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Efficacy and tolerability of levetiracetam as adjunctive therapy in J apanese patients with uncontrolled partial‐onset seizures
Author(s) -
Inoue Yushi,
Yagi Kazuichi,
Ikeda Akio,
Sasagawa Mutsuo,
Ishida Shigenobu,
Suzuki Atsushi,
Yoshida Katsumi
Publication year - 2015
Publication title -
psychiatry and clinical neurosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 74
eISSN - 1440-1819
pISSN - 1323-1316
DOI - 10.1111/pcn.12300
Subject(s) - levetiracetam , tolerability , placebo , medicine , randomized controlled trial , statistical significance , clinical trial , anesthesia , confidence interval , clinical endpoint , adverse effect , epilepsy , psychiatry , alternative medicine , pathology
Aims The aim of this study was to confirm the efficacy and safety of adjunctive levetiracetam in adult J apanese 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.