Abstracts

Levetiracetam (LEV, Keppra[reg]) is approved for the adjunctive treatment of partial onset seizures (PS) in adults ([gt] 16 years old) but its safety and efficacy in children with PS has not been systemically evaluated. Differences between pediatric and adult PS prevent simple extrapolation of adult data to children. This study was a multicenter, double blind, randomized, placebo controlled parallel group international (U.S.A., Canada) study of adjunctive LEV therapy in children 4 to 16 years old with PS uncontrolled on one or two standard antiepileptic drugs. Eligible patients having at least 8 PS with or without secondary generalization during an 8-week baseline period were randomized to either LEV (20 mg/kg/day) or placebo. During a 6-week titration period patients received up to 60 mg/kg/day followed by an 8-week evaluation period. At the end of the evaluation phase, patients could elect to continue in an open-label, long-term, follow-up trial or enter a 6-week withdrawal period. The treatment period was defined as the titration (6 weeks) and evaluation (8 weeks) periods combined, i.e., a total of 14 weeks. Adverse events, neurological and physical status, ECG, and laboratory safety tests were assessed during the treatment period. Two hundred eighty-two (282) patients were screened, 216 were randomized, 198 patients provided evaluable data, and 193 completed the treatment period. The primary efficacy analysis was based on the intent-to-treat population of 198 patients who provided evaluable data. The percentage reduction in PS frequency over placebo during the treatment period (the primary endpoint) was 26.8% for LEV (p = 0.0002). The percent of patients who had at least a 50% reduction of PS frequency per week was 44.6% (45/101 patients) for patients receiving LEV and 19.6% (19/97 patients) for patients receiving placebo (p = 0.0002). The percent of patients who had at least a 75% reduction of PS frequency per week was 19.8% (20/101 patients) with LEV and 5.1% (5/97 patients) with placebo (p [lt] 0.0001). Seven percent (7%, 7/101) LEV and one percent (1%, 1/97) placebo patients were seizure free during the treatment period. Preliminary assessments of the safety profile revealed a spectrum and frequency of treatment emergent adverse events similar to the safety profile in the current approved LEV labeling for adult use as adjunctive therapy in PS. The initial analysis of this randomized, double-blind, placebo-controlled trial indicates that in children (4 to 16 years of age) with treatment resistant partial onset seizures, LEV adjunctive therapy was associated with a significant reduction in partial onset seizure frequency with a spectrum of side effects similar to that seen in adults receiving adjunctive LEV therapy. (Supported by UCB S.A., Pharma Sector)