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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: PF-02341066

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: March 5, 2010
• First Submitted That Met QC Criteria: March 5, 2010
• First Posted (Estimate): March 8, 2010

Study Record Updates

• Last Update Posted (Estimate): February 29, 2012
• Last Update Submitted That Met QC Criteria: February 28, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: healthy volunteers; radiolabeled
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Crizotinib
• Other Study ID Numbers: A8081009