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A1580
October 16, 2007
9:00 AM - 11:00 AM
Room Hall D, Area F,
Single IV Sugammadex Doses up to 32 mg/kg Are Not Associated with QT/QTc Prolongation
Pieter-Jan de Kam, Ph.D., Jacqueline van Kuijk, M.S., Jean Smeets, Ph.D., Torben Thomsen, M.D., Ph.D., Pierre Peeters, Ph.D.
Department of Clinical Pharmacology & Kinetics, NV Organon, Oss, Netherlands
Background: The selective relaxant binding agent (SRBA) sugammadex is a modified γ-cyclodextrin with a novel mechanism of action, reversing the effects of the steroidal neuromuscular blocking agents rocuronium and vecuronium by encapsulation. This thorough QT/QTc study evaluated the effect of sugammadex on the individually corrected QTc interval (QTcI).

Methods: In this double-blind, cross-over thorough QT/QTc study, 62 volunteers were randomized to single doses of 4.0 mg/kg sugammadex (therapeutic dose), 32.0 mg/kg sugammadex (supra-therapeutic dose), moxifloxacin (400 mg) or placebo. According to ICH-E14, a thorough QTc study is negative if assay sensitivity is demonstrated and the one-sided 95% upper confidence limit for the largest time-matched mean QTc difference compared with placebo is below the 10 msec margin.

Results: Assay sensitivity was demonstrated because the positive control moxifloxacin showed QTcI prolongations exceeding 10 msec compared with placebo. The table shows that for both 4.0 mg/kg and 32.0 mg/kg sugammadex QTcI prolongations are well below 10 msec. Trial medication was safe and well tolerated.

Conclusion: Treatment with single intravenous doses of therapeutic (4 mg/kg) and supra-therapeutic (32 mg/kg) sugammadex were not associated with QTc prolongation based on the criteria of the ICH-E14 guideline. Furthermore, trial medication was safe and well tolerated.[table1]

Anesthesiology 2007; 107: A1580
Treatment group
Sugammadex 4.0 mg/kgsugammadex 32.0 mg/kgMoxifloxacin 400mg
Largest time-matched mean QTcl difference to placebo (msec)1.82.818.6
One-sided 95% upper confidencw limit (msec)4.35.321.8