Effect of Single Doses of HX0507 on QTc Intervals in Healthy People: a Phase Ⅰ Safety and Tolerability Study

【Abstract】 Objective To assess the effect of HX0507 on QTc interval in healthy people in a phaseⅠsafety and tolerability study. Methods Eighty healthy people were randomly assigned to one of the 13 dosage groups. Standard 12-lead ECGs data were collected before and after HX0507, a water soluble prodrug of propofol, was given intravenously to the participants (at 33 time points). The QT interval values were corrected for heart rate using Fridericia’s formula (QTcF=QT/RR0.33) and Bazett’s formula (QTcB=QT/RR0.5). The primary target variable was baseline-adjusted changes in QTcF (ΔQTcF). Results Prolongation of QT interval was induced by HX0507 administered at an anticipated clinical dosage （3 mg/kg） or at a stronger dosage （8 mg/kg ）and above. The mean ΔQTcF ranged from 5.61 ms to 32.24 ms, with an upper limit of 90% CI ranging from 10.30 ms to 53.90 ms. There was a linear correlation between HX0507 dosage and its effect on QT interval. Eight types of ECG-related adverse events were detected in 32 subjects. Conclusion Single administration of HX0507 induces dose-related QT prolongation.