Healthy Participants
Conditions
Keywords
Absorption, Distribution, Metabolism, Elimination, Bioavailability, Fraction absorbed, Mass balance, Healthy Males
Brief summary
The purpose of this clinical trial is to learn about how much PF-07081532 will be taken up and processed by healthy male participants. The study consists of two parts, called study periods. In Period 1, participants will take one dose of PF-07081532 by mouth. In Period 2, participants will take one dose by mouth and one dose as an injection through a vein at the study clinic. In Period 1, participants will stay at the clinic site for up to 21 days. In Period 2, they will stay at the clinic site for 7 days. 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-07081532 in participants' blood, urine, and feces samples. This will help us know how much the study medicine is getting taken in 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 12 weeks.
Interventions
DRUGOral [14C]PF-07081532
A single oral dose of \[14C\]PF-07081532, will be administered as a liquid formulation in study period 1.
DRUGOral PF-07081532 and IV [14C]PF-07081532
In study period 2: a single, oral, unlabeled dose of PF-07081532 will be administered as a liquid formulation. Approximately 1 hours after the administration of the unlabeled oral dose, a single dose of \[14C\]PF-07081532 will be administered via intravenous infusion.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Key Eligibility criteria for this study include, but are not limited to the following: Inclusion criteria: Healthy Male participants must be 18 to 60 years of age, inclusive. Overtly healthy as determined by medical evaluation including medical history, physical examination, blood pressure and pulse rate measurement, standard 12-lead ECG, and laboratory tests. BMI of 17.5 to 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
History of irregular bowel movements (eg, irritable bowel syndrome, frequent episodes of diarrhea, or constipation defined by less than 1 bowel movement on average per 2 days) or lactose intolerance Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). Previous administration with an investigational product (drug or vaccine) within 90 days (or as determined by the local requirement) preceding the first dose of study intervention used in this study. Total 14C radioactivity measured in plasma exceeding 11 mBq/mL.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Recovery of Radioactivity in Urine, Feces and Both Routes Combined, as Percentage of Orally Administered Radioactive Dose of [14C]PF-07081532 | 360 hours | Urine and feces samples collected after a single oral dose of \[14C\]PF-07081532 30 mg (\ 250 nCi) in Period 1 were analyzed using Accelerator Mass Spectrometry (AMS). Blank pre-dose urine samples were collected within the 24 hours prior to dosing, blank fecal samples were collected from at least 1 bowel movement within the 48 hours prior to dosing. Following oral dosing, each urine void was collected across intervals of 0-12 hours, 12-24 hours, and each subsequent 24 hour interval up to 360 hours post dose, and all feces excreted were collected across each 24 hour interval up to 360 hours post dose. Recovery of radioactivity in urine, feces, and both routes combined, determined as percentage of the orally administered radioactive dose, are reported. |
| Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1 | Pre-dose (0 hours [hrs]) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, and 72 hrs post Period 1 Day 1 dosing | Plasma samples collected after a single oral dose of \[14C\]PF-07081532 30 mg (\ 250 nCi) were analyzed using Ultra Performance Liquid Chromatography coupled to High Resolution Mass Spectrometry (UPLC-HRMS). Relative abundance = (sum of radioactive content of fractions contributing to a particular peak/total circulating drug-related material \[total \[14C\] radioactivity in plasma\]) x 100%. Metabolites that were detected and identifiable (including coeluting metabolites reported together) are reported in this outcome measure (OM). |
| Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | 96 hours for urine samples and 144 hours for feces samples | Urine and feces samples collected after a single oral dose of \[14C\]PF-07081532 30 mg (\ 250 nCi) were analyzed using UPLC-HRMS. Blank pre-dose urine samples were collected within the 24 hours prior to dosing, blank fecal samples were collected from at least 1 bowel movement within the 48 hours prior to dosing. To obtain samples for evaluation of relative abundance in urine and feces, following oral dosing, each urine void was collected across intervals of 0-12 hours, 12-24 hours, and each subsequent 24 hour interval up to 96 hours post dose, and all feces excreted were collected across each 24 hour interval up to 144 hours post dose. Relative abundance was determined as sum of radioactive content of fractions contributing to a particular peak divided by total radioactive dose excreted in urine/feces respectively. Metabolites that were detected and identifiable (including coeluting metabolites reported together) are reported in this OM. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Cmax of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing | Maximum plasma concentration of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. |
