Relative Bioavailability Of A Crizotinib Oral Liquid Formulation To Crizotinib Formulated Capsule

Healthy Clinical Trial

Official title:

A Phase 1, Open-Label, Single Dose, Randomized, Cross-Over Relative Bioavailability Study Comparing An Oral Liquid Formulation To A Formulated Capsule Of Crizotinib (PF 02341066) In Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01297595
• Other study ID #: A8081019
• Status: Completed
• Phase: Phase 1
• First received: February 15, 2011
• Last updated: February 15, 2012
• Start date: March 2011
• Est. completion date: April 2011

Study information

• Verified date: February 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will be an open-label, randomized, 2-period, 2-treatment, 2-sequence, cross-over single-dose study employing administration of two oral formulations of crizotinib (OLF and FC) in the fasted state to healthy adult subjects. Twenty-two (22) subjects will be enrolled to obtain at least 20 evaluable subjects who complete the study. Each subject will receive two treatments (A and B) with a washout period of at least 14 days between each treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy male and/or female 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 or 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:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

• Any condition possibly affecting drug absorption (eg, gastrectomy).

• A positive urine drug screen.

• History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.

• Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication.

• 12-lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.

• Pregnant or nursing females; females of childbearing potential, including those with tubal ligation.

• Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Herbal supplements and hormonal replacement therapy must be discontinued 28 days prior to the first dose of study medication. As an exception, acetaminophen/paracetamol may be used at doses of =1 g/day. Limited use of non-prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor.

• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing.

• History of sensitivity to heparin or heparin-induced thrombocytopenia.

• Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.

• Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.

• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

• A positive serology for Hepatitis B or Hepatitis C.

• Subjects who currently smoke.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• crizotinib
Each subject will receive 250 mg single oral doses of oral liquid formulation and formulated capsule of crizotinib separated by at least 14 days.

Locations

Country	Name	City	State
Belgium	Pfizer Investigational Site	Bruxelles

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Curve From Time Zero to Infinite Time [AUC (0 - 8)]	AUC (0 - 8) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hours (hrs) post crizotinib dose	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast).	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Maximum Observed Plasma Concentration (Cmax)		0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Plasma Terminal Half-Life (t1/2)	Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half.	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Apparent Oral Clearance (CL/F)	Drug clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the plasma. Clearance obtained after oral dose (apparent oral clearance [CL/F]) is influenced by the fraction of the dose absorbed (F).	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Apparent Volume of Distribution (Vz/F)	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 plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182)	Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of Crizotinib metabolite (PF-06260182).	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Area Under the Curve From Time Zero to Infinite Time [AUC (0 - 8)] for Crizotinib Metabolite (PF-06260182)	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8) of crizotinib metabolite (PF-06260182).	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)		0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182)		0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Metabolite to Parent Ratio of Maximum Observed Plasma Concentration (MRCmax)	Metabolite (PF-06260182) to parent (crizotinib) molar ratio of maximum observed plasma concentration (MRCmax).	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration (MRAUClast)	Molar ratio of metabolite to parent area under the plasma concentration time-curve from time zero (pre-dose) to the last measured concentration (MRAUClast).	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No
Secondary	Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Infinite Time [MRAUC (0- 8)]	Molar ratio of metabolite to parent area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0- 8) [MRAUC (0- 8)].	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose	No

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