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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01154218
First received: June 29, 2010
Last updated: October 20, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: crizotinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Phase 1, Single Dose Bioequivalence And Food Effect Study In Healthy Volunteers Comparing The Commercial Image Capsules To The Immediate Release Tablets And Powder In Capsule Formulations Of Crizotinib (PF-02341066), And The Commercial Image Capsule In The Fasted To Fed State

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hours (hrs) post crizotinib dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast).

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ] [ Designated as safety issue: No ]
  • Plasma Decay Half Life (t1/2) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Apparent Oral Clearance (CL/F) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ] [ Designated as safety issue: No ]
    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.

  • Apparent Volume of Distribution (Vz/F) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ] [ Designated as safety issue: No ]
    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 Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: August 2010
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

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

Drug: crizotinib

Treatment A (Reference 1): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 50-mg IRT and 2 × 100-mg IRTs.

Treatment B (Reference 2): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 50-mg PIC and 2 × 100 mg PICs.

Treatment C (Test for BE, Reference for Food Effect): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 250-mg CIC.

Treatment D (Test High Fat): a 250 mg single dose of crizotinib administered with a high-fat meal as 1 × 250-mg CIC


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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01154218

Locations
Belgium
Pfizer Investigational Site
Bruxelles, Belgium, B-1070
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: NCT01154218     History of Changes
Other Study ID Numbers: A8081011
Study First Received: June 29, 2010
Results First Received: September 12, 2011
Last Updated: October 20, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
bioequivalence
food effect
pharmacokinetics
crizotinib

Additional relevant MeSH terms:
Crizotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014