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). Here we report 18-month efficacy, safety, and tolerability results from an ongoing open-label extension (OLE) study that enrolled patients from 2 double-blind (DB), placebo-controlled studies with dosages of 200 and 400 mg/day. Methods: Patients who completed 12 weeks of DB treatment were permitted to enter the OLE study. Carisbamate was initiated at a dosage of 400 mg/day and could be increased up to 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, reasons for discontinuation, adverse event reporting, and 6-month seizure freedom at the last visit were assessed. Results: Of the 1,127 patients randomized in the DB study, 1,008 entered the OLE study and provided efficacy data. At the time of the data cutoff, 138 patients were still ongoing but had not yet reached 18 months; of the remaining 870 patients, 466 (53.6%) completed at least 18 months of treatment. The majority of patients (57%) received a modal daily dosage of 400 mg/day or less, while 43% received >400 to 800 mg/day over the duration of 18 months. Through 18 months, the median percent reduction in POS frequency was 41.4%, and the responder rate was 41.8%. Forty-eight patients (4.8%) had achieved 6 months of seizure freedom. Carisbamate was well tolerated, and the rate of discontinuation from adverse events was low. Conclusions: In this open label extension study that included >1,000 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.