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Crizotinib is a small‐molecule, multitargeted tyrosine kinase inhibitor that exhibits decreased aqueous solubility at a higher pH. This open‐label, randomized, phase 1 study (NCT01549574) evaluated the effect of multiple doses of the proton pump inhibitor esomeprazole on the pharmacokinetics (PK) of crizotinib and the safety of crizotinib with or without esomeprazole in healthy adults. Participants received a single 250‐mg crizotinib dose after overnight fast or a single 250‐mg crizotinib dose following esomeprazole 40 mg/day for 5 days. After a washout of ≥14 days, participants crossed over to the alternate treatment. Blood samples for plasma analysis were taken up to 144 hours after crizotinib dosing and relevant PK parameters estimated. Safety was assessed in all participants receiving ≥1 dose of study medication. Fifteen participants were evaluable for PK and safety for each treatment. Coadministration with esomeprazole resulted in a slight decrease (≈10%) in the crizotinib geometric mean area under the plasma concentration–time profile from time 0 to infinity (adjusted geometric mean ratio, 89.81% [90% confidence interval, 79.05‐102.03]). Coadministration of esomeprazole did not affect peak crizotinib exposure. Adverse events (AEs) occurred in similar numbers between treatments; no serious or severe AEs occurred. The most common AE was diarrhea. Although esomeprazole decreased total exposure of crizotinib, it is not considered clinically meaningful, and dose modification is not required when crizotinib is coadministered with agents that affect gastric pH.

Evaluation of Proton Pump Inhibitor Esomeprazole on Crizotinib Pharmacokinetics in Healthy Participants