A Study In Japanese Healthy Male Volunteers To Investigate The Safety, Tolerability And Pharmacokinetics Of PF-02341066

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01250730
First received: November 17, 2010
Last updated: October 20, 2011
Last verified: October 2011
  Purpose

The purpose of this study is to investigate the pharmacokinetics of single doses of PF-02341066 (150, 250, and 400 mg) in the fasted condition in Japanese healthy male volunteers.


Condition Intervention Phase
Healthy
Drug: PF-02341066
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Phase 1, Open Label, Dose Escalation, Single Oral Dose Study In Japanese Healthy Male Volunteers To Investigate The Safety, Tolerability And Pharmacokinetics Of PF-02341066

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] of Crizotinib [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]

    AUC(0-inf) of crizotinib is estimated from the crizotinib concentration. It is obtained from AUClast plus (Clast/kel).

    AUClast = area under the plasma concentration-time curve from zero time until the last measurable concentration.

    Clast = the last quantifiable concentration. Kel = terminal phase elimination rate constant.


  • Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Crizotinib [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
    AUClast of crizotinib is estimated from the crizotinib concentration. It is obtained from Linear/Log trapezoidal method.

  • Maximum Plasma Concentration (Cmax) of Crizotinib [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
  • Time to Cmax (Tmax) of Crizotinib [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
  • Terminal Elimination Half-life (t1/2) of Crizotinib [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]

    t1/2 of crizotinib is the time measured for the plasma concentration to decrease by one half. It is obtained from a Loge(2)/kel.

    Kel = terminal phase elimination rate constant


  • Apparent Oral Clearance (CL/F) of Crizotinib [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
    CL/F of crizotinib is obtained from a Dose per AUCinf.

  • Apparent Volume of Distribution (Vz/F) of Crizotinib [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]

    Vz/F of crizotinib is obtained from a Dose / (AUCinf *kel).

    Kel = terminal phase elimination rate constant


  • Dose Normalized AUC(0-inf) of Crizotinib [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
    Dose normalized (to 150 mg dose) AUC(0-inf) is obtained from AUC(0-inf) / (Dose/150).

  • Dose Normalized AUClast of Crizotinib [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
    Dose normalized (to 150 mg dose) AUClast is obtained from AUClast / (Dose/150).

  • Dose Normalized Cmax of Crizotinib [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
    Dose normalized (to 150 mg dose) Cmax is obtained from Cmax / (Dose/150).

  • Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUC0-inf) of Plasma Active Metabolite (PF-06260182) [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]

    AUC(0-inf) of PF-06260182 is estimated from the PF-06260182 concentration. It is obtained from AUClast plus (Clast/kel).

    AUClast = area under the plasma concentration-time curve from zero time until the last measurable concentration.

    Clast = the last quantifiable concentration. Kel = terminal phase elimination rate constant.


  • Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Plasma Active Metabolite (PF-06260182) [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
    AUClast of crizotinib is estimated from the crizotinib concentration. It is obtained from Linear/Log trapezoidal method.

  • Maximum Plasma Concentration (Cmax) of Plasma Active Metabolite (PF-06260182) [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
  • Time to Cmax (Tmax) of Plasma Active Metabolite (PF-06260182) [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
  • Metabolite to Parent Ratio AUC(0-inf) [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
    The metabolic ratio (MR) is calculated by first converting the AUC(0-inf) for both crizotinib and metabolite (PF-06260182) from mass units to molar units.

  • Metabolite to Parent Ratio AUClast [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
    The metabolic ratio (MR) is calculated by first converting the AUClast for both crizotinib and metabolite (PF-06260182) from mass units to molar units.

  • Metabolite to Parent Ratio Cmax [ Time Frame: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose ] [ Designated as safety issue: No ]
    The metabolic ratio (MR) is calculated by first converting the Cmax for both crizotinib and metabolite (PF-06260182) from mass units to molar units.


Enrollment: 18
Study Start Date: December 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1.0
This study will consist of three cohorts: PF-02341066 150 mg treatment group (n = 6), PF-02341066 250 mg treatment group (n = 6) and PF-02341066 400 mg treatment group (n = 6).
Drug: PF-02341066
Cohort 1: a 150 mg single dose of PF-02341066 administered as 1 x 50 mg IRT and 1 x 100 mg IRT.
Other Name: Not Specified
Drug: PF-02341066
Cohort 2: a 250 mg single dose of PF-02341066 administered as 1 x 50 mg IRT and 2 x 100 mg IRTs.
Other Name: Not Specified
Drug: PF-02341066
Cohort 3: a 400 mg single dose of PF-02341066 administered as 4 x 100 mg IRTs.
Other Name: Not Specified

Detailed Description:

The purpose of this study is to investigate the pharmacokinetics of single doses of PF-02341066 (150, 250, and 400 mg) in the fasted condition in Japanese healthy male volunteers.

  Eligibility

Ages Eligible for Study:   20 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male subjects, 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/m2; and a total body weight >50 kg

Exclusion Criteria:

  • Subjects who are smoking,
  • Subjects with evidence of disease,
  • Subjects with conditions affecting absorption,
  • Subjects with treatment with other investigational drug within 30 days,
  • Subjects with history of regular alcohol consumption,
  • Subjects with use of prescription, nonprescription drugs and dietary supplement within 28 days,
  • Subjects with blood donation of approximately 400 mL within 3 months or 200 mL within 1 month prior to dosing
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01250730

Locations
Japan
Pfizer Investigational Site
Hachioji-shi, Tokyo, Japan
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: NCT01250730     History of Changes
Other Study ID Numbers: A8081022
Study First Received: November 17, 2010
Results First Received: October 20, 2011
Last Updated: October 20, 2011
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Pfizer:
PK profile in Japanese healthy male volunteers

ClinicalTrials.gov processed this record on April 15, 2014