Abstracts

Rationale: To compare the efficacy and safety of topiramate (sprinkle capsules or oral liquid) with placebo as adjunct to other antiepileptic drugs (AEDs) in reducing refractory partial onset seizure (POS) rates in infants. Methods: This double-blind, international study was conducted from September 2005 - June 2007. Patients (N = 149) with clinical or EEG evidence of refractory POS were randomized (1:1:1:1) to receive topiramate 5, 15, or 25 mg/kg/day or placebo for 20 days with their current AEDs. Topiramate dosing was initiated at 3 mg/kg daily, then uptitrated every 3 days to the assigned dose or maximum tolerated dose. Reduction in seizure rate was assessed as the difference between baseline and endpoint 48-hour video-EEGs. The primary efficacy analysis compared each dose group with placebo, using a step-down procedure to control Type I error. Results: Of the 149 patients who were randomized, 19 (13%) discontinued treatment: 8 (22%) from the placebo group, 4 (11%) from the 5 mg/kg/day group, 4 (11%) from the 15 mg/kg/day group, and 3 (8%) from the 25 mg/kg/day group. The mean age of the patients was 12 months, 52% were boys, 61% were white. There was no significant difference (p = 0.97) in median percentage reduction from baseline in daily POS rate between topiramate 25 mg/kg (20.4%) and placebo (13.1%). Lower doses were not formally tested in accordance with the step-down testing procedure, but nominal p-values for these comparisons showed no treatment effect (p = 0.97 for the 15 mg/kg/day dose; p = 0.91 for the 5 mg/kg/day dose). Treatment-emergent fever, diarrhea, vomiting, anorexia, weight decrease, somnolence, and viral infection occurred more frequently (≥10% difference) with topiramate. Conclusions: Efficacy was not demonstrated using topiramate 5, 15, or 25 mg/kg/day as adjunctive treatment for refractory POS in infants 1 to 24 months old. No new safety concerns were noted.