Healthy Volunteer
Conditions
Keywords
radiolabeled, healthy volunteers
Brief summary
The rationale for this study is to investigate the absorption, metabolism and excretion of \[14C\]PF 02341066 and characterize plasma, fecal and urinary radioactivity, and identify any metabolites, if possible, of \[14C\]PF 02341066 in humans.
Interventions
DRUGPF-02341066
oral suspension, single 250 mg dose of PF 02341066 containing approximately 100 µCi of \[14C\]PF 02341066
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests). * Body Mass Index (BMI) of 17.5 to 30.5 kg/m\^2; and a total body weight \>50 kg (110 lbs).
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). * Any condition possibly affecting drug absorption (eg, gastrectomy). * A positive urine drug screen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours (hrs), 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | — |
| Area Under the Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Area under the concentration time-curve from zero to the last measured plasma concentration (AUClast). |
| Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Plasma Decay Half Life (t1/2) | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Plasma Decay half-life is the time measured for the concentration to decrease by one half. |
| Apparent Oral Clearance (CL/F) of Plasma PF-02341066 | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. |
| Apparent Volume of Distribution (V/F) in Plasma | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. |
| Renal Clearance (CLr) of PF-02341066 | Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose | CLr is the volume of plasma from which a substance is completely removed by the kidney in a given amount of time. |
| Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to Infinite Time (Ae) | Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose | Ae = concentration of unchanged drug excreted in the urine multiplied by volume of unchanged drug excreted in urine. |
| Total Amount of Unchanged Drug Excreted in the Urine Expressed as Percent of Dose From Time Zero to Infinite Time [Ae(%)] | Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose | — |
| Maximum Observed Concentration in Plasma Radioactivity (Cmax) | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Time to Reach Maximum Observed Plasma Radioactivity Concentration (Tmax) | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Area Under the Curve From Time Zero to Last Quantifiable Plasma Radioactivity Concentration (AUClast) | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Area under the concentration time-curve from zero to the last measured plasma concentration. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Area Under the Plasma Radioactivity Concentration Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Area under the concentration curve from time zero to extrapolated infinite time \[AUC (0 - ∞)\] in plasma. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Decay Half Life (t1/2) of Radioactivity in Plasma | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Plasma decay half-life is the time measured for the plasma radioactivity concentration to decrease by one half. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Apparent Oral Clearance (CL/F) of Plasma Radioactivity | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Apparent Volume of Distribution (V/F) in Plasma Radioactivity | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Maximum Observed Concentration of Radioactivity in Whole Blood (Cmax) | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Time to Reach Maximum Observed Concentration (Tmax) of Radioactivity in Whole Blood | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Time to Reach Maximum Observed Concentration (Tmax) of Radioactivity in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Radioactivity in Whole Blood | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Area under the concentration time-curve from zero to the last measured concentration (AUClast) in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Radioactivity in Whole Blood | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Area under the concentration curve from time zero to extrapolated infinite time \[AUC (0 - ∞)\] in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Decay Half-life (t1/2) of Radioactivity in Whole Blood | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Decay half life (t1/2) is the time measured for the concentration to decrease by one half in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Apparent Oral Clearance of Radioactivity From Whole Blood (CL/F) | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Apparent Volume of Distribution of Radioactivity in Whole Blood (V/F) | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066. |
| Total [14C] Data in Urine | Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose | Cumulative amount excreted in urine at specified intervals after administration of a single 250-mg (100 μCi) oral dose of \[14C\]PF-02341066. |
| Total [14C] Data in Feces | From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose | Cumulative amount excreted in feces at specified intervals after administration of a single 250-mg (100 μCi) oral dose of \[14C\]PF-02341066. |
| Overall Cumulative Percent Recovery of Radioactivity | Pre-dose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose for urine and Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose for feces | Overall cumulative percent of radioactive dose recovered in urine, feces and toilet tissue at specified intervals after administration of a single 250-mg (100 μCi) oral dose of \[14C\]PF-02341066. |
