A drug-drug interaction study to assess the potential effect of acid-reducing agent, lansoprazole, on quizartinib pharmacokinetics.

Quizartinib, a potent, selective FMS-like tyrosine kinase 3 (FLT3) inhibitor, is currently in phase 3 development for patients with FLT3-internal tandem duplication-mutated acute myeloid leukemia (AML). Acid-reducing agents (ARAs; e.g., proton pump inhibitors) are frequently used during AML treatment. Since quizartinib demonstrates pH-dependent solubility, the effect of lansoprazole coadministration on pharmacokinetics (PK) of quizartinib tablet formulation was assessed. An open-label, parallel-group study randomized 64 healthy adults to single-dose quizartinib 30 mg alone (reference) or lansoprazole (60 mg once daily, days 1-5) + single-dose quizartinib 30 mg (day 5) (test). Plasma concentrations of quizartinib and its active metabolite, AC886, were measured to 504 h postdose; the effect of lansoprazole on quizartinib PK was assessed by analysis of variance. Quizartinib geometric mean ratios (test/reference) and 90% confidence intervals for maximum observed plasma concentration (C Concomitant lansoprazole had minimal effect on quizartinib PK as a formulated tablet, indicating that quizartinib can be administered with ARAs.