Abstracts

Rationale: Carisbamate, a novel neurotherapeutic compound, has previously demonstrated efficacy as adjunctive treatment of partial onset seizures (POS) across a broad dose range (300-1,600 mg/day). Three large double-blind (DB), placebo-controlled studies have been conducted. In this open-label extension (OLE) study of 1 of these studies, we assessed the long-term efficacy, safety, and tolerability of carisbamate over 18 months of treatment. Methods: After completion of a 16-week DB study that assessed fixed dosages of 100 to 1,600 mg/day carisbamate, patients could enroll in the OLE study with an initial target dosage of 400 to 800 mg/day. The dosage could be adjusted up to 1,600 mg/day, but was later capped at 800 mg/day. The long-term efficacy outcomes were the percent reduction of POS frequency relative to the pre-DB baseline period and the responder rate (proportion of patients with ≥50% reduction in POS frequency). Both measures were calculated using the intent-to-treat population with cumulative cases carried forward. In addition, retention at 18 months, adverse events and reasons for discontinuation, and 6-month seizure freedom at the last visit were assessed. Results: Of the 537 patients randomized in the DB study, 419 entered the OLE study and provided efficacy data. A total of 216 (51.6%) patients completed 18 months of treatment. The majority of patients (59.7%) received a modal daily dose of >400 to 800 mg/day, while 18.4% received 400 mg/day or less, and 21.9% received more than 800 mg/day over the duration of 18 months. Through 18 months, the median percent reduction of POS frequency was 42.7%, and the responder rate was 40.8%. Twelve patients (2.9%) had achieved 6 months seizure freedom. Carisbamate was well tolerated, with low cognitive and behavioral adverse event rates, and a low rate of discontinuation because of adverse events. Conclusions: In this open label extension study that included >400 patients treated for up to 18 months, 400 to 800 mg/day of carisbamate was effective as adjunctive treatment of POS, and demonstrated a high retention rate, and good tolerability. Support for this work was provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.