Abstracts

Rationale: Clobazam is approved in the US for treatment of Lennox-Gastaut Syndrome. The purpose of this study is to evaluate efficacy and safety of clobazam add-on treatment in adults with refractory focal epilepsy. Methods: This is a single center open label prospective study. After a prospective baseline of 26 weeks clobazam was added, administered orally in b.i.d. schedule. In patients in whom seizure diaries had been kept prospectively prior to study screening visit, the retrospective baseline was accepted. Patients were titrated up to seizure freedom, side effects or 40 mg/day, whichever came first. Titration rate was not forced. Starting dose was 10 mg/day, followed by default weekly 10 mg/day dose increments. Maintenance treatment lasted 12 weeks, for targeted whole treatment period of 16 weeks. At the end of 16 weeks' treatment, patients could enter study extension for further 36 weeks, for 1year total treatment duration. Primary efficacy outcome measure was seizure count/28 days. Primary efficacy outcomes were seizure freedom and ?-75% seizure reduction for the whole treatment period. Secondary efficacy outcomes included seizure freedom and ?-75% seizure reduction for the maintenance treatment period and mean % seizure reduction, ?-90% and ?-50% seizure reduction during whole treatment-, maintenance and 12 month extension treatment periods. Safety outcome measures were treatment emergent adverse events, treatment discontinuation due to TEAEs and serious adverse events. Intent-to-treat analysis was used. Results: The study is ongoing. 20 patients have enrolled to-date (12M, 8F, mean age 42 years, mean epilepsy duration 28 years, mean number of prior AEDS 7, mean number of concomitant AEDs 2). 13 patients have completed 16 weeks' treatment to-date. 3 patients (23%) stopped treatment early, 1 for social reasons, 2 for lack of efficacy. 5/13 (39%) patients did not reach the target dose of 40 mg/day because of TEAEs. 1/13 (8%) patient exceeded that dose (50 mg/day) to maximize efficacy. 2/13 (15%) patients were seizure free during the whole treatment period, 3 (23%) during maintenance treatment. ?-90-, ?-75%- and ?-50% seizure frequency reduction for the whole treatment period occurred in 4/13 (31%), 6/13 (46%) and 8/13 (62%) patients. Mean seizure frequency/28 days decreased from 14.5 at baseline by 62% and 63% to 5.5 and 5.4 during whole treatment- and maintenance treatment periods (both p=0.01, Wilcoxon test). TEAEs occurred in 11/13 (85%) patients, resulting in treatment discontinuation in 1/13 (8%) patients and in dose-reduction in 9/13 (69%) patients. Most TEAEs were mild to moderate in severity and resolved with dose reduction. Commonest TEAEs were somnolence (54%), dizziness/ataxia (46%), fatigue (31%), irritability/anger (15%), blurred vision (15%) and weight gain (54%). Conclusions: Adjunctive clobazam treatment may be effective in adults with refractory focal epilepsy. A significant proportion of previously refractory patients may achieve 75-100% seizure reduction. Side effects are common, but abate with flexible dose adjustment in most patients. Funding: Lundbeck