| Identification and Profiling of Metabolites of [14C]PF-02341066 in Plasma | Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose | Identification was done by Radio-High Performance liquid chromatography (HPLC) chromatogram. Relative abundance (profiling) of metabolites in chromatogram were determined by dividing sum of radioactive content of fractions contributing to particular peak by sum of radioactive content of all fractions constructing the radio chromatogram. Metabolites accounting for an average of greater than or equal to (\>=) 10% of total recoverable radioactivity in plasma were summarized. Radioactivity corresponds to 100 μCi \[14C\] PF-02341066. |
| Identification and Profiling of Metabolites of [14C]PF-02341066 in Feces | From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose | In feces, metabolite abundance (profiling) was calculated by multiplying the fractional contribution of radioactive response for the peak in the Radio-HPLC chromatogram to the total radioactivity detected by the percent of administered dose recovered in the matrix. Only those metabolites that were a component of a chromatographic peak that accounted for an average of \>=1% of the administered dose, were summarized. Radioactivity corresponds to 100 μCi \[14C\] PF-02341066. |
| Identification and Profiling of Metabolites of [14C]PF-02341066 in Urine | Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose | In urine, metabolite abundance (profiling) was calculated by multiplying the fractional contribution of radioactive response for the peak in the Radio-HPLC chromatogram to the total radioactivity detected by the percent of administered dose recovered in the matrix. Only those metabolites that were a component of a chromatographic peak that accounted for an average of \>=1% of the administered dose, were summarized. Radioactivity corresponds to 100 μCi \[14C\] PF-02341066. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-02341066 250 mg Single oral dose of PF-02341066 250 mg containing 100 μCi \[14C\]. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | PF-02341066 250 mg |
|---|---|
| Age Continuous | 43.2 years STANDARD_DEVIATION 1.8 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Apparent Oral Clearance (CL/F) of Plasma PF-02341066
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Apparent Oral Clearance (CL/F) of Plasma PF-02341066 | 90.140 L/hr | Standard Deviation 23.984 |
Primary
Apparent Oral Clearance (CL/F) of Plasma Radioactivity
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: Data was insufficient to analyze as only 2 participants were evaluable for the parameter.
Primary
Apparent Oral Clearance of Radioactivity From Whole Blood (CL/F)
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: Data was insufficient to analyze as only 2 participants were evaluable for the parameter.
Primary
Apparent Volume of Distribution of Radioactivity in Whole Blood (V/F)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: Data was insufficient to analyze as only 2 participants were evaluable for the parameter.
Primary
Apparent Volume of Distribution (V/F) in Plasma
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Apparent Volume of Distribution (V/F) in Plasma | 12110.0 L | Standard Deviation 4544.5 |
Primary
Apparent Volume of Distribution (V/F) in Plasma Radioactivity
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (V/F) is influenced by the fraction absorbed. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: Data was insufficient to analyze as only 2 participants were evaluable for the parameter.
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Radioactivity in Whole Blood
Area under the concentration curve from time zero to extrapolated infinite time \[AUC (0 - ∞)\] in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: Data was insufficient to analyze as only 2 participants were evaluable for the parameter.
Primary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Radioactivity in Whole Blood
Area under the concentration time-curve from zero to the last measured concentration (AUClast) in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Radioactivity in Whole Blood | 7032.0 ng-eq*hr/mL | Standard Deviation 1284.2 |
Primary
Area Under the Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast)
Area under the concentration time-curve from zero to the last measured plasma concentration (AUClast).
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Area Under the Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) | 2686.0 ng*hr/mL | Standard Deviation 1119.6 |
Primary
Area Under the Curve From Time Zero to Last Quantifiable Plasma Radioactivity Concentration (AUClast)
Area under the concentration time-curve from zero to the last measured plasma concentration. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Area Under the Curve From Time Zero to Last Quantifiable Plasma Radioactivity Concentration (AUClast) | 22830.0 ng-eq*hr/mL | Standard Deviation 2636.4 |
Primary
Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 2777.0 ng*hr/mL | Standard Deviation 1114.9 |
Primary
Area Under the Plasma Radioactivity Concentration Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
Area under the concentration curve from time zero to extrapolated infinite time \[AUC (0 - ∞)\] in plasma. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: Data was insufficient to analyze as only 2 participants were evaluable for the parameter.
