Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer

PURPOSE: CC-486 is an oral formulation of azacitidine that allows for extended dosing schedules to prolong azacitidine exposure to malignant cells and maximize clinical activity. CC-486 300 mg daily, administered for 14 or 21 days of 28-day treatment cycles, is currently under investigation in two ongoing phase III trials. The 300-mg daily dose in these studies is administered as two 150-mg tablets (Formulation A). METHODS: We evaluated the bioequivalence of one 300-mg CC-486 tablet (Formulation B) with Formulation A and food effect on Formulation B, in adult patients with cancer in a 2-stage crossover design study. RESULTS: The ratios of the geometric means of the maximum azacitidine plasma concentration (C(max)) and of the area under the plasma concentration–time curve from time 0 extrapolated to infinity (AUC(∞)) were 101.5% and 105.7%, demonstrating the bioequivalence of Formulations A and B. Formulation B was rapidly absorbed under fasted and fed conditions. The geometric mean of C(max) was significantly decreased by ~ 21% in the fed state. Median T(max) was reached at 2 h and 1 h post-dose in fed and fasted states, respectively (P < 0.001). Nevertheless, systemic drug exposure (AUC) in fed and fasted states was within the 80–125% boundaries of bioequivalence and differences in C(max) and T(max) are not expected to have a clinical impact. CONCLUSION: The single 300-mg CC-486 tablet was bioequivalent to two 150-mg tablets, which have shown to be efficacious and generally well-tolerated in clinical trials, and can be taken with or without food. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00280-020-04037-9) contains supplementary material, which is available to authorized users.