• oral azacitidine;
  • CC-486;
  • pharmacokinetics;
  • formulation;
  • effect of food;
  • proton-pump inhibitor


Parenteral azacitidine improves overall survival in higher-risk myelodysplastic syndromes. An oral azacitidine formulation would allow extended dosing schedules, potentially improving safety and/or efficacy. Two Phase 1 studies evaluated the pharmacokinetics (PK) of oral azacitidine in subjects with hematologic malignancies. Study 1 evaluated different oral formulations (immediate release tablet [IRT], enteric-coated tablet, and capsule; N = 16). Study 2 assessed the effect of food (Part 1; N = 17) and gastric pH modulation with omeprazole (Part 2; N = 14) on oral azacitidine PK. Azacitidine plasma concentration–time profiles for IRT and capsule formulations were similar, with more rapid time to maximum plasma concentration (Tmax) than the enteric-coated tablet. Study 2 evaluated only IRT formulations of oral azacitidine. Under fed condition, Tmax was delayed ∼1.5 hours but area under the concentration–time curve (AUC) and maximum plasma concentrations (Cmax) were comparable under fed and fasted conditions. Mean azacitidine AUC and Cmax increased upon omeprazole co-administration (18.3% and 13.2%, respectively, vs. oral azacitidine alone), but not to a clinically meaningful extent. High inter-subject variability in AUC and Cmax (%CV range 46.4–68.9%) was observed. Oral azacitidine is rapidly absorbed with little or no effect of food on PK parameters, and does not require dose adjustments when taking a proton-pump inhibitor.