| Plasma Time to Reach Cmax (Tmax) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing | Time to reach maximum plasma concentration of total \[14C\] and PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. |
| Area Under the Plasma Concentration-Time Curve to Infinity (AUCinf) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing | Area under the plasma concentration versus time curve from time zero to infinity of total \[14C\] after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. |
| AUCinf of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing | Area under the plasma concentration versus time curve from time zero to infinity of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. |
| Plasma Elimination Half Life (t1/2) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing | Plasma elimination half-life of total \[14C\] and PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. |
| Apparent Clearance of Drug From Plasma (CL/F) of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing | Apparent clearance of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F was calculated as dose/AUCinf, where AUCinf was area under the plasma concentration versus time curve from time zero to infinity. |
| Plasma Apparent Volume of Distribution (Vz/F) of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing | Apparent volume of distribution of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve, AUCinf is area under the plasma concentration versus time curve from time zero extrapolated to infinite time. |
| Plasma AUClast of [14C]PF-07081532 Following Intravenous (IV) Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of \[14C\]PF-07081532 after the participant received an oral (PO) dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). |
| Dose-Normalized Plasma AUClast (AUClast(dn) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Dose-normalized plasma AUClast of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (equivalent to 0.1 mg; approximately 1 hour after the oral dose). AUClast(dn) = AUClast/Dose, where AUClast = area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration, dose = IV dose of \[14C\]PF-07081532 (expressed in mg). |
| Plasma Cmax of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Maximum plasma concentration of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). |
| Dose-Normalized Plasma Cmax (Cmax (dn)) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Dose-normalized plasma Cmax of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (equivalent to 0.1 mg; approximately 1 hour after the oral dose). Cmax(dn) = Cmax/Dose, where Cmax = maximum concentration, dose = IV dose of \[14C\]PF-07081532 (expressed in mg). |
| Plasma Tmax of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Time to reach maximum plasma concentration of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). |
| Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing | Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of total \[14C\] after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. AUC for total \[14C\] is presented as nanogram equivalent \* hour/milliliter (ngEq\*hr/mL). |
| Dose-Normalized Plasma AUCinf (AUCinf(dn)) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Dose-normalized plasma AUCinf of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (equivalent to 0.1 mg; approximately 1 hour after the oral dose). AUCinf(dn) = AUCinf/Dose, where AUCinf = area under the plasma concentration versus time curve from time zero to infinity, dose = IV dose of \[14C\]PF-07081532 (expressed in mg). |
| Plasma t1/2 of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Plasma terminal half life of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). |
| Plasma Clearance (CL) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Plasma clearance of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL was calculated as (IV dose of \[14C\]PF-07081532) divided by (AUCinf of \[14C\]PF-07081532), where AUCinf = Area under the plasma concentration versus time curve from time zero to infinity. |
| Plasma Steady-State Volume of Distribution (Vss) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Plasma steady-state volume of distribution of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). Vss was calculated as CL \* MRT, where CL was the plasma clearance of \[14C\]PF-07081532, and MRT was the Mean Residence Time of \[14C\]PF-07081532. MRT = AUMCinf/AUCinf - (Infusion time/2), where AUMCinf was the area under the first moment curve from time zero to infinity, AUCinf = area under the plasma concentration versus time curve from time zero to infinity. |
