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

Pfizer5 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

PF-07304814DRUG

PF-07304814 is an anti-viral, formulated for intravenous delivery

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Fortrea Clinical Research Unit - Madison

Madison, Wisconsin, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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).

Time frame: 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]

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 24 hours post the start of infusion

C24 for Plasma Total [14C]

Obsereved plasma concentration at 24 hours. This was observed directly from data.

Time frame: 24hours post the start of infusion

Systematic Clearance (CL) for Plasma PF-07304814

Systemic clearance. This was determined by Dose/AUCinf (if data permit).

Time frame: 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.

Time frame: 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).

Time frame: 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]

Time frame: pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion

Secondary Outcomes

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).

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: From Screening (Day-42 to Day-2) to 216h or early termination/discontinuation