Evaluation of the effect of food on the pharmacokinetics of axitinib in healthy volunteers

Abstract

To evaluate the effect of food on axitinib pharmacokinetics in healthy volunteers with two different crystal polymorphs. Two separate open-label, randomized, single-dose, three-period, crossover trials were conducted. Study I, conducted first using 5-mg axitinib Form IV film-coated immediate-release (FCIR) tablets, enrolled 18 subjects to compare fed versus fasted states and 24 subjects to evaluate the effect of timing of food consumption on axitinib pharmacokinetics. Study II enrolled 30 subjects to assess the effect of food using 5-mg axitinib Form XLI FCIR tablets. Subjects received axitinib after overnight fasting, with limited fasting or, depending on the study design, after consuming high-fat, high-calorie or moderate-fat, standard-calorie meals. For Form IV FCIR, compared with overnight fasting, axitinib plasma exposure [area under the concentration curve (AUC)] was decreased 23 % when administered with food. For Form XLI FCIR, mean axitinib plasma AUC and maximum plasma concentration (C(max)) were 19 and 11 % higher, respectively, with a high-fat, high-calorie meal compared with overnight fasting. When Form XLI FCIR was administered with moderate-fat, standard-calorie meal, AUC and C(max) were 10 and 16 % lower compared with overnight fasting. Both formulations were well tolerated. Adverse events, mostly gastrointestinal (7 % with Form IV FCIR and 13 % with Form XLI FCIR), were mild to moderate in both studies. While axitinib Form IV FCIR was associated with higher plasma exposure after overnight fasting, axitinib Form XLI FCIR can be administered with or without food as differences in axitinib pharmacokinetics under the two conditions were not clinically meaningful.