| Plasma Mean Residence Time (MRT) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Plasma mean residence time of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). MRT = AUMCinf/AUCinf - (Infusion time/2), where AUMCinf was the area under the first moment curve from time zero to infinity, AUCinf = area under the plasma concentration versus time curve from time zero to infinity. |
| Absolute Oral Bioavailability (F) of PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hrs post oral dosing of unlabeled PF-07081532 on Period 2 Day 1 | F is a measure of the rate and extent of a drug reaching the systemic circulation in its unchanged form. F was estimated as the ratio of adjusted geometric means of dose-normalized plasma AUCinf following oral unlabeled PF-07081532 and IV \[14C\]PF-07081532 in Period 2, which is equivalent to the following equation: F = (AUCpo/\[14C\]\_AUCiv)\*(\[14C\]\_Doseiv/Dosepo). AUCpo and \[14C\]\_AUCiv were the AUCinf values of unlabeled PF-07081532 and \[14C\]PF-07081532, respectively in Period 2; Dosepo and \[14C\]\_Doseiv were the 30 mg oral dose of unlabeled PF-07081532 and each participant's individual IV dose of \[14C\]PF-07081532, respectively. |
| Fraction Absorbed (Fa) of PF-07081532 | Day 1 to Day 7 for both Period 1 and Period 2 | Fa was estimated as the ratio of adjusted geometric means of the % of administered radioactive dose excreted into urine following oral (Period 1) and IV (Period 2) dosing of \[14C\]PF-07081532. Urine radioactivity up to Day 7 in Period 1 was used to match the duration of Period 2 urine collection. Fa = (Total \[14C\]\_Urine\_PO\_Trunc/Total \[14C\]\_Urine\_IV) × (\[14C\] Doseiv/\[14C\] Dosepo). Total \[14C\]\_Urine\_PO\_Trunc = Total cumulative radioactivity excreted into urine from time zero up to Day 7 following Period 1 oral dosing, calculated as sum of (\[14C\] urine concentration × sample volume) for each collection interval. Total \[14C\]\_Urine\_IV = Total cumulative radioactivity excreted into urine from time zero to the time of last measurable concentration following Period 2 IV dosing, calculated as sum of (\[14C\] concentration × urine collection volume) for each collection interval (= sum of collection intervals). \[14C\] Dose = radioactivity dose (PO in Period 1, IV in Period 2) for each participant. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Maximum of 11 weeks | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. |
| Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | Maximum of 11 weeks | Laboratory tests included hematology, clinical chemistry and urinalysis. Laboratory abnormalities reported in at least 1 participant are reported in this OM. |
| Number of Participants With Post-Baseline Vital Signs Data Meeting Pre-Defined Criteria | Maximum of 11 weeks | Vital signs data included supine systolic and diastolic blood pressure (BP) and pulse rate. Potentially clinically significant vital signs abnormalities are defined as: systolic BP - minimum (min) absolute result \<90 mmHg, maximum (max) increase or decrease from baseline ≥30 mmHg; diastolic BP - min absolute result \<50 mmHg, max increase or decrease from baseline ≥20 mmHg; supine pulse rate - min absolute result \<40 beat per minute (bpm), max absolute result \>120 bpm. Participants with vital signs data meeting any criteria above are reported in this OM. |
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Criteria | Maximum of 11 weeks | ECG data included heart rate, PR interval, QT interval, QT Interval (Fridericia's Correction) (QTcF) and QRS complex. Potentially clinically significant ECG abnormalities are categorized as follows: Uncorrected QT value \>500 millisecond (msec). QTcF - absolute value \>450 and ≤480 msec; absolute value \>480 and ≤500 msec; absolute value \>500 msec; increase from baseline \>30 and ≤60 msec; increase from baseline \>60 msec. PR interval - max absolute value ≥300 msec; baseline value \>200 msec and ≥25% increase from baseline; baseline value ≤200 msec and ≥50% increase from baseline. QRS complex - max absolute value ≥140 msec; ≥50% increase from baseline. Participants with ECG data meeting any criteria above are reported in this OM, if any. |
| Plasma AUCinf of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1 | Area under the plasma concentration versus time curve from time zero to infinity of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). |
| AUClast of PF-07081532 After A Single Oral Dose of [14]PF-07081532 in Period 1 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing | Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. |
| Plasma Maximum Observed Concentration (Cmax) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing | Maximum plasma concentration of total \[14C\] after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. |
Countries
Netherlands
Participant flow
Pre-assignment details
A total of 6 participants were enrolled and treated in both Period 1 and Period 2 of the study.
