Randomized, Blinded, Placebo- and Positive-Controlled Crossover Study to Determine the Effect of Deferiprone on the QTc Interval in Healthy Subjects.

Abstract

This study evaluated whether deferiprone, an oral iron chelator, acts to prolong the QT interval. Fifty healthy volunteers received single doses of each of the following: therapeutic dose of deferiprone (33mg/kg), supratherapeutic dose (50mg/kg), placebo, or moxifloxacin, a positive control known to significantly prolong QT interval. Following each dose, subjects underwent cardiac monitoring, pharmacokinetics assessments, and safety assessments. Based on the QT interval obtained using the Fridericia correction for heart rate (QTcF), the upper bound of the 1-sided 95% confidence interval of the mean difference between deferiprone and placebo was <10 milliseconds (the threshold of concern defined by authorities) at all time points for both doses: maximum difference of 3.01milliseconds for the therapeutic dose and 5.23milliseconds for the supratherapeutic dose. The difference in dQTcF between moxifloxacin and placebo demonstrated that the study was adequately sensitive to detect a significant prolongation of QTcF. The concentration-response correlation analyses revealed some weak but statistically significant trends of increase in dQTcF and ddQTcF with increasing exposure to deferiprone, but these trends should have no clinical consequence even at the recommended maximum dosage. In conclusion, there was no clinically meaningful effect on QTc interval following single therapeutic or supratherapeutic doses of deferiprone.