Trial Outcomes & Findings for A Study to Understand What the Body Does to the Study Medicine Called PF-07220060 When Taken by Healthy Adults (NCT NCT06267963)

A Study to Understand What the Body Does to the Study Medicine Called PF-07220060 When Taken by Healthy Adults

Percentage of 14C excreted in urine following 14C PF-07220060 dose administration was determined as: (total 14C urine/ 14C dose administered)\*100 where, 14C dose was administered dose of 14C PF-07220060.

Percentage of 14C excreted in feces following 14C PF-07220060 oral dose administration was determined as: (total 14C feces/ 14C oral dose administered)\*100 where, 14C dose was administered dose of 14C PF-07220060.

Percentage recovery of total radioactivity (14C ) in urine and feces was determined based on total administered dose.

The percentage of five major metabolites detected in plasma after oral administration of PF-07220060: 480a, 480b, 496a, M3 and 496b are reported in this outcome measure. The processed samples were analyzed by liquid chromatography mass spectrometry- accelerator mass spectrometry (LC-MS-AMS). For calculation of metabolite percentage of total plasma radioactivity (RA), first composite time-normalized human plasma pools were prepared for each participant from plasma samples collected from 0-96 hours post-dose (i.e., a hamilton pool). Next, a multi-subject pool was created by combining equal volumes of each of the above individual participant pools. Results presented here are the single value output from these individual pooled multi-subject time-normalized samples.

The percentage of five major metabolites detected in urine after oral administration of PF-07220060: 480a, 480b, 496a, M3 and 496b are reported in this outcome measure. The processed samples were analyzed by LC-MS-AMS. For calculation of percentage of metabolites, first composite time-normalized human urine pools were prepared for each participant from urine samples collected from 0-144 hours post-dose (i.e., a hamilton pool). Next, a multi-subject pool was created by combining equal volumes of each of the above individual participant pools. Results presented here are the single value output from these individual pooled multi-subject time-normalized samples.

The percentage of five major metabolites detected in feces after oral administration of PF-07220060: 480a, 480b, 496a, M3 and 496b are reported in this outcome measure. The processed samples were analyzed by LC-MS-AMS. For calculation of percentage of metabolites, first composite time-normalized human fecal homogenate pools were prepared for each participant from fecal samples collected from 0-196 hours post-dose (i.e., a hamilton pool). Next, a multi-subject pool was created by combining equal volumes of each of the above individual participant pools. Results presented here are the single value output from these individual pooled multi-subject time-normalized samples.

The percentage of five major metabolites detected in feces after IV administration of PF-07220060: 480a, 480b, 496a, M3 and 496b are reported in this outcome measure. The processed samples were analyzed by LC-MS-AMS. For calculation of percentage of metabolites, first composite time-normalized human fecal homogenate pools were prepared for each participant from fecal samples collected from 0-196 hours post-dose (i.e., a hamilton pool). Next, a multi-subject pool was created by combining equal volumes of each of the above individual participant pools. Results presented here are the single value output from these individual pooled multi-subject time-normalized samples.

Dose normalized AUCinf (AUCinf\[dn\]) was calculated as AUCinf/Dose, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. Absolute oral bioavailability was defined as the ratio of geometric mean of AUCinf(dn) following orally administered PF-07220060 (i.e., unlabeled PF-07220060) to AUCinf(dn) following intravenously administered \[14C\]PF-07220060 and reported in the statistical analysis section.

Fraction of dose absorbed (Fa) was estimated as the ratio of total radioactivity (dose normalized) excreted into the urine (from time 0 to the time of last measurable concentration) following oral and IV administration of \[14C\]PF-07220060 microtracer doses in cohort 1 and 2, respectively. The total radioactivity excreted in urine following oral and IV administration, expressed as percentage of radioactive dose administered is reported in the descriptive section and fraction of dose absorbed is reported in the statistical analysis section.

An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were defined as any AEs that occurred following start of study intervention and during follow-up within the lag time of up to 35 days after the last dose of study intervention.

Following laboratory parameters were analyzed: clinical chemistry: alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonates, total bilirubin, calcium, chloride, creatinine, cystatin C, estimated glomerular filtration rate (eGFR) serum creatinine, glucose, potassium, protein, sodium, uric acid, blood urea nitrogen. Hematology included basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils, platelets and reticulocyte count. Urinalysis included: glucose, blood, ketones, leukocytes esterase, nitrite, protein and pH. Clinical significance of laboratory abnormalities was determined by investigator.

Vital signs included blood pressure and pulse rate. Blood pressure was measured with the participant in a supine position using an automated device after at least 5 minutes rest for the participant. Clinical significance of vital signs was determined based on investigator's discretion.

Standard 12-lead ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position using an ECG machine that automatically calculated the heart rate and measured PR, QT and, corrected QT interval using Fridericia's formula (QTcF) and QRS interval. Clinical significance of ECG abnormalities was determined based on investigator's discretion.