Blood: Pharmacokinetics, Efficacy and Safety of Oral Cedazuridine/Tisitabin Therapeutics MDS and CMML

This study is a Phase 2 clinical trial designed to compare the exposure, demethylation activity and safety of the cedazuridine 100mg/Ditathabin 35mg and standard Sitabin 20mg/m2(IV) treatment for the first two courses of treatmentrecruited adult patients with high-risk myeloma hyperplasia syndrome (MDS) or chronic myeloid monocyte leukemia (CMML) and were assigned 1:1 at random to the oral cedazuridine/dixithadine group or IV,200-course exchange therapy;initially administered as separate capsules in the dose determination phase, cedazuridine and Dixithabin, and then administered as a single fixed dose combination (FDC) tabletMain endpoint: Average exposure levels in the tatrice, LINE-1 DNA demethylation percentage, and clinical response80 patients were treated in random groupsThe average exposure levelratio of oral and IV disalita-like in the dose determination and FDC stage was 93.5% and 97.6%, respectivelyThe difference between LINE-1 demethylation between the two groups was no more than 1%Forty-eight (60%) patients received clinical remission, of which 17 (21%) received full remissionthe most common stage 3 and above side effects were neusconotytic cell reduction (46%), platelet reduction (38%) and fevernent neutrophils decrease (29%)in summary, in the first two courses of treatment, oral cedazuridine/titabin (100/35mg) and IV sitabin 20mg/m2 can produce similar levels of geosythabin exposure and DNA demethylation, as well as similar safety and efficacy