be 18 to 55 years of age, inclusive, at the time of signing the ICD.
2. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECGs.
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
4. BMI of 18 to 32 kg/m2; and a total body weight >50 kg (110 lb).

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
2. Positive test result for SARS-CoV-2 infection at the time of Screening or Day -1.
3. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.
4. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).
5. Participants who have received a COVID-19 vaccine within the past 2 weeks; and/or participants who are scheduled to receive a second COVID-19 vaccination dose during the in-clinical period of this study.
6. A positive urine drug test.
7. Total 14C radioactivity measured in plasma exceeding 11 mBq/mL at "Screening" .
8. Females who are breastfeeding.
9. History of tobacco or nicotine use within 3 months prior to dosing, or a positive cotinine at screening or Day -1.
10. Participants enrolled in a previous radionucleotide study or who have received radiotherapy within 12 months prior to screening or such that total radioactivity would exceed acceptable dosimetry (ie, occupational exposure of 5 rem per year).

13. Participants whose occupation requires exposure to radiation or monitoring of radiation exposure.

14. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: PF-07304814; PF-07304814 is an anti-viral, formulated for intravenous delivery	Drug: PF-07304814; PF-07304814 is an anti-viral, formulated for intravenous delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Mean (SD) Amount of [14C] Recovered in Urine, as a Percent of the Total [14C] Dose Administered	This is to confirm mass balance and characterize the routes of elimination of [14C]-PF-07304814 and drug related materials following 420 nCi/500 mg dose of [14C] PF-07304814.	from pre-dose to 216h post the start of infusion
The Mean (SD) Amount of [14C] Recovered in Feces, as a Percent of the Total [14C] Dose Administered	This is to confirm mass balance and characterize the routes of elimination of [14C]-PF-07304814 and drug related materials following 420 nCi/500 mg dose of [14C] PF-07304814.	from pre-dose to 216h post the start of infusion
The Mean (SD) Percentage of [14C] Relative to the Administered Dose in Excreta (Urine + Feces)	This is to confirm mass balance and characterize the routes of elimination of [14C]-PF-07304814 and drug related materials following 420 nCi/500 mg dose of [14C] PF-07304814.	from pre-dose to 216h post the start of infusion
Area Under the Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for Plasma PF-07304814 and Plasma PF-00835231	Area under the concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), using linear/log trapezoidal method.	0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Area Under the Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for Plasma Total [14C]	Area under the concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), using linear/log trapezoidal method.	pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Area Under the Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for Plasma PF-00835231	Area under the concentration-time profile from time zero extrapolated to infinite time. AUClast + (Clast*/kel), where Clast* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis (if data permit).	0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
AUCinf for Plasma Total [14C]	Area under the concentration-time profile from time zero extrapolated to infinite time. AUClast + (Clast*/kel), where Clast* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis (if data permit).	pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Maximum Observed Plasma Concentration (Cmax) for Plasma PF-07304814 and Plasma PF-00835231	Maximum observed plasma concentration. This was observed directly from data.	0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Cmax for Plasma Total [14C]	Maximum observed plasma concentration. This was observed directly from data.	pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Time for Cmax (Tmax) for Plasma PF-07304814 and Plasma PF-00835231	Time for Cmax. This was observed directly from data as time of first occurrence.	pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Tmax for Plasma Total 14C	Time for Cmax. This was observed directly from data as time of first occurrence.	pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Obsereved Plasma Concentration at 24 Hours (C24) for Plasma PF-07304814 and Plasma PF-00835231	Obsereved plasma concentration at 24 hours. This was observed directly from data.	24 hours post the start of infusion
C24 for Plasma Total [14C]	Obsereved plasma concentration at 24 hours. This was observed directly from data.	24hours post the start of infusion
Systematic Clearance (CL) for Plasma PF-07304814	Systemic clearance. This was determined by Dose/AUCinf (if data permit).	0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Steady-state Volume of Distribution Following Intravenous Infusion (Vss) for Plasma PF-07304814	Steady-state volume of distribution following intravenous infusion. This was determined by Vss=CL × [MRT-(infusion time/2)] where MRT is the Mean Residence Time and is calculated as AUMCinf (the area under the first moment curve from time 0 extrapolated to infinite time)/AUCinf (area under the concentration-time profile from time 0 extrapolated to infinite time), if data permit.	0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Terminal Elimination Half-life (t½) for Plasma PF-00835231	Terminal elimination half-life. This was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve (if data permit).	0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
t½ for Plasma Total [14C]	Terminal elimination half-life. This was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve (if data permit).	pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Total Radioactivity in Each Matrix (Plasma, Urine and Feces) of Metabolites of PF-07304814	The percentage of radioactivity collected over the time frame for each metabolite was determined and reported as percentage of total radioactivity in each matrix (plasma, urine and feces).	Predose to maximum of Day 10
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	Treatment-Emergent Adverse Event if the event started during the effective duration of treatment. All events that start on or after the first dosing day and time/ start time, if collected, but before the last dose plus the lag time (28 days) will be flagged as TEAEs. A serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent or significant disability/incapacity, 5. was a congenital anomaly/birth defect, 6. was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic, is considered serious, and other situations defined in the protocol	From first dose up to 28-35 days from administration of the dose of study intervention (maximum of 35 days)
Number of Subjects With Vital Signs Data Meeting Categorical Summarization Criteria	The following abnormality criteria were applied: diastolic blood pressure: value < 50 mmHg, change >=20 mmHg increase/decrease; systolic blood pressure: value < 90 mmHg, change >= 30 mmHg increase/decrease; pulse rate: value< 40 beats per minute, value > 120 beats per minute.	from Screening (Day-42 to Day-2) to 216h or early termination/discontinuation
Number of Subjects With Laboratory Test Abnormalities (Without Regards to Baseline Abnormality)	Safety laboratory assessments including urinalysis, hematology, and chemistry were performed at the indicated time-points. All the safety laboratory samples must be collected following at least a 4 hour fast.	From Screening (Day-42 to Day-2) to 216h or early termination/discontinuation
Number of Subjects With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria	ECG endpoints meeting the criteria of potential clinical concern were summarized by treatment using categories as defined:PR interval (msec): value >280, %change >= 25%, %change >= 50%; QRS complex (msec): value > 120; QT interval (msec): value > 500; QTcF (msec): 450 < value <=480, 480 <value <= 500, 30 <= increase <= 60, increase >60.	From Screening (Day-42 to Day-2) to 216h or early termination/discontinuation

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): October 7, 2021
• Primary Completion (Actual): December 10, 2021
• Study Completion (Actual): December 10, 2021

Study Registration Dates

• First Submitted: September 10, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (Actual): September 20, 2021

Study Record Updates

• Last Update Posted (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 13, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: COVID-19; SARS-COV-2; Viral Disease
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Virus Diseases; lufotrelvir
• Other Study ID Numbers: C4611003; NCT05050682 (Registry Identifier: ClinicalTrials.gov)

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