Bioequivalence And Food Effect Study Comparing The Commercial Formulation Of Crizotinib To Its Clinical Study Formulations And Commercial Formulation With Or Without Food In Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: crizotinib

• Registration Number: NCT01154218
• Lead Sponsor: Pfizer

Brief Summary

The purpose of this study is to demonstrate bioequivalence of the Commercial Image Capsule (CIC) relative to the Immediate Release Tablet (IRT) of crizotinib, bioequivalence of CIC relative to Powder in Capsule (PIC) of crizotinib, and lack of an effect of high fat meal on the pharmacokinetics (PK) of crizotinib when administered as CIC Formulation in healthy volunteers.

Detailed Description

The purpose of this study is to demonstrate bioequivalence of the CIC relative to IRT and CIC relative to PIC, and lack of an effect of food on the PK of crizotinib in healthy volunteers.

Study Timeline

• Study First Submitted: 2010-06-29
• Study First Submitted QC: 2010-06-29
• Study First Posted: 2010-06-30
• Study Start: 2010-08
• Primary Completion: 2010-11
• Study Completion: 2010-11
• Results First Submitted: 2011-09-12
• Results First Submitted QC: 2011-09-12
• Status Verified: 2011-10
• Results First Posted: 2011-10-19
• Last Update Submitted: 2011-10-20
• Last Update Posted: 2011-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• Healthy male and/or female of non-childbearing potential 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

• Subjects who are smoking, or with evidence of disease, conditions affecting absorption, treatment with other investigational drug within 30 days, history of regular alcohol consumption, use of prescription, nonprescription drugs and dietary supplement within 7 days, or blood donation of 500 mL within 56 days.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	crizotinib	All subjects will receive four treatments in one of the indicated orders: A-B-C-D, B-D-A-C, C-A-D-B, D-C-B-A

Primary Outcome Measures

Name	Time	Method
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞])	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hours (hrs) post crizotinib dose	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-∞).
Maximum Observed Plasma Concentration (Cmax)	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose

Secondary Outcome Measures

Name	Time	Method
Apparent Volume of Distribution (Vz/F)	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose	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 (Vz/F) is influenced by the fraction absorbed.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182)	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose	Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of Crizotinib metabolite (PF-06260182).
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose	Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast).
Apparent Oral Clearance (CL/F)	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose	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.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182)	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Plasma Decay Half Life (t1/2)	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182)	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose	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-∞).
Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇧🇪 Bruxelles, Belgium