Repeated supratherapeutic dosing of strontium ranelate 4g/d over 15 days does not prolong QTc interval in healthy volunteers.

: Aims:? The study was performed to assess the safety of strontium ranelate in accordance with the ICH, E14 guidelines for QT/QTc studies. Its primary objective was to compare supratherapeutic repeated dosing of strontium ranelate (4g/day for 15 days) to placebo on the largest time-matched mean QTc variation, from baseline to under treatment values, in healthy subjects. Methods:? 96 healthy male and female subjects (27.7 ± 7.5 years) were included to receive 1 day of placebo followed by 15 days of supratherapeutic repeated dosing of strontium ranelate (4 g/day), in a 4-month, randomized, placebo (16 days) and positive-controlled (single dose of moxifloxacin 400 mg preceded by 15 days 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 QTcI (individual QT correction for heart rate) between moxifloxacin 400 mg and placebo was observed at 2 hours post-dose (mean [95%CI] 10.62 [7.90-13.35] msec). For strontium ranelate (4g/day) the largest time-matched difference in QTcI compared to placebo was observed at 1 hour post-dose (mean [90%]: 7.54 [5.17-9.90] msec). No subject had a QTc greater than 480 msec 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 (4g/day for 15 days) does not lead to a prolongation of the QT/QTc interval above the threshold of regulatory concern. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.