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Conversion to Monotherapy with Eslicarbazepine Acetate in Adults with Partial-Onset Seizures - Results of a North-American Study (P3.242)

2014; Lippincott Williams & Wilkins; Volume: 82; Issue: 10_supplement Linguagem: Inglês

10.1212/wnl.82.10_supplement.p3.242

1526-632X

Michael R. Sperling, Jay Harvey, David Blum, Todd Grinnell,

EEG and Brain-Computer Interfaces

OBJECTIVE Investigate the safety and efficacy of eslicarbazepine acetate (ESL) as monotherapy in North American patients with partial-onset seizures (POS). BACKGROUND ESL is a novel once-daily (QD) anticonvulsant, extensively converted after oral administration to eslicarbazepine, which blocks voltage-gated sodium- and calcium-channels. DESIGN/METHODS In this multicenter, double-blind, historical control study, adult patients treated with 1-2 antiepileptic drugs (AEDs) and 蠅4 POS in the 8 wks before screening and no 4-wk seizure-free period, were randomized 2:1 to ESL 1600/1200mg QD [2-wk titration; 6-wk monotherapy conversion (other AEDs withdrawn); 10-wk monotherapy]. Primary endpoint was the proportion of subjects meeting any of 5 exit criteria (i.e. worsening seizure control) at wk 16. Treatment was considered effective if the upper limit (UL) of the 95% CI for exit rate (Kaplan-Meier estimate) was lower than the lower limit of the pre-specified prediction interval (65.3%), based on historical controls. RESULTS Sixty-five subjects (mean age 38.7 yrs; 47.7% male) for ESL 1200mg and 128 (mean age 39.9 yrs; 47.7% male) for ESL 1600mg received double-blind treatment; 60 and 118 subjects entered the conversion phase, respectively. At baseline, maximum 2-day seizure rates (mean±SD) were 3.7±2.8 (ESL 1200mg) and 3.8±2.4 (ESL 1600mg); mean maximum 28-day seizure rates were 12.1±8.3 and 13.8±9.1, respectively. The difference between exit rates for ESL 1200mg (44.4% [95% CI 32.5-58.3]) and ESL 1600mg (28.7% [21.2-38.1]) was not significant (p=0.07). Exit rates were similar for subjects with or without carbamazepine use. ESL monotherapy was superior to historical controls (for both doses, UL of 95% CI <65.3%). Treatment-emergent adverse events (TEAEs) were: dizziness; headache; fatigue; somnolence; nausea; nasopharyngitis (蠅10% of subjects). 12.3% (ESL 1200mg) and 18.0% (ESL 1600mg) of subjects discontinued due to TEAEs. CONCLUSIONS During conversion to monotherapy in North American adults with POS, ESL was well-tolerated and was superior to historical controls. Study sponsored by Sunovion Pharmaceuticals Inc. Disclosure: Dr. Sperling has received personal compensation for activities with Acorda Therapeutics and electroCore. Dr. Sperling has received personal compensation in an editorial capacity for Epilepsia. Dr. Sperling9s institution has received research support from Sunovion, Eisai, Inc., UCB Pharma, Vertex, Neuronex, Lundbeck, SK Life Sciences, and Medtronic. Dr. Harvey has received personal compensation for activities with Sunovion Pharmaceuticals as a consultant, and UCB Pharma as a speaker. Dr. Harvey has received research support from UCB Pharma, Sunovion Pharmaceuticals, Lundbeck, Cyberonics, Vertex, GlaxoSmithKline Inc., SKLife, and Pfizer Inc. Dr. Blum has received personal compensation for activities with Sunovion Pharmaceuticals as an employee. Dr. Blum has received research support from Sunovion Pharmaceuticals. Dr. Grinnell has received personal compensation for activities with Sunovion Pharmaceuticals.