Healthy Participants
Conditions
Keywords
Absorption, Distribution, Metabolism, Elimination, ADME (Absorption, Distribution, Metabolism and Excretion), Pharmacokinetics, Bioavailability, Fraction absorbed, Mass balance, Healthy Males, Cyclin-Dependent Kinase 4 (CDK4) inhibitor
Brief summary
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.
Interventions
DRUGOral [14C]PF-07220060
A single oral dose of \[14C\]PF-07220060, will be administered as a liquid formulation in Cohort 1.
DRUGOral PF-07220060
A single oral dose of PF-07220060, will be administered as a liquid formulation in Cohort 2.
DRUGIV [14C] PF-07220060
A single IV infusion of \[14C\]PF-07220060 will be administered in Cohort 2 at Tmax after the administration of the unlabeled oral dose.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Key Eligibility criteria for this study include, but are not limited to the following: Inclusion Criteria: * Male participants aged 18 to 65 years at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. * Body mass index (BMI) of 17.5-30.5 kg/m2; and a total body weight \>50 kg (110 lb). * Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
Exclusion criteria
* Participants with a history of irregular bowel movements (eg, regular episodes of diarrhea or constipation, irritable bowel syndrome \[IBS\] or lactose intolerance). * Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives (whichever is longer) preceding the first dose of study intervention used in this study. Previous exposure to PF-07220060 or participation in studies requiring PF-07220060 administration. * Total 14C radioactivity measured in plasma exceeding 11 mBq/mL.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Total Radiocarbon (14C) Excreted in Urine | From Predose up to 14 days post-dose | 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 Total Radiocarbon (14C) Excreted in Feces: Cohort 1 | From Predose up to 14 days post-dose | 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. |
| Cumulative Percent Recovery of Total Radiocarbon (14C) | From Predose up to 14 days post-dose | Percentage recovery of total radioactivity (14C ) in urine and feces was determined based on total administered dose. |
| Percentage of Metabolite Detected in Plasma After Oral Administration of PF-07220060: Cohort 1 | From Predose up to 96 hours post-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. |
| Percentage of Metabolite Detected in Urine After Oral Administration of PF-07220060: Cohort 1 | From Predose up to 144 hours post-dose | 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. |
| Percentage of Metabolite Detected in Feces After Oral Administration of PF-07220060: Cohort 1 | From Predose up to 196 hours post-dose | 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. |
| Percentage of Metabolite Detected in Feces After IV Administration of PF-07220060: Cohort 2 | From Predose up to 196 hours post-dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Oral Bioavailability for Plasma Dose-Normalized Area Under the Curve (AUC)Infinity: Cohort 2 | From Predose up to 14 days post-dose | 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. |
| Cohort 1 and 2: Fraction of PF-07220060 Dose Absorbed (Fa) | From Predose up to 14 days post-dose | 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Baseline up to 35 days after the last dose of study intervention (up to Day 36) | 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. |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | Baseline up to 35 days after the last dose of study intervention (up to Day 36) | 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. |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs | Baseline up to 35 days after the last dose of study intervention (up to Day 36) | 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. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Baseline up to 35 days after the last dose of study intervention (up to Day 36) | 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. |
Countries
Netherlands
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 44.5 Years STANDARD_DEVIATION 20.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
None listed