Repeated supratherapeutic dosing of strontium ranelate over 15days does not prolong QT c interval in healthy volunteers

摘要

AIMS The study was performed to assess the safety of strontium ranelate in accordance with the ICH, E14 guidelines for QT/QT c studies. Its primary objective was to compare supratherapeutic repeated dosing of strontium ranelate (4gday -1 for 15days) with placebo on the largest time-matched mean QT c variation, from baseline to under treatment values, in healthy subjects. METHODS Ninety-six healthy male and female subjects (27.7 ± 7.5years) were included to receive 1day of placebo followed by 15days of supratherapeutic repeated dosing of strontium ranelate (4gday -1), in a 4month, randomized, placebo (16days) and positive-controlled (single dose of moxifloxacin 400mg preceded by 15days of placebo), double-blind, double dummy, crossover design. Measurement of QT interval was performed automatically on the ECGs with subsequent manual onscreen over-reading by cardiologists using electronic callipers. RESULTS The largest time-matched difference in QT cI (individual QT correction for heart rate) between moxifloxacin 400mg and placebo was observed at 2h post dose (mean [95% CI] 10.62 [7.90, 13.35] ms). For strontium ranelate (4gday -1) the largest time-matched difference in QT cI compared with placebo was observed at 1h post dose (mean [90% CI] 7.54 [5.17, 9.90] ms). No subject had a QT c greater than 480ms during the study. Both moxifloxacin and strontium ranelate were well tolerated in healthy subjects. CONCLUSIONS The findings of this study demonstrate that the administration of supratherapeutic repeated oral doses of strontium ranelate (4gday -1 for 15days) does not lead to a prolongation of the QT/QT c interval above the threshold of regulatory concern.