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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01082380
First received: March 5, 2010
Last updated: February 28, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Healthy Volunteer
Drug: PF-02341066
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase One Open-Label Single-Radiolabeled Dose Study To Investigate The Absorption, Metabolism And Excretion Of [14C]PF-02341066 In Healthy Male Volunteers

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable 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 ] [ Designated as safety issue: No ]
    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 - ∞)] [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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(%)] [ 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 ] [ Designated as safety issue: No ]
  • Maximum Observed Concentration in Plasma Radioactivity (Cmax) [ 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 ] [ Designated as safety issue: No ]
    Radioactivity corresponds to 100 μCi [14C]PF-02341066.

  • Time to Reach Maximum Observed Plasma Radioactivity 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 ] [ Designated as safety issue: No ]
    Radioactivity corresponds to 100 μCi [14C]PF-02341066.

  • Area Under the Curve From Time Zero to Last Quantifiable Plasma Radioactivity 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 ] [ Designated as safety issue: No ]
    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 - ∞)] [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    Radioactivity corresponds to 100 μCi [14C]PF-02341066.

  • Time to Reach Maximum Observed Concentration (Tmax) of Radioactivity in Whole Blood [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Day 0 through pre-dose (Day1) and as passed through until up to 480 hrs post-dose ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 6
Study Start Date: March 2010
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: PF-02341066
oral suspension, single 250 mg dose of PF 02341066 containing approximately 100 µCi of [14C]PF 02341066
Other Name: crizotinib

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01082380

Locations
United States, Connecticut
Pfizer Investigational Site
New Haven, Connecticut, United States, 06511
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01082380     History of Changes
Other Study ID Numbers: A8081009
Study First Received: March 5, 2010
Results First Received: September 12, 2011
Last Updated: February 28, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
radiolabeled
healthy volunteers

Additional relevant MeSH terms:
Crizotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014