Randomized phase 1 crossover study assessing the bioequivalence of capsule and tablet formulations of dovitinib (TKI258) in patients with advanced solid tumors.

Abstract

A capsule formulation of the tyrosine kinase inhibitor dovitinib (TKI258) was recently studied in a phase 3 renal cell carcinoma trial; however, tablets are the planned commercial formulation. Therefore, this randomized 2-way crossover study evaluated the bioequivalence of dovitinib tablet and capsule formulations in pretreated patients with advanced solid tumors, excluding breast cancer. In this 2-part study, eligible patients received dovitinib 500mg once daily on a 5-days-on/2-days-off schedule. During the 2-period bioequivalence phase, patients received their initial formulation (capsule or tablet) for 3weeks before being switched to the alternative formulation in the second period. Patients could continue to receive dovitinib capsules on the same dosing schedule during the post-bioequivalence phase. A total of 173 patients were enrolled into the bioequivalence phase of the study (capsule→tablet, n=88; tablet→capsule, n=85), and 69 patients had evaluable pharmacokinetics (PK) for both periods. PK analyses showed similar exposure and PK profiles for the dovitinib capsule and tablet formulations and supported bioequivalence [geometric mean ratios: AUClast, 0.95 (90% CI 0.88-1.01); C max, 0.98 (90% CI 0.91-1.05)]. The most common adverse events, suspected to be study drug related, included diarrhea (60%), nausea (53%), fatigue (45%), and vomiting (43%). Of 168 patients evaluable for response, 1 achieved a partial response, and stable disease was observed in 32% of patients. Dovitinib capsules and tablets were bioequivalent, with a safety profile similar to that observed in other dovitinib studies of patients with heavily pretreated advanced solid tumors.