Efficacy of levetiracetam: a review of three pivotal clinical trials.

Levetiracetam is a novel antiepileptic drug (AED) with favorable pharmacologic characteristics and demonstrated activity in improving seizure control. Three multicenter double-blind, placebo-controlled studies were conducted in 904 patients with refractory partial-onset seizures. Patients were required to have a minimum of two or four seizures per week (depending on the study) and were maintained on a stable regimen of one or two AEDs at baseline that was continued during the study period. Patients ranged in age from 14 to 70 years, with a mean age of approximately 37 years. After an 8- to 12-week baseline period, patients were randomized and had doses titrated upward every 2 weeks over a period of 4 weeks to a target dose of 1,000, 2,000, or 3,000 mg/day of levetiracetam or placebo. Treatment was continued for a 12- to 14-week evaluation phase followed by an optional open-label treatment phase. The treatment period consisted of the dose titration period combined with the evaluation period. The median percentage reduction in seizure frequency (over placebo) was calculated for each of the levetiracetam treatment groups over the entire treatment period. For all levetiracetam dose groups, in all studies, reduction in seizure frequency over placebo was statistically significant (p < or = 0.001). Median percentage reductions were 26.1% and 17.1% in the 1,000-mg/day groups (study 1 and study 2, respectively), 21.4% in the 2,000-mg/day group (study 2), and 30.1% and 23.0% in the 3,000-mg/day groups (study 1 and study 3, respectively). The percentage of patients achieving a > or = 50% reduction from baseline in seizure frequency compared with the treatment period was 37.1% and 20.8% in the 1,000-mg/day groups (study 1 and study 2, respectively), 35.2% in the 2,000-mg/day group (study 2), and 39.6% and 39.4% in the 3,000-mg/day groups (study 1 and study 3, respectively). These responder rates were significantly higher than those for placebo (p < 0.001 for all comparisons). Levetiracetam was generally well tolerated in all studies. Results from these three pivotal studies demonstrate that levetiracetam, as adjunctive therapy, is a safe and effective treatment for refractory partial-onset seizures in adults.