Journal article
Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer
Cancer chemotherapy and pharmacology, Vol.85(3), pp.621-626
03/01/2020
DOI: 10.1007/s00280-020-04037-9
PMCID: PMC7036073
PMID: 32036412
Abstract
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(infinity)) 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.
Details
- Title: Subtitle
- Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer
- Creators
- Hani M. Babiker - University of ArizonaMohammed Milhem - University of IowaJoseph Aisner - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USAWilliam Edenfield - University of South CarolinaDale Shepard - Cleveland ClinicMichael Savona - Vanderbilt University Medical CenterSwaminathan Iyer - The University of Texas MD Anderson Cancer CenterMaen Abdelrahim - Methodist HospitalC. L. Beach - Summit (United Kingdom)Barry Skikne - Bristol-Myers Squibb (Switzerland)Eric Laille - Summit (United Kingdom)Kao-Tai Tsai - Summit (United Kingdom)Thai Ho - Mayo Clinic Hospital
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.85(3), pp.621-626
- DOI
- 10.1007/s00280-020-04037-9
- PMID
- 32036412
- PMCID
- PMC7036073
- NLM abbreviation
- Cancer Chemother Pharmacol
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Publisher
- Springer Nature
- Number of pages
- 6
- Grant note
- R01 CA224917 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 03/01/2020
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359878802771
Metrics
17 Record Views