The purpose of this study is to learn about how much PF-07220060 will be taken up and processed by healthy male participants. The study is seeking for participants who: * are males aged 18 to 65 years and are healthy. * have Body mass index (BMI) between 17.5 and 30.5 kilograms/meter2 * have a total body weight of at least 50 kilograms. The study consists of two groups. In group 1, participants will take one amount of PF-07220060 by mouth. In group 2, participants will take one amount by mouth and one amount as an injection through a vein at the study clinic. In group 1, participants will stay at the clinic site for up to 15 days. In group 2, the duration of participants' stay depends on the results of group 1. 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-07220060 in participants' blood, urine, and feces samples. This will help to know how much the study medicine is getting taken up 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 9 weeks from the screening until the follow-up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
A single oral dose of \[14C\]PF-07220060, will be administered as a liquid formulation in Cohort 1.
A single oral dose of PF-07220060, will be administered as a liquid formulation in Cohort 2.
A single IV infusion of \[14C\]PF-07220060 will be administered in Cohort 2 at Tmax after the administration of the unlabeled oral dose.
PRA Health Sciences
Groningen, Netherlands
Percentage of Total Radiocarbon (14C) Excreted in Urine
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.
Time frame: From Predose up to 14 days post-dose
Percentage of Total Radiocarbon (14C) Excreted in Feces: Cohort 1
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.
Time frame: From Predose up to 14 days post-dose
Cumulative Percent Recovery of Total Radiocarbon (14C)
Percentage recovery of total radioactivity (14C ) in urine and feces was determined based on total administered dose.
Time frame: From Predose up to 14 days post-dose
Percentage of Metabolite Detected in Plasma After Oral Administration of PF-07220060: Cohort 1
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.
Time frame: From Predose up to 96 hours post-dose
Percentage of Metabolite Detected in Urine After Oral Administration of PF-07220060: Cohort 1
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.
Time frame: From Predose up to 144 hours post-dose
Percentage of Metabolite Detected in Feces After Oral Administration of PF-07220060: Cohort 1
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.
Time frame: From Predose up to 196 hours post-dose
Percentage of Metabolite Detected in Feces After IV Administration of PF-07220060: Cohort 2
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.
Time frame: From Predose up to 196 hours post-dose
Absolute Oral Bioavailability for Plasma Dose-Normalized Area Under the Curve (AUC)Infinity: Cohort 2
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.
Time frame: From Predose up to 14 days post-dose
Cohort 1 and 2: Fraction of PF-07220060 Dose Absorbed (Fa)
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.
Time frame: From Predose up to 14 days post-dose
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: Baseline up to 35 days after the last dose of study intervention (up to Day 36)
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Baseline up to 35 days after the last dose of study intervention (up to Day 36)
Number of Participants With Clinically Significant Abnormalities in Vital Signs
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.
Time frame: Baseline up to 35 days after the last dose of study intervention (up to Day 36)
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
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.
Time frame: Baseline up to 35 days after the last dose of study intervention (up to Day 36)