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

ABSTRACT

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 (AUClast; 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 AUClast and an 18% decrease for C max. Comparison of LF meal versus NM showed a 1% decrease for AUClast 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.