Primary
Decay Half Life (t1/2) of Radioactivity in Plasma
Plasma decay half-life is the time measured for the plasma radioactivity concentration to decrease by one half. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: Data was insufficient to analyze as only 2 participants were evaluable for the parameter.
Primary
Decay Half-life (t1/2) of Radioactivity in Whole Blood
Decay half life (t1/2) is the time measured for the concentration to decrease by one half in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: Data was insufficient to analyze as only 2 participants were evaluable for the parameter.
Primary
Identification and Profiling of Metabolites of [14C]PF-02341066 in Feces
In feces, metabolite abundance (profiling) was calculated by multiplying the fractional contribution of radioactive response for the peak in the Radio-HPLC chromatogram to the total radioactivity detected by the percent of administered dose recovered in the matrix. Only those metabolites that were a component of a chromatographic peak that accounted for an average of \>=1% of the administered dose, were summarized. Radioactivity corresponds to 100 μCi \[14C\] PF-02341066.
Time frame: From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02341066 250 mg | Identification and Profiling of Metabolites of [14C]PF-02341066 in Feces | PF-02341066 | 53.5 Percentage of radioactive dose |
| PF-02341066 250 mg | Identification and Profiling of Metabolites of [14C]PF-02341066 in Feces | M8 | NA Percentage of radioactive dose |
Primary
Identification and Profiling of Metabolites of [14C]PF-02341066 in Plasma
Identification was done by Radio-High Performance liquid chromatography (HPLC) chromatogram. Relative abundance (profiling) of metabolites in chromatogram were determined by dividing sum of radioactive content of fractions contributing to particular peak by sum of radioactive content of all fractions constructing the radio chromatogram. Metabolites accounting for an average of greater than or equal to (\>=) 10% of total recoverable radioactivity in plasma were summarized. Radioactivity corresponds to 100 μCi \[14C\] PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02341066 250 mg | Identification and Profiling of Metabolites of [14C]PF-02341066 in Plasma | PF-02341066 | 33.1 Percentage of recovered radioactivity |
| PF-02341066 250 mg | Identification and Profiling of Metabolites of [14C]PF-02341066 in Plasma | M10, PF-06260182 | 10.2 Percentage of recovered radioactivity |
Primary
Identification and Profiling of Metabolites of [14C]PF-02341066 in Urine
In urine, metabolite abundance (profiling) was calculated by multiplying the fractional contribution of radioactive response for the peak in the Radio-HPLC chromatogram to the total radioactivity detected by the percent of administered dose recovered in the matrix. Only those metabolites that were a component of a chromatographic peak that accounted for an average of \>=1% of the administered dose, were summarized. Radioactivity corresponds to 100 μCi \[14C\] PF-02341066.
Time frame: Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-02341066 250 mg | Identification and Profiling of Metabolites of [14C]PF-02341066 in Urine | PF-02341066 | 2.4 Percentage of radioactive dose |
| PF-02341066 250 mg | Identification and Profiling of Metabolites of [14C]PF-02341066 in Urine | M8 | 4.5 Percentage of radioactive dose |
Primary
Maximum Observed Concentration in Plasma Radioactivity (Cmax)
Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Maximum Observed Concentration in Plasma Radioactivity (Cmax) | 435.600 nanogram-equivalent/milliliter(ng-eq/mL) | Standard Deviation 82.072 |
Primary
Maximum Observed Concentration of Radioactivity in Whole Blood (Cmax)
Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Maximum Observed Concentration of Radioactivity in Whole Blood (Cmax) | 312.300 ng-eq/mL | Standard Deviation 62.669 |
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours (hrs), 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The Pharmacokinetic (PK) parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Maximum Observed Plasma Concentration (Cmax) | 109.400 ng/mL | Standard Deviation 54.153 |
Primary
Overall Cumulative Percent Recovery of Radioactivity
Overall cumulative percent of radioactive dose recovered in urine, feces and toilet tissue at specified intervals after administration of a single 250-mg (100 μCi) oral dose of \[14C\]PF-02341066.
