Levetiracetam Thorough QT Study: Lack of Pro-Arrhythmic Effect
Abstract number :
3.306;
Submission category :
7. Antiepileptic Drugs
Year :
2007
Submission ID :
8052
Source :
www.aesnet.org
Presentation date :
11/30/2007 12:00:00 AM
Published date :
Nov 29, 2007, 06:00 AM
Authors :
R. Hulhoven1, D. Rosillon1, W. Bridson2, E. Salas3, D. Chen3, S. Watanabe1, M. A. Meeus1, A. Stockis1
Rationale: The study objective was to determine whether levetiracetam (LEV) has a threshold pharmacological effect on cardiac repolarization, as detected by QT interval prolongation in a thorough QT study.Methods: Single oral doses of placebo, 1000 mg LEV (therapeutic dose), 5000 mg LEV (supra-therapeutic dose), and 400 mg moxifloxacin (MOX; positive control) were randomly administered in a 4-way crossover to 52 healthy male and female subjects. Continuous 12-lead ECG was recorded during 24 h at baseline and following each treatment, using the Mortara Holter-device. Plasma samples were obtained pre-dose, and 0.5, 1, 1.5, 2, 4, 6, 12 and 24 h post-dose, for drug determination. Triplicate ECGs were extracted before each blood sampling and read centrally in a blinded manner. QT was corrected for heart rate using a gender- and study-specific correction (QTcSS). The primary endpoint was the largest time-matched mean difference of QTcSS change from baseline between drug and placebo (max.ΔΔQTcSS).Results: Mean max.ΔΔQTcSS for 1000 mg LEV, 5000 mg LEV and MOX was 4.0 ms, 4.1 ms and 7.7 ms, respectively. The upper limit of the 95% CI for 1000 mg and 5000 mg LEV was 8.0 ms and 8.1 ms, respectively; the lower limit of the 95% CI for MOX was 3.7 ms. After LEV, no QTcSS interval >480 ms, or change from baseline >60 ms, was observed. No particular safety concern was observed during the study.Conclusions: This thorough QT study is valid and demonstrates the absence of effects of LEV on cardiac repolarization. UCB funded
Antiepileptic Drugs