Radiolabeled [14C]PF-02341066 Study To Investigate The Absorption, Metabolism And Excretion In Healthy Male Volunteers
- Registration Number
- NCT01082380
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 6
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 PF-02341066 -
- Primary Outcome Measures
Name Time Method 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇺🇸New Haven, Connecticut, United States