Time frame: Pre-dose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose for urine and Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose for feces
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-02341066 250 mg | Overall Cumulative Percent Recovery of Radioactivity | Urine | 22.20 Percent recovery of radioactivity | Standard Deviation 4.63 |
| PF-02341066 250 mg | Overall Cumulative Percent Recovery of Radioactivity | Feces | 63.10 Percent recovery of radioactivity | Standard Deviation 5.93 |
| PF-02341066 250 mg | Overall Cumulative Percent Recovery of Radioactivity | Overall | 85.20 Percent recovery of radioactivity | Standard Deviation 8.38 |
Primary
Plasma Decay Half Life (t1/2)
Plasma Decay half-life is the time measured for the concentration to decrease by one half.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Plasma Decay Half Life (t1/2) | 93.970 hr | Standard Deviation 13.797 |
Primary
Renal Clearance (CLr) of PF-02341066
CLr is the volume of plasma from which a substance is completely removed by the kidney in a given amount of time.
Time frame: Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose
Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Renal Clearance (CLr) of PF-02341066 | 2.11 L/hr | Standard Deviation 0.29 |
Primary
Time to Reach Maximum Observed Concentration (Tmax) of Radioactivity in Whole Blood
Time to Reach Maximum Observed Concentration (Tmax) of Radioactivity in whole blood. Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-02341066 250 mg | Time to Reach Maximum Observed Concentration (Tmax) of Radioactivity in Whole Blood | 4.00 hr |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-02341066 250 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 2.99 hr |
Primary
Time to Reach Maximum Observed Plasma Radioactivity Concentration (Tmax)
Radioactivity corresponds to 100 μCi \[14C\]PF-02341066.
Time frame: Pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hrs, 36 hrs, 48 hrs, then after every 24 hrs until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-02341066 250 mg | Time to Reach Maximum Observed Plasma Radioactivity Concentration (Tmax) | 5.00 hr |
Primary
Total [14C] Data in Feces
Cumulative amount excreted in feces at specified intervals after administration of a single 250-mg (100 μCi) oral dose of \[14C\]PF-02341066.
Time frame: From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Total [14C] Data in Feces | 160000000 ng-eq | Standard Deviation 15000000 |
Primary
Total [14C] Data in Urine
Cumulative amount excreted in urine at specified intervals after administration of a single 250-mg (100 μCi) oral dose of \[14C\]PF-02341066.
Time frame: Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose
Population: The radioactivity parameter analysis population included all treated participants who had at least 1 of the radioactivity parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Total [14C] Data in Urine | 56200000 ng-eq | Standard Deviation 11500000 |
Primary
Total Amount of Unchanged Drug Excreted in the Urine Expressed as Percent of Dose From Time Zero to Infinite Time [Ae(%)]
Time frame: Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose
Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Total Amount of Unchanged Drug Excreted in the Urine Expressed as Percent of Dose From Time Zero to Infinite Time [Ae(%)] | 2.339 Percent dose of unchanged drug | Standard Deviation 1.38 |
Primary
Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to Infinite Time (Ae)
Ae = concentration of unchanged drug excreted in the urine multiplied by volume of unchanged drug excreted in urine.
Time frame: Predose, 0 to 4, 4 to 8, 8 to 16, 16 to 24 to 36, 36 to 48 hrs and then after every 24 hrs until up to 480 hrs post-dose
Population: The PK parameter analysis population included all treated participants who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-02341066 250 mg | Total Amount of Unchanged Drug Excreted in the Urine From Time Zero to Infinite Time (Ae) | 5.847 mg | Standard Deviation 3.45 |