title: Efficacy and tolerability of levetiracetam as adjunctive therapy in Japanese patients with uncontrolled partial-onset seizures.
abstract: OBJECTIVE
  The aim of this study was to confirm the efficacy and safety of adjunctive levetiracetam in adult Japanese patients with uncontrolled partial-onset seizures.
  
  
  METHODS
  In a double-blind, placebo-controlled, confirmatory trial, eligible patients were randomized to receive levetiracetam 500, 1000, 2000, or 3000 mg/day or placebo for 16 weeks. The primary end-point was percentage reduction from baseline in seizure frequency/week over a 12-week evaluation period. Tolerability assessments were also conducted. Findings of this and a previous randomized, double-blind trial were compared.
  
  
  RESULTS
  Of 401 patients screened, 352 were randomized and 316 completed the study. Median percentage reduction in seizure frequency/week from baseline was 12.92%, 18.00%, 11.11% and 31.67% in the levetiracetam 500, 1000, 2000 and 3000-mg groups, respectively, compared with 12.50% in the placebo group. Unlike the previous trial, the primary efficacy analysis between the levetiracetam 1000 and 3000-mg and placebo groups did not reach statistical significance (P = 0.067). Exploratory analyses demonstrated that the difference in seizure reduction versus placebo was 14.93% (95% confidence interval, 1.98-27.64; P = 0.025) for the levetiracetam 3000-mg group. All levetiracetam doses were well tolerated. The main difference between the two trials was a high placebo response in the present trial.
  
  
  CONCLUSIONS
  The primary efficacy analysis did not reach statistical significance, a finding that could be attributed to an unexpectedly high placebo response. Nonetheless, exploratory analysis suggests that levetiracetam at 3000 mg/day may, at least marginally, be beneficial for patients with uncontrolled partial-onset seizures.
authors: NHO, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
authors: Yushi
authors: Y
authors: Inoue
authors: NHO, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.|Yaizu Hospital, Yaizu, Japan.
authors: Kazuichi
authors: K
authors: Yagi
authors: Department of Epilepsy, Movement Disorders and Physiology, School of Medicine, Kyoto University, Kyoto, Japan.
authors: Akio
authors: A
authors: Ikeda
authors: Toyosato Hospital, Tsukuba, Japan.
authors: Mutsuo
authors: M
authors: Sasagawa
authors: Akeno Medical Clinic, Ohita, Japan.
authors: Shigenobu
authors: S
authors: Ishida
authors: UCB Pharma, Tokyo, Japan.
authors: Atsushi
authors: A
authors: Suzuki
authors: UCB Pharma, Tokyo, Japan.
authors: Katsumi
authors: K
authors: Yoshida
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007564:Japan; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010889:Piracetam / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D015990:Placebo Effect; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam
keywords: adjunctive therapy; antiepileptic drug; efficacy; levetiracetam; partial-onset seizures