Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial‐onset seizures: Results of a phase III, double‐blind, randomized, placebo‐controlled trial. (22nd December 2014)

• Record Type: Journal Article
• Authors: Sperling, Michael R.; Abou‐Khalil, Bassel; Harvey, Jay; Rogin, Joanne B.; Biraben, Arnaud; Galimberti, Carlo A.; Kowacs, Pedro A.; Hong, Seung Bong; Cheng, Hailong; Blum, David; Nunes, Teresa; Soares‐da‐Silva, Patrício; the 304 Study Team
• Is Part Of: Epilepsia. Volume 56:issue 2(2015:Feb.)
• Page Start: 244
• Page End: 253
• Publication Date: 2014-12-22
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.12894
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" id="epi12894-abs-0001"> <title>Summary</title> <sec id="epi12894-sec-0001" sec-type="section"> <title>Objective</title> <p>To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial‐onset seizures.</p> </sec> <sec id="epi12894-sec-0002" sec-type="section"> <title>Methods</title> <p>This randomized, placebo‐controlled, double‐blind, parallel‐group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial‐onset seizures despite treatment with 1–2 antiepileptic drugs (AEDs). After an 8‐week baseline period, patients were randomized to once‐daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1, 200 mg (n = 211). Following a 2‐week titration period, patients received ESL 800 or 1, 200 mg once‐daily for 12 weeks. Seizure data were captured and documented using event‐entry or daily entry diaries.</p> </sec> <sec id="epi12894-sec-0003" sec-type="section"> <title>Results</title> <p>Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1, 200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1, 200 mg (p < 0.001) both reduced SSF. There were no statistically significant interactions between treatment response and geographical region (p = 0.38) or diary version (p = 0.76). Responder rate (≥50% reduction in SSF) was significantly higher with ESL 1, 200 mg (42.6%, p < 0.001) but not ESL 800 mg (30.5%, p = 0.07) than placebo (23.1%). Incidence of treatment‐emergent adverse events (TEAEs) and TEAEs leading to discontinuation increased with ESL dose. The most common TEAEs were dizziness, somnolence, nausea, headache, and diplopia.</p> </sec> <sec id="epi12894-sec-0004" sec-type="section"> <title>Significance</title> <p>Adjunctive ESL 1, 200 mg once‐daily was more efficacious than placebo in adult patients with refractory partial‐onset seizures. The once‐daily 800 mg dose showed a marginal effect on SSF, but did not reach statistical significance. Both doses were well tolerated. Efficacy assessment was not affected by diary format used.</p> </sec> </abstract>