Compliance and clinical benefit of deferasirox granule and dispersible tablet formulation in pediatric patients with transfusional iron overload: in a randomized, open-label, multicenter, phase II study

Abstract

CALYPSO (NCT02435212), a randomized, open-label, multicenter, phase 2 study evaluated the compliance, clinical benefits, and safety of deferasirox granules and dispersible tablets in pediatric patients with iron overload. Iron chelation therapy-naive and iron chelation therapy–pre-treated patients aged 2 to <18 years with transfusiondependent anemias were enrolled. Patients were randomized 1:1 to deferasirox granules or dispersible tablets for 48 weeks, stratified by age group and prior iron chelation therapy. In this study, the co-primary objectives are to evaluate compliance and change from baseline in serum ferritin after 24 weeks for both formulations in iron chelation therapy-naive patients. In total, 224 patients, mostly with β-thalassemia major (63.4%), were randomized to granules (n=112) or dispersible tablets (n=112). Primary analysis was conducted when 96 iron chelation therapy-naive patients had completed 24 weeks of treatment/discontinued early; least squares mean (LSM) compliance in the deferasirox granules and dispersible tablets groups, was 86.8% and 84.3% (difference 2.6%; P=0.360) respectively, while least squares mean change from baseline in serum ferritin was +4.8 and −171.5 ng/mL (difference: 176.4 ng/mL; P=0.255). Slight differences were observed in the observer/patient-reported outcome scores between the granules and dispersible tablet groups and the overall scores indicate good adherence, satisfaction/preference, fewer concerns and good palatability with both deferasirox formulations. Safety analyses (n=221) found that the most frequently observed adverse events (granules and dispersible tablets) were increased urine protein/creatinine ratio (>0.5 mg/mg; 24.5% and 34.2%), upper respiratory tract infection (28.2% and 29.7%), and pyrexia (26.4% and 23.4%).

In iron chelation therapy-naive patients, mean compliance and change from baseline in serum ferritin with both deferasirox formulations were not significantly different. The safety profile was comparable between granule and dispersible tablets formulations, and was consistent with the general safety profile of deferasirox.