Participants by arm
| Arm | Count |
|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral; Period 2: PF-07081532 30 mg Oral + [14C]PF-07081532 100 µg IV In Period 1, participants received a single oral dose of \[14C\]PF-07081532 30 mg; in Period 2, participants received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Period 1: [14C]PF-07081532 30 mg Oral; Period 2: PF-07081532 30 mg Oral + [14C]PF-07081532 100 µg IV |
|---|---|
| Age, Customized 18-25 years | 0 Participants |
| Age, Customized <18 years | 0 Participants |
| Age, Customized 26-35 years | 5 Participants |
| Age, Customized 36-45 years | 0 Participants |
| Age, Customized >45 years | 1 Participants |
| Age, Customized | 32 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized White | 5 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 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1
Plasma samples collected after a single oral dose of \[14C\]PF-07081532 30 mg (\ 250 nCi) were analyzed using Ultra Performance Liquid Chromatography coupled to High Resolution Mass Spectrometry (UPLC-HRMS). Relative abundance = (sum of radioactive content of fractions contributing to a particular peak/total circulating drug-related material \[total \[14C\] radioactivity in plasma\]) x 100%. Metabolites that were detected and identifiable (including coeluting metabolites reported together) are reported in this outcome measure (OM).
Time frame: Pre-dose (0 hours [hrs]) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, and 72 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants who received study intervention of \[14C\]PF-07081532 in Period 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1 | 767a (hydroxy glucuronide) | 1.2 Percentage of circulating radioactivity |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1 | PF-07943285 (hydroxy glucuronide) | 8.8 Percentage of circulating radioactivity |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1 | 767c (hydroxy glucuronide) | 0.4 Percentage of circulating radioactivity |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1 | 671 (hydroxy sulfate) | 0.6 Percentage of circulating radioactivity |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1 | Coeluting components: PF-07214855, PF-07260051, PF-07943284 | 9.1 Percentage of circulating radioactivity |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1 | PF-07081532 | 79.3 Percentage of circulating radioactivity |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1 | Unassigned [14C] | 0.6 Percentage of circulating radioactivity |
Primary
Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1
Urine and feces samples collected after a single oral dose of \[14C\]PF-07081532 30 mg (\ 250 nCi) were analyzed using UPLC-HRMS. Blank pre-dose urine samples were collected within the 24 hours prior to dosing, blank fecal samples were collected from at least 1 bowel movement within the 48 hours prior to dosing. To obtain samples for evaluation of relative abundance in urine and feces, following oral dosing, each urine void was collected across intervals of 0-12 hours, 12-24 hours, and each subsequent 24 hour interval up to 96 hours post dose, and all feces excreted were collected across each 24 hour interval up to 144 hours post dose. Relative abundance was determined as sum of radioactive content of fractions contributing to a particular peak divided by total radioactive dose excreted in urine/feces respectively. Metabolites that were detected and identifiable (including coeluting metabolites reported together) are reported in this OM.
