Abstract
BackgroundEslicarbazepine acetate (ESL, Aptiom®) is a once-daily (QD) anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). It is extensively converted after oral administration to eslicarbazepine, and is believed to exert its effect through inhibition of voltage-gated sodium channels. The possible role of ESL as monotherapy to treat POS has not yet been established.MethodsThis study was an 18-week, multicenter, randomized double-blind trial of gradual conversion to ESL monotherapy in adults with POS not well controlled by 1–2 antiepileptic drugs (AEDs), using historical data as the control. The study comprised an 8-week baseline period, a 2-week titration period, a 6-week AED conversion period, a 10-week monotherapy period, and either a 1-week taper period or optional entry to an open-label extension study. The primary endpoint compared the Kaplan–Meier (KM)-estimated 112-day exit rate with a threshold value calculated from the historical controls.ResultsThere were 172 randomized patients; 154 (90%) entered the AED conversion period and 121 (70%) completed the study. The KM-estimated exit rates [confidence interval (CI)] were 15.6% [8.1–28.7%] for ESL 1200 mg, and 12.8% [7.5–21.5%] for ESL 1600 mg. The upper limits of the 95% CI KM-estimates were below the pre-specified threshold for historical control of 65.3%, indicating that ESL was efficacious in reducing seizure-related exits, compared with historical control. During the 18-week double-blind treatment period, median reductions in standardized seizure frequency occurred with ESL 1200 mg (36.1%) and ESL 1600 mg (47.5%). The responder rates (a 50% or greater reduction in seizure frequency from baseline) during the 18-week double-blind period and the monotherapy period, respectively, were 35.2% and 38.9% for ESL 1200 mg, and 46.0% and 46.0% for ESL 1600 mg. The overall adverse event profile was consistent with the known safety profile of ESL.ConclusionsThese findings indicate that ESL monotherapy (1200 and 1600 mg QD) was efficacious and well tolerated in this study.Trial registrationNCT01091662; EudraCT No. 2010-018684-42.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0305-5) contains supplementary material, which is available to authorized users.
Highlights
Eslicarbazepine acetate (ESL, Aptiom®) is a once-daily (QD) anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS)
Antiepileptic drug (AED) monotherapy is generally preferred to adjunctive therapy, due to the greater risk of adverse events (AEs) and adverse drug interactions with combination therapy [3]
AED monotherapy is valuable for certain types of patients, including women, the elderly, and those with co-morbid conditions, for whom AED toxicity and drug interactions may have additional consequences [4,5]
Summary
Eslicarbazepine acetate (ESL, Aptiom®) is a once-daily (QD) anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). It is extensively converted after oral administration to eslicarbazepine, and is believed to exert its effect through inhibition of voltage-gated sodium channels. Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment [2]. AED monotherapy is generally preferred to adjunctive therapy, due to the greater risk of adverse events (AEs) and adverse drug interactions with combination therapy [3]. There is an unmet clinical need for new AEDs that are both effective and well tolerated [4], for use as monotherapy in the treatment of patients with epilepsy. Eslicarbazepine has an apparent half-life of 13–20 hours in plasma [10] and 20–24 hours in cerebrospinal fluid [11], which supports once-daily (QD) dosing
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