RESUMO
OBJECTIVE: To assess the efficacy, safety, and tolerability of adjunctive levetiracetam (LEV) in Chinese and Japanese adults with generalized tonic-clonic (GTC) seizures (N01159; NCT01228747). METHODS: This double-blind, randomized, placebo-controlled, multicenter phase III trial comprised: 4-week retrospective and 4-week prospective baseline, 12-week dose-adjustment, and 16-week evaluation periods. Chinese and Japanese patients ≥16 years old with idiopathic generalized, symptomatic generalized, or undetermined epilepsy with GTC seizures received a single-blind placebo during the prospective baseline, and then were randomized 1:1 to placebo or LEV 1,000 mg/day administered twice daily. Patients reporting GTC seizures up to week 8 had the LEV dosage increased to 3,000 mg/day. The primary efficacy variable was percent reduction from combined baseline in GTC seizures/week during the 28-week treatment period. RESULTS: Overall, 251 patients were randomized (208 from China; 43 from Japan); 141 (56.2%) completed the 28-week treatment period. Least-squares mean percent reduction from combined baseline in GTC seizures/week (treatment period) was placebo 12.6% versus LEV 68.8% (95% confidence interval, 44.0-68.2; p < 0.0001). GTC seizure frequency reduction occurred in both patients with idiopathic and symptomatic generalized epilepsy. The 50% responder rate (treatment period) was placebo 28.4% versus LEV 77.8%. Freedom from GTC seizures (evaluation period) was placebo 3.1% versus LEV 29.6%. Incidence of treatment-emergent adverse events (TEAEs; treatment period) was placebo 52.0% versus LEV 57.1%; most frequently nasopharyngitis, protein in urine, decreased platelet count, and pyrexia. Incidence of TEAEs leading to discontinuation was 4.8% versus 3.2%; incidence of serious TEAEs was 3.2% versus 0.8% for placebo and LEV, respectively; 3 patients taking placebo died versus none taking LEV. SIGNIFICANCE: In this trial, adjunctive LEV 1,000-3,000 mg/day was effective in reducing GTC seizure frequency in Chinese and Japanese patients ≥16 years old with GTC seizures. Seizure reduction occurred in both patients with idiopathic and symptomatic generalized epilepsy. LEV was well tolerated in this population.