Time frame: 96 hours for urine samples and 144 hours for feces samples
Population: The analysis population included all participants who received study intervention of \[14C\]PF-07081532 in Period 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | Urine: PF-07943285 (hydroxy glucuronide) | 0.1 Percentage of radioactive dose |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | Urine: 767c (hydroxy glucuronide) | 0.03 Percentage of radioactive dose |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | Urine: coeluting components PF-07214855 , PF-07260051 and PF-07943284 | 0.2 Percentage of radioactive dose |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | Urine: PF-07081532 | 0.04 Percentage of radioactive dose |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | Urine: Unassigned [14C] | 4.33 Percentage of radioactive dose |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | Feces: PF-07240437 (catechol) | 3.89 Percentage of radioactive dose |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | Feces: PF-07943283 (hydroxy) | 13.6 Percentage of radioactive dose |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | Feces: coeluting components PF-07260051 and PF-07943284 | 24.7 Percentage of radioactive dose |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | Feces: PF-07081532 | 13.2 Percentage of radioactive dose |
| Period 1: [14C]PF-07081532 30 mg Oral | Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1 | Feces: Unassigned [14C] | 23.2 Percentage of radioactive dose |
Primary
Total Recovery of Radioactivity in Urine, Feces and Both Routes Combined, as Percentage of Orally Administered Radioactive Dose of [14C]PF-07081532
Urine and feces samples collected after a single oral dose of \[14C\]PF-07081532 30 mg (\ 250 nCi) in Period 1 were analyzed using Accelerator Mass Spectrometry (AMS). Blank pre-dose urine samples were collected within the 24 hours prior to dosing, blank fecal samples were collected from at least 1 bowel movement within the 48 hours prior to dosing. Following oral dosing, each urine void was collected across intervals of 0-12 hours, 12-24 hours, and each subsequent 24 hour interval up to 360 hours post dose, and all feces excreted were collected across each 24 hour interval up to 360 hours post dose. Recovery of radioactivity in urine, feces, and both routes combined, determined as percentage of the orally administered radioactive dose, are reported.
Time frame: 360 hours
Population: The analysis population included all evaluable participants who had received 1 dose of \[14C\]PF-07081532 in Period 1 with complete total radioactivity concentration (urinary and fecal) data and who had no protocol deviations that might have affected the extent of excretion analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Total Recovery of Radioactivity in Urine, Feces and Both Routes Combined, as Percentage of Orally Administered Radioactive Dose of [14C]PF-07081532 | Urine | 4.7 Percentage of radioactive dose | Standard Deviation 0.6 |
| Period 1: [14C]PF-07081532 30 mg Oral | Total Recovery of Radioactivity in Urine, Feces and Both Routes Combined, as Percentage of Orally Administered Radioactive Dose of [14C]PF-07081532 | Feces | 78.6 Percentage of radioactive dose | Standard Deviation 6.7 |
| Period 1: [14C]PF-07081532 30 mg Oral | Total Recovery of Radioactivity in Urine, Feces and Both Routes Combined, as Percentage of Orally Administered Radioactive Dose of [14C]PF-07081532 | Urine + Feces | 83.4 Percentage of radioactive dose | Standard Deviation 6.9 |
Secondary
Absolute Oral Bioavailability (F) of PF-07081532 in Period 2
F is a measure of the rate and extent of a drug reaching the systemic circulation in its unchanged form. F was estimated as the ratio of adjusted geometric means of dose-normalized plasma AUCinf following oral unlabeled PF-07081532 and IV \[14C\]PF-07081532 in Period 2, which is equivalent to the following equation: F = (AUCpo/\[14C\]\_AUCiv)\*(\[14C\]\_Doseiv/Dosepo). AUCpo and \[14C\]\_AUCiv were the AUCinf values of unlabeled PF-07081532 and \[14C\]PF-07081532, respectively in Period 2; Dosepo and \[14C\]\_Doseiv were the 30 mg oral dose of unlabeled PF-07081532 and each participant's individual IV dose of \[14C\]PF-07081532, respectively.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hrs post oral dosing of unlabeled PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with PF-07081532 and \[14C\]PF-07081532 in Period 2 who had at least one of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Absolute Oral Bioavailability (F) of PF-07081532 in Period 2 | 90.79 Percent |
Secondary
Apparent Clearance of Drug From Plasma (CL/F) of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Apparent clearance of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F was calculated as dose/AUCinf, where AUCinf was area under the plasma concentration versus time curve from time zero to infinity.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 1 who had at least one of the PF-07081532 or total \[14C\] PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Apparent Clearance of Drug From Plasma (CL/F) of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | 0.5851 Liter/hour (L/hr) | Geometric Coefficient of Variation 22 |
Secondary
Area Under the Plasma Concentration-Time Curve to Infinity (AUCinf) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1
Area under the plasma concentration versus time curve from time zero to infinity of total \[14C\] after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 1 who had at least one of the PF-07081532 or total \[14C\] PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Area Under the Plasma Concentration-Time Curve to Infinity (AUCinf) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1 | 76050 ngEq*hr/mL | Geometric Coefficient of Variation 17 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1
Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of total \[14C\] after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. AUC for total \[14C\] is presented as nanogram equivalent \* hour/milliliter (ngEq\*hr/mL).
