Published in:
01-04-2015 | Original Article
A randomized, crossover phase 1 study to assess the effects of formulation (capsule vs tablet) and meal consumption on the bioavailability of dovitinib (TKI258)
Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015
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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.