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Randomized Controlled Trial
. 2020 Feb;9(2):277-286.
doi: 10.1002/cpdd.770. Epub 2020 Jan 8.

Effect of Food on the Pharmacokinetics of Quizartinib

Jianke Li  1 , Melissa Holmes  1 , Martin Kankam  2 , Denise Trone  1 , Jeanne Mendell  3 , Guy Gammon  1
Affiliations
Randomized Controlled Trial

Effect of Food on the Pharmacokinetics of Quizartinib

Jianke Li et al. Clin Pharmacol Drug Dev. 2020 Feb.

Abstract

Quizartinib is an oral, highly potent, and selective type II FMS-like tyrosine kinase 3 inhibitor in development for acute myeloid leukemia. This parallel-group study evaluated potential food effects on quizartinib absorption in healthy subjects who received a single 30-mg dose after overnight fasting (n = 34) or a high-fat, high-calorie meal (n = 30). Blood samples were collected through 504 hours after dosing, and pharmacokinetic parameters calculated were maximum observed concentration (Cmax ) and area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast ) and from time 0 to infinity (AUCinf ). Mean quizartinib pharmacokinetic profiles were similar under fasted and fed conditions. The geometric least squares means ratios (%) for fed/fasted and associated 90% confidence intervals (CIs) for Cmax , AUClast , and AUCinf were 91.58 (82.15-102.08), 105.39 (90.79-122.35), and 108.39 (91.54-128.34), respectively. The 90%CI for the ratio fell within the 80% to 125% limits for Cmax and AUClast , with 90%CI for AUCinf slightly outside the limits (ie, 128%). Food delayed quizartinib time to Cmax by 2 hours. All adverse events were either mild or moderate; no discontinuations due to adverse events occurred. Based on these results, quizartinib can be administered without regard to food.

Keywords: AML; FLT3; TKI; food effect; quizartinib.

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Conflict of interest statement

J.L. and M.H. were employees of Daiichi Sankyo, Inc. and Ambit Biosciences at the time this study was conducted. J.M. is an employee of Daiichi Sankyo, Inc. D.T. was an employee of Daiichi Sankyo, Inc. and Ambit Biosciences at the time this study was conducted. G.G. was an employee of Daiichi Sankyo, Inc. at the time this study was conducted and has received stock or other ownership in and travel/accommodations/expenses from Daiichi Sankyo. M.K. has no conflicts to disclose.

Figures

Figure 1
Figure 1
Study flowchart.
Figure 2
Figure 2
Mean (standard deviation) plasma quizartinib concentration–time profiles after administration of 30‐mg quizartinib tablet under fasted or fed conditions on linear (A) and semilogarithmic (B) scales.
Figure 3
Figure 3
Mean (standard deviation) plasma AC886 concentration–time profiles after administration of 30‐mg quizartinib tablet under fasted or fed conditions on linear (A) and semilogarithmic (B) scales.
See this image and copyright information in PMC

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