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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-02341066
* Drug: PF-02341066
* Drug: PF-02341066


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 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

Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.0<br>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<br>* Cohort 1: a 150 mg single dose of PF-02341066 administered as 1 x 50 mg IRT and 1 x 100 mg IRT.<br>Drug: PF-02341066<br>* Cohort 2: a 250 mg single dose of PF-02341066 administered as 1 x 50 mg IRT and 2 x 100 mg IRTs.<br>Drug: PF-02341066<br>* Cohort 3: a 400 mg single dose of PF-02341066 administered as 4 x 100 mg IRTs.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PK profile in Japanese healthy male volunteers