A randomized, crossover phase 1 study to assess the effects of formulation (capsule vs tablet) and meal consumption on the bioavailability of dovitinib (TKI258)

Purpose: This 2-arm crossover study compared the relative bioavailability of two dovitinib (TKI258) formulations [anhydrate clinical service form (CSF) capsule and monohydrate final market image (FMI) tablet; Arm 1] and determined the effect of food on dovitinib exposure (Arm 2). Methods: Patients with advanced solid tumors, excluding breast cancer, were enrolled in 1 of the 2 arms of the study. Patients in Arm 1 were randomized to a single 500-mg dose of CSF capsule or FMI tablet followed by 7 days of rest and 500 mg of the other formulation. Patients in Arm 2 received 300 mg of FMI tablet daily and were randomized to follow 1 of 6 meal sequences, each with 3 prandial conditions: low fat (LF), high fat (HF), or no meal (NM). Results: In Arm 1 (n = 21), 17 patients were evaluable. FMI tablet compared with CSF capsule showed only slight reductions in the adjusted geometric means for area under the plasma concentration-time curve (AUC_last; 3 %) and maximum plasma concentration (C _max; 1 %). In Arm 2 (n = 42), 19 patients were evaluable. HF meal versus NM showed a 9 % decrease in the adjusted geometric mean for AUC_last and an 18 % decrease for C _max. Comparison of LF meal versus NM showed a 1 % decrease for AUC_last and a 10 % decrease for C _max. Common adverse events suspected to be study drug related included vomiting, diarrhea, nausea, and fatigue. Conclusions: Dovitinib FMI tablet had similar systemic exposure to the CSF capsule and was not affected by food.