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 1 who had at least one of the PF-07081532 or total \[14C\] PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1 | 74360 ngEq*hr/mL | Geometric Coefficient of Variation 17 |
Secondary
AUCinf of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Area under the plasma concentration versus time curve from time zero to infinity of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 1 who had at least one of the PF-07081532 or total \[14C\] PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | AUCinf of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | 51370 ng*hr/mL | Geometric Coefficient of Variation 21 |
Secondary
AUClast of PF-07081532 After A Single Oral Dose of [14]PF-07081532 in Period 1
Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 1 who had at least one of the PF-07081532 or total \[14C\] PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | AUClast of PF-07081532 After A Single Oral Dose of [14]PF-07081532 in Period 1 | 49380 nanogram*hr/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 21 |
Secondary
Dose-Normalized Plasma AUCinf (AUCinf(dn)) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Dose-normalized plasma AUCinf of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (equivalent to 0.1 mg; approximately 1 hour after the oral dose). AUCinf(dn) = AUCinf/Dose, where AUCinf = area under the plasma concentration versus time curve from time zero to infinity, dose = IV dose of \[14C\]PF-07081532 (expressed in mg).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Dose-Normalized Plasma AUCinf (AUCinf(dn)) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | 1844 ng*hr/mL/mg | Geometric Coefficient of Variation 29 |
Secondary
Dose-Normalized Plasma AUClast (AUClast(dn) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Dose-normalized plasma AUClast of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (equivalent to 0.1 mg; approximately 1 hour after the oral dose). AUClast(dn) = AUClast/Dose, where AUClast = area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration, dose = IV dose of \[14C\]PF-07081532 (expressed in mg).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Dose-Normalized Plasma AUClast (AUClast(dn) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | 1831 ng*hr/mL/mg | Geometric Coefficient of Variation 28 |
Secondary
Dose-Normalized Plasma Cmax (Cmax (dn)) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Dose-normalized plasma Cmax of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (equivalent to 0.1 mg; approximately 1 hour after the oral dose). Cmax(dn) = Cmax/Dose, where Cmax = maximum concentration, dose = IV dose of \[14C\]PF-07081532 (expressed in mg).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Dose-Normalized Plasma Cmax (Cmax (dn)) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | 228.5 ng/mL/mg | Geometric Coefficient of Variation 13 |
Secondary
Fraction Absorbed (Fa) of PF-07081532
Fa was estimated as the ratio of adjusted geometric means of the % of administered radioactive dose excreted into urine following oral (Period 1) and IV (Period 2) dosing of \[14C\]PF-07081532. Urine radioactivity up to Day 7 in Period 1 was used to match the duration of Period 2 urine collection. Fa = (Total \[14C\]\_Urine\_PO\_Trunc/Total \[14C\]\_Urine\_IV) × (\[14C\] Doseiv/\[14C\] Dosepo). Total \[14C\]\_Urine\_PO\_Trunc = Total cumulative radioactivity excreted into urine from time zero up to Day 7 following Period 1 oral dosing, calculated as sum of (\[14C\] urine concentration × sample volume) for each collection interval. Total \[14C\]\_Urine\_IV = Total cumulative radioactivity excreted into urine from time zero to the time of last measurable concentration following Period 2 IV dosing, calculated as sum of (\[14C\] concentration × urine collection volume) for each collection interval (= sum of collection intervals). \[14C\] Dose = radioactivity dose (PO in Period 1, IV in Period 2) for each participant.
