The primary purpose of the study is to estimate the relative bioavailability and palatability of 2 new crizotinib formulations to the commercially available crizotinib formulated capsule at a 250 mg dose administered under fasted conditions in adult healthy participants. Additionally, this study aims to assess the safety and tolerability of crizotinib 250 mg single dose in 4 formulations when given fasted, with high fat meal, or with a proton pump inhibitor in healthy participants. Finally, this study will explore the effect of food or proton pump inhibitor on the pharmacokinetics of the 2 new crizotinib formulations. We hypothesize 1 of the 2 new crizotinib formulations will have improved relative bioavailability and palatability than the formulated capsule under fasted or fed conditions with or without a proton pump inhibitor.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
25
Single 250 mg crizotinib dose as coated microsphere 1 (cMS1) formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.
A single 250 mg crizotinib dose as coated microsphere 2 (cMS2) formulation will be administered on the morning of Day 1 after overnight fast of at least 10 hours.
A single 250 mg crizotinib dose as FC formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.
A single 250 mg crizotinib dose as OS will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.
250 mg crizotinib as cMS1 formulation will be administered with high-fat, high-calorie meal after an overnight fast of at least 10 hours.
250 mg crizotinib as cMS2 will be administered with a high-fat, high-calorie meal after an overnight fast of at least 10 hours.
40 mg esomeprazole will be administered 1 hour prior to dinner on Day -5 through Day -1. A single 250 mg crizotinib dose as cMS1 formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.
40 mg esomeprazole will be administered 1 hour prior to dinner on Day -5 through Day -1. A single 250 mg crizotinib dose as cMS2 formulation will be administered on the morning of Day 1 after an overnight fast of at least 10 hours.
Pfizer New Haven Clinical Research Unit
New Haven, Connecticut, United States
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
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 - ∞).
Time frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, and 96 hours post-dose in Periods 1, 2, 3, 5, and 6.
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: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, and 96 hours post-dose in Periods 1, 2, 3, 5, and 6.
Maximum Observed Plasma Concentration (Cmax)
Maximum observed plasma concentration.
Time frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, and 96 hours post-dose in Periods 1, 2, 3, 5, and 6.
Number of subjects reporting overall liking of drug formulation
Overall liking assesses the degree that a participant likes a drug formulation based on sensory attributes experienced by the participant after tasting a product. It is scored based on a measurement of taste questionnaire.
Time frame: 1 (immediately after dosing), 5, 10, and 20 minutes after crizotinib administration in Treatments A, B and D.
Number of subjects reporting bitterness of drug formulation
Bitterness assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire.
Time frame: 1 (immediately after dosing), 5, 10, and 20 minutes after crizotinib administration in Treatments A, B and D.
Number of subjects reporting mouth feel from drug formulation
Mouth feel assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire.
Time frame: 1 (immediately after dosing), 5, 10, and 20 minutes after crizotinib administration in Treatments A, B and D.
Number of subjects reporting tongue/mouth burn from drug formulation
Tongue/mouth burn assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire.
Time frame: 1 (immediately after dosing), 5, 10, and 20 minutes after crizotinib administration in Treatments A, B and D.
Number of subjects reporting throat burn from drug formulation
Throat burn assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire.
Time frame: 1 (immediately after dosing), 5, 10, and 20 minutes after crizotinib administration in Treatments A, B and D.
Percentage of subjects reporting overall liking of drug formulation
Overall liking assesses the degree that a participant likes a drug formulation based on sensory attributes experienced by the participant after tasting a product. It is scored based on a measurement of taste questionnaire.
Time frame: 1 (immediately after dosing), 5, 10, and 20 minutes after crizotinib administration in Treatments A, B and D.
Percentage of subjects reporting bitterness of drug formulation
Bitterness assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire.
Time frame: 1 (immediately after dosing), 5, 10, and 20 minutes after crizotinib administration in Treatments A, B and D.
Percentage of subjects reporting mouth feel from drug formulation
Mouth feel assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire.
Time frame: 1 (immediately after dosing), 5, 10, and 20 minutes after crizotinib administration in Treatments A, B and D.
Percentage of subjects reporting tongue/mouth burn from drug formulation
Tongue/mouth burn assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire.
Time frame: 1 (immediately after dosing), 5, 10, and 20 minutes after crizotinib administration in Treatments A, B and D.
Percentage of subjects reporting throat burn from drug formulation
Throat burn assesses the degree that a participant experienced this sensory attribute after tasting a drug formulation. It is scored based on a measurement of taste questionnaire.
Time frame: 1 (immediately after dosing), 5, 10, and 20 minutes after crizotinib administration in Treatments A, B and D.
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