This study will estimate the effect of food and the proton pump inhibitor, esomeprazole on the pharmacokinetics of crizotinib in a coated microsphere formulation.
This study is an open-label, randomized, 4-period, 5-treatment, 6-sequence study in adult healthy volunteers. Subjects will receive up to four separate single oral 300 mg doses of a coated microsphere (cMS) formulation of crizotinib. Period 1 through Period 3 will evaluate the effect of food, and, the effect of multiple doses of a gastrointestinal acid reducing agent, esomeprazole, in fasted state, on the pharmacokinetics (PK) of crizotinib cMS. Period 4 will evaluate whether apple sauce or orange juice may reduce the effect of multiple doses of esomeprazole on the PK of crizotinib cMS, if there is an effect.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
18
Crizotinib in a coated microsphere formulation
Proton pump inhibitor, esomeprazole
Pfizer New Haven Clinical Research Unit
New Haven, Connecticut, United States
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).
Time frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Maximum Observed Plasma Concentration (Cmax)
Time frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Time of last observed concentration (Tlast)
Time frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Apparent Oral Clearance (CL/F)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
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Time frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
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.
Time frame: Crizotinib pre-dose, 1, 2, 4, 6, 8, 10, 12, 24, 48, 96 hours post-dose
Number of Participants With Clinical Laboratory Abnormalities
Time frame: Baseline up to 35 calendar days after the last crizotinib dose
Number of Participants With Abnormal Electrocardiogram (ECG)
Time frame: Baseline up to 35 calendar days after the last crizotinib dose
Number of Adverse Events by Severity
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs are classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.
Time frame: Baseline up to 35 calendar days after the last crizotnib dose