We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer.
- Authors
Babiker, Hani M.; Milhem, Mohammed; Aisner, Joseph; Edenfield, William; Shepard, Dale; Savona, Michael; Iyer, Swaminathan; Abdelrahim, Maen; Beach, C. L.; Skikne, Barry; Laille, Eric; Tsai, Kao-Tai; Ho, Thai
- Abstract
<bold>Purpose: </bold>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).<bold>Methods: </bold>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.<bold>Results: </bold>The ratios of the geometric means of the maximum azacitidine plasma concentration (Cmax) 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 Cmax was significantly decreased by ~ 21% in the fed state. Median Tmax 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 Cmax and Tmax are not expected to have a clinical impact.<bold>Conclusion: </bold>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.
- Subjects
BIOAVAILABILITY; AZACITIDINE; CANCER patients; CLINICAL trials
- Publication
Cancer Chemotherapy & Pharmacology, 2020, Vol 85, Issue 3, p621
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-020-04037-9