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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01250730

Enrollment

Registered

2010-12-01

Start date

2010-12-31

Completion date

2011-01-31

Last updated

2011-11-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

PK profile in Japanese healthy male volunteers

Brief summary

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

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.

Interventions

DRUGPF-02341066

Cohort 1: a 150 mg single dose of PF-02341066 administered as 1 x 50 mg IRT and 1 x 100 mg IRT.

Study design

Intervention model

PARALLEL

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

20 Years to 55 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] of Crizotinib	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	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	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	AUClast of crizotinib is estimated from the crizotinib concentration. It is obtained from Linear/Log trapezoidal method.
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	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	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	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	CL/F of crizotinib is obtained from a Dose per AUCinf.
Apparent Volume of Distribution (Vz/F) of Crizotinib	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	Vz/F of crizotinib is obtained from a Dose / (AUCinf \*kel). Kel = terminal phase elimination rate constant
Dose Normalized AUC(0-inf) of Crizotinib	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	Dose normalized (to 150 mg dose) AUC(0-inf) is obtained from AUC(0-inf) / (Dose/150).
Dose Normalized AUClast of Crizotinib	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	Dose normalized (to 150 mg dose) AUClast is obtained from AUClast / (Dose/150).
Dose Normalized Cmax of Crizotinib	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	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)	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	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)	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	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)	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)	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	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	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	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	0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose	The metabolic ratio (MR) is calculated by first converting the Cmax for both crizotinib and metabolite (PF-06260182) from mass units to molar units.

Countries

Japan

Participant flow

Pre-assignment details

Twelve healthy subjects were assigned to open-label crizotinib treatment in either the 150 mg cohort (6 subjects) or 250 mg cohort (6 subjects). After the completion of assessment of safety at both 150 mg and 250 mg cohorts, the 400 mg cohort, the highest dose level in this study, was started.

Participants by arm

Arm	Count
Crizotinib 150 mg A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	6
Crizotinib 250 mg A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	6
Crizotinib 400 mg A 400 mg single dose of crizotinib administered as four 100 mg IRTs.	6
Total	18

Baseline characteristics

Characteristic	Crizotinib 150 mg	Crizotinib 250 mg	Crizotinib 400 mg	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	6 Participants	6 Participants	6 Participants	18 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	6 Participants	6 Participants	6 Participants	18 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	2 / 6	0 / 6	1 / 6
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6