Objective: To compare the efficacy and safety of topiramate (sprinkle capsules or oral liquid) with placebo as adjunct to other antiepileptic drugs (AED) in reducing refractory partial onset seizure (POS) rates in infants.
Methods: This double-blind, international study was conducted from September 2005 to June 2007. Patients (N = 149) with clinical or EEG evidence of refractory POS were randomly assigned (1 : 1 : 1 : 1) to receive topiramate 5, 15, or 25 mg/kg per day or placebo for 20 days with their current AED. 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-h video EEG. The primary efficacy analysis compared each dose group with placebo, using a step-down procedure.
Results: 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, but nominal p values for these comparisons showed no treatment effect (p = 0.97 for the 15 mg/kg per day dose; p = 0.91 for the 5 mg/kg per day dose). Treatment-emergent fever, diarrhoea, vomiting, anorexia, weight decrease, somnolence and viral infection occurred more frequently (⩾10% difference) with topiramate.
Conclusion: Efficacy was not demonstrated using topiramate 5, 15, or 25 mg/kg per day as adjunctive treatment for refractory POS in infants 1 to 24 months old. No new safety concerns were noted.