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

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

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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Hachioji-shi, Tokyo, Japan
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.; 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.; Drug: PF-02341066; Cohort 3: a 400 mg single dose of PF-02341066 administered as 4 x 100 mg IRTs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] of Crizotinib	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.	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Crizotinib	AUClast of crizotinib is estimated from the crizotinib concentration. It is obtained from Linear/Log trapezoidal method.	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Maximum Plasma Concentration (Cmax) of Crizotinib		0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Time to Cmax (Tmax) of Crizotinib		0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Terminal Elimination Half-life (t1/2) of Crizotinib	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	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Apparent Oral Clearance (CL/F) of Crizotinib	CL/F of crizotinib is obtained from a Dose per AUCinf.	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Apparent Volume of Distribution (Vz/F) of Crizotinib	Vz/F of crizotinib is obtained from a Dose / (AUCinf *kel). Kel = terminal phase elimination rate constant	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Dose Normalized AUC(0-inf) of Crizotinib	Dose normalized (to 150 mg dose) AUC(0-inf) is obtained from AUC(0-inf) / (Dose/150).	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Dose Normalized AUClast of Crizotinib	Dose normalized (to 150 mg dose) AUClast is obtained from AUClast / (Dose/150).	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Dose Normalized Cmax of Crizotinib	Dose normalized (to 150 mg dose) Cmax is obtained from Cmax / (Dose/150).	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUC0-inf) of Plasma Active Metabolite (PF-06260182)	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.	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
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)	AUClast of crizotinib is estimated from the crizotinib concentration. It is obtained from Linear/Log trapezoidal method.	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Maximum Plasma Concentration (Cmax) of Plasma Active Metabolite (PF-06260182)		0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Time to Cmax (Tmax) of Plasma Active Metabolite (PF-06260182)		0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Metabolite to Parent Ratio AUC(0-inf)	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.	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Metabolite to Parent Ratio AUClast	The metabolic ratio (MR) is calculated by first converting the AUClast for both crizotinib and metabolite (PF-06260182) from mass units to molar units.	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
Metabolite to Parent Ratio Cmax	The metabolic ratio (MR) is calculated by first converting the Cmax for both crizotinib and metabolite (PF-06260182) from mass units to molar units.	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours 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: December 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: November 17, 2010
• First Submitted That Met QC Criteria: November 29, 2010
• First Posted (Estimate): December 1, 2010

Study Record Updates

• Last Update Posted (Estimate): November 29, 2011
• Last Update Submitted That Met QC Criteria: October 20, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: PK profile in Japanese healthy male volunteers
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Crizotinib
• Other Study ID Numbers: A8081022