Time frame: Day 1 to Day 7 for both Period 1 and Period 2
Population: The analysis population included all participants who received at least 1 dose of study intervention and had at least 1 of the PF-07081532 or \[14C\]PF-07081532 parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Fraction Absorbed (Fa) of PF-07081532 | 79.91 Percent |
Secondary
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Criteria
ECG data included heart rate, PR interval, QT interval, QT Interval (Fridericia's Correction) (QTcF) and QRS complex. Potentially clinically significant ECG abnormalities are categorized as follows: Uncorrected QT value \>500 millisecond (msec). QTcF - absolute value \>450 and ≤480 msec; absolute value \>480 and ≤500 msec; absolute value \>500 msec; increase from baseline \>30 and ≤60 msec; increase from baseline \>60 msec. PR interval - max absolute value ≥300 msec; baseline value \>200 msec and ≥25% increase from baseline; baseline value ≤200 msec and ≥50% increase from baseline. QRS complex - max absolute value ≥140 msec; ≥50% increase from baseline. Participants with ECG data meeting any criteria above are reported in this OM, if any.
Time frame: Maximum of 11 weeks
Population: The safety analysis population included all participants who received at least 1 dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Criteria | 0 Participants |
| Period 2: PF-07081532 30 mg Oral + [14C]PF-07081532 100 µg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Criteria | 0 Participants |
Secondary
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
Laboratory tests included hematology, clinical chemistry and urinalysis. Laboratory abnormalities reported in at least 1 participant are reported in this OM.
Time frame: Maximum of 11 weeks
Population: The safety analysis population included all participants who received at least 1 dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | 1 Participants |
| Period 2: PF-07081532 30 mg Oral + [14C]PF-07081532 100 µg IV | Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality) | 0 Participants |
Secondary
Number of Participants With Post-Baseline Vital Signs Data Meeting Pre-Defined Criteria
Vital signs data included supine systolic and diastolic blood pressure (BP) and pulse rate. Potentially clinically significant vital signs abnormalities are defined as: systolic BP - minimum (min) absolute result \<90 mmHg, maximum (max) increase or decrease from baseline ≥30 mmHg; diastolic BP - min absolute result \<50 mmHg, max increase or decrease from baseline ≥20 mmHg; supine pulse rate - min absolute result \<40 beat per minute (bpm), max absolute result \>120 bpm. Participants with vital signs data meeting any criteria above are reported in this OM.
Time frame: Maximum of 11 weeks
Population: The safety analysis population included all participants who received at least 1 dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Number of Participants With Post-Baseline Vital Signs Data Meeting Pre-Defined Criteria | 0 Participants |
| Period 2: PF-07081532 30 mg Oral + [14C]PF-07081532 100 µg IV | Number of Participants With Post-Baseline Vital Signs Data Meeting Pre-Defined Criteria | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect.
Time frame: Maximum of 11 weeks
Population: The safety analysis population included all participants who received at least 1 dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-causality TEAE | 4 Participants |
| Period 1: [14C]PF-07081532 30 mg Oral | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAE | 2 Participants |
| Period 1: [14C]PF-07081532 30 mg Oral | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-causality SAE | 0 Participants |
| Period 2: PF-07081532 30 mg Oral + [14C]PF-07081532 100 µg IV | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-causality TEAE | 2 Participants |
| Period 2: PF-07081532 30 mg Oral + [14C]PF-07081532 100 µg IV | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAE | 1 Participants |
| Period 2: PF-07081532 30 mg Oral + [14C]PF-07081532 100 µg IV | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-causality SAE | 0 Participants |
Secondary
Plasma Apparent Volume of Distribution (Vz/F) of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Apparent volume of distribution of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve, AUCinf is area under the plasma concentration versus time curve from time zero extrapolated to infinite time.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 1 who had at least one of the PF-07081532 or total \[14C\] PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Apparent Volume of Distribution (Vz/F) of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | 16.13 L | Geometric Coefficient of Variation 21 |
Secondary
Plasma AUCinf of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Area under the plasma concentration versus time curve from time zero to infinity of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma AUCinf of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | 186.9 ng*hr/mL | Geometric Coefficient of Variation 32 |
Secondary
Plasma AUClast of [14C]PF-07081532 Following Intravenous (IV) Administration of [14C]PF-07081532 in Period 2
Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of \[14C\]PF-07081532 after the participant received an oral (PO) dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma AUClast of [14C]PF-07081532 Following Intravenous (IV) Administration of [14C]PF-07081532 in Period 2 | 185.9 ng*hr/mL | Geometric Coefficient of Variation 32 |
Secondary
Plasma Clearance (CL) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Plasma clearance of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL was calculated as (IV dose of \[14C\]PF-07081532) divided by (AUCinf of \[14C\]PF-07081532), where AUCinf = Area under the plasma concentration versus time curve from time zero to infinity.
