Radiolabeled [14C]PF-02341066 Study To Investigate The Absorption, Metabolism And Excretion In Healthy Male Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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A Phase One Open-Label Single-Radiolabeled Dose Study To Investigate The Absorption, Metabolism And Excretion Of [14C]PF-02341066 In Healthy Male Volunteers

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: PF-02341066


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: PF-02341066<br>* oral suspension, single 250 mg dose of PF 02341066 containing approximately 100 µCi of [14C]PF 02341066<br>* Other names: crizotinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Area under the concentration time-curve from zero to the last measured 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 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 - ∞). | 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 (t1/2) | Plasma Decay half-life is the time measured for the concentration to decrease by one half. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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) | Radioactivity corresponds to 100 μCi [14C]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 | 
| Time to Reach Maximum Observed Plasma Radioactivity Concentration (Tmax) | Radioactivity corresponds to 100 μCi [14C]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 | 
| 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. | 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 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. | 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) 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| Maximum Observed Concentration of Radioactivity in Whole Blood (Cmax) | Radioactivity corresponds to 100 μCi [14C]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 | 
| 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. | 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 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. | 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 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. | 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) 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | 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 | 
| 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. | From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose | 
| 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. | 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 | 
| 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. | 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 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. | From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose | 
| 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiolabeled, healthy volunteers