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

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

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces. Data could not be estimated for AUCinf for the phosphate prodrug PF-07304814 due to the lack of a well characterized terminal elimination phase. A well characterized terminal phase is defined as one with at least 3 data points can be used for log-linear regression, r2 ≥0.9, and AUCextrap% ≤ 20%.

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

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces.

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

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces.

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

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces. AUCinf values were not reported for the total \[14C\] due to the lack of a well characterized terminal elimination phase. A well characterized terminal phase is defined as one with at least 3 data points can be used for log-linear regression, r2 ≥0.9, and AUCextrap% ≤ 20%.

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

Time frame: 24hours post the start of infusion

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces.

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

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces.

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

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces.

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

Time frame: 24 hours post the start of infusion

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces.

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

Population: The PK parameter analysis population is defined as all participants randomized and treated who have at least 1 of the parameters of primary interest in plasma, urine or feces. Vss values were not reported for the phosphate prodrug PF-07304814 due to the lack of a well characterized terminal elimination phase. A well characterized terminal phase is defined as one with at least 3 data points can be used for log-linear regression, r2 ≥0.9, and AUCextrap% ≤ 20%.

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

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces. CL values were not reported for the phosphate prodrug PF-07304814 due to the lack of a well characterized terminal elimination phase. A well characterized terminal phase is defined as one with at least 3 data points can be used for log-linear regression, r2 ≥0.9, and AUCextrap% ≤ 20%.

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

Population: The PK parameter analysis population is defined as all participants randomized and treated who have at least 1 of the parameters of primary interest in plasma, urine or feces. t½ values were not reported for the total \[14C\] due to the lack of a well characterized terminal elimination phase.

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

Population: The PK parameter analysis population is defined as all participants randomized and treated who have at least 1 of the parameters of primary interest in plasma, urine or feces. Data could not be estimated for t½ for the phosphate prodrug PF-07304814 due to the lack of a well characterized terminal elimination phase. A well characterized terminal phase is defined as one with at least 3 data points can be used for log-linear regression, r2 ≥0.9, and AUCextrap% ≤ 20%.

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

Population: Mass Balance Analysis Set: The mass balance analysis set was defined as all participants who received study intervention and who had evaluable total \[14C\] concentration (urinary and fecal) data and who had no protocol deviations or AEs (such as diarrhea or severe constipation) that might have affected the mass balance analysis.

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

Population: Mass Balance Analysis Set: The mass balance analysis set was defined as all participants who received study intervention and who had evaluable total \[14C\] concentration (urinary and fecal) data and who had no protocol deviations or AEs (such as diarrhea or severe constipation) that might have affected the mass balance analysis.

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

Population: Mass Balance Analysis Set: The mass balance analysis set was defined as all participants who received study intervention and who had evaluable total \[14C\] concentration (urinary and fecal) data and who had no protocol deviations or AEs (such as diarrhea or severe constipation) that might have affected the mass balance analysis.

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

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces.

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

Population: The PK parameter analysis population was defined as all participants randomized and treated who had at least 1 of the parameters of primary interest in plasma, urine or feces.

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

Population: All participants assigned to study intervention and who take at least 1 dose of study intervention.

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

Population: All participants assigned to study intervention and who take at least 1 dose of study intervention.

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)

Population: The safety analysis set includes all participants assigned to study intervention and who take at least 1 dose of study intervention.

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

Population: All participants assigned to study intervention and who take at least 1 dose of study intervention.

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

Population: The PK parameter analysis population is defined as all participants randomized and treated who have at least 1 of the parameters of primary interest in plasma, urine or feces. Data reported with measure type Number as the values reported represent the measured value from a pooled sample from all participants in the study.