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Clearance (CL) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | 0.5420 L/hr | Geometric Coefficient of Variation 29 |
Secondary
Plasma Cmax of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Maximum plasma concentration of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Cmax of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | 23.20 ng/mL | Geometric Coefficient of Variation 16 |
Secondary
Plasma Cmax of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Maximum plasma concentration of PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 1 who had at least one of the PF-07081532 or total \[14C\] PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Cmax of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | 2874 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 10 |
Secondary
Plasma Elimination Half Life (t1/2) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Plasma elimination half-life of total \[14C\] and PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 1 who had at least one of the PF-07081532 or total \[14C\] PK parameters of interest.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Elimination Half Life (t1/2) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Total [14C] | 65.20 hour | Standard Deviation 6.7308 |
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Elimination Half Life (t1/2) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | PF-07081532 | 19.42 hour | Standard Deviation 3.5583 |
Secondary
Plasma Maximum Observed Concentration (Cmax) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1
Maximum plasma concentration of total \[14C\] after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 1 who had at least one of the PF-07081532 or total \[14C\] PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Maximum Observed Concentration (Cmax) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1 | 2934 nanogram equivalent/milliliter (ngEq/mL) | Geometric Coefficient of Variation 10 |
Secondary
Plasma Mean Residence Time (MRT) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Plasma mean residence time of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). MRT = AUMCinf/AUCinf - (Infusion time/2), where AUMCinf was the area under the first moment curve from time zero to infinity, AUCinf = area under the plasma concentration versus time curve from time zero to infinity.
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Mean Residence Time (MRT) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | 19.77 hour | Geometric Coefficient of Variation 21 |
Secondary
Plasma Steady-State Volume of Distribution (Vss) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Plasma steady-state volume of distribution of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose). Vss was calculated as CL \* MRT, where CL was the plasma clearance of \[14C\]PF-07081532, and MRT was the Mean Residence Time of \[14C\]PF-07081532. MRT = AUMCinf/AUCinf - (Infusion time/2), where AUMCinf was the area under the first moment curve from time zero to infinity, AUCinf = area under the plasma concentration versus time curve from time zero to infinity.
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Steady-State Volume of Distribution (Vss) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | 10.70 L | Geometric Coefficient of Variation 15 |
Secondary
Plasma t1/2 of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Plasma terminal half life of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma t1/2 of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | 21.02 hour | Standard Deviation 2.9027 |
Secondary
Plasma Time to Reach Cmax (Tmax) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
Time to reach maximum plasma concentration of total \[14C\] and PF-07081532 after the participant received a single oral dose of \[14C\]PF-07081532 30 mg (approximately 250 nCi \[14C\]) in Period 1.
Time frame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 1 who had at least one of the PF-07081532 or total \[14C\] PK parameters of interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Time to Reach Cmax (Tmax) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | Total [14C] | 4.93 hour |
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Time to Reach Cmax (Tmax) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1 | PF-07081532 | 3.93 hour |
Secondary
Plasma Tmax of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
Time to reach maximum plasma concentration of \[14C\]PF-07081532 after the participant received an oral dose of unlabeled PF-07081532 30 mg, followed by IV infusion of \[14C\]PF-07081532 100 µg (approximately 1 hour after the oral dose).
Time frame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
Population: The analysis population included all participants dosed with \[14C\]PF-07081532 in Period 2 who had at least one of the \[14C\]PF-07081532 PK parameters of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period 1: [14C]PF-07081532 30 mg Oral | Plasma Tmax of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2 | 0.250 hour |