PMID- 29030894 OWN - NLM STAT- MEDLINE DCOM- 20180620 LR - 20220316 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 23 IP - 12 DP - 2017 Dec TI - Pooled efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: Data from four double-blind placebo-controlled pivotal phase III clinical studies. PG - 961-972 LID - 10.1111/cns.12765 [doi] AB - PURPOSE: Pooled evaluation of the key efficacy and safety profile of eslicarbazepine acetate (ESL) added-on to stable antiepileptic therapy in adults with focal-onset seizures. METHODS: Data from 1703 patients enrolled in four phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2 week titration period, ESL was administered at 400 mg, 800 mg, and 1200 mg once-daily doses for 12 weeks (maintenance period). Pooled efficacy variable was standardized (/4 weeks) seizure frequency (SSF) analyzed over the maintenance period as reduction in absolute and relative SSF and proportion of responders (>/=50% reduction in SSF). Pooled safety was analyzed by means of adverse events and clinical laboratory assessments. RESULTS: SSF was significantly reduced with ESL 800 mg (P < 0.0001) and 1200 mg (P < 0.0001) compared to placebo. Median relative reduction in SSF was 33.4% for ESL 800 mg and 37.8% for 1200 mg (placebo: 17.6%), and responder rate was 33.8% and 43.1% (placebo: 22.2%). ESL was more efficacious than placebo regardless of gender, geographical region, epilepsy duration, age at time of diagnosis, seizure type, and type of concomitant antiepileptic drugs (AED). Incidence of adverse events (AEs) and AEs leading to discontinuation was dose dependent. Most common AEs (>10% patients) were dizziness, somnolence, and nausea. The incidence of treatment-emergent AEs (dizziness, somnolence, ataxia, vomiting, and nausea) was lower in patients who began taking ESL 400 mg (followed by 400 mg increments to 800 or 1200 mg) than in those who began taking ESL 600 mg or 800 mg. CONCLUSIONS: Once-daily ESL 800 mg and 1200 mg showed consistent results across all efficacy and safety endpoints, independent of study population characteristics and type of concomitant AEDs. Treatment initiated with ESL 400 mg followed by 400 mg increments to 800 or 1200 mg provides optimal balance of efficacy and tolerability. CI - (c) 2017 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd. FAU - Elger, Christian AU - Elger C AD - Department of Epileptology, University of Bonn, Bonn, Germany. FAU - Koepp, Mathias AU - Koepp M AD - Department of Clinical and Experimental Epilepsy, Institute of Neurology, London, UK. FAU - Trinka, Eugen AU - Trinka E AD - Department of Neurology, Christian Doppler Medical Centre and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria. FAU - Villanueva, Vicente AU - Villanueva V AD - Unidad Multidisciplinar de Epilepsia, Hospital Universitario y Politecnico La Fe, Valencia, Spain. FAU - Chaves, Joao AU - Chaves J AD - Servico de Neurologia, Hospital S. Antonio, Centro Hospitalar do Porto, Porto, Portugal. FAU - Ben-Menachen, Elinor AU - Ben-Menachen E AD - Department of Clinical Neuroscience and Physiology, Sahlgren Academy, Sahlgren University Hospital, Goteborg, Sweden. FAU - Kowacs, Pedro A AU - Kowacs PA AD - Curitiba Neurological Institute, Curitiba, Brazil. FAU - Gil-Nagel, Antonio AU - Gil-Nagel A AD - Epilepsy Program, Hospital Ruber Internacional, Madrid, Spain. FAU - Moreira, Joana AU - Moreira J AD - Department of Research and Development, BIAL - Portela & C feminine, S.A., S. Mamede do Coronado, Portugal. FAU - Gama, Helena AU - Gama H AD - Department of Research and Development, BIAL - Portela & C feminine, S.A., S. Mamede do Coronado, Portugal. FAU - Rocha, Jose-Francisco AU - Rocha JF AD - Department of Research and Development, BIAL - Portela & C feminine, S.A., S. Mamede do Coronado, Portugal. FAU - Soares-da-Silva, Patricio AU - Soares-da-Silva P AUID- ORCID: 0000-0002-2446-5078 AD - Department of Research and Development, BIAL - Portela & C feminine, S.A., S. Mamede do Coronado, Portugal. AD - Department of Biomedicine, Faculty of Medicine, Unit of Pharmacology and Therapeutics, University of Porto, Porto, Portugal. AD - MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal. LA - eng PT - Journal Article DEP - 20171013 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 RN - 0 (Anticonvulsants) RN - 0 (Dibenzazepines) RN - BEA68ZVB2K (eslicarbazepine acetate) SB - IM MH - Adolescent MH - Adult MH - Anticonvulsants/*therapeutic use MH - *Clinical Trials as Topic MH - Dibenzazepines/*therapeutic use MH - Dose-Response Relationship, Drug MH - *Double-Blind Method MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Randomized Controlled Trials as Topic MH - Seizures/*drug therapy MH - Treatment Outcome MH - Young Adult PMC - PMC5813188 OTO - NOTNLM OT - adjunctive therapy OT - adults OT - antiepileptic drugs OT - eslicarbazepine acetate OT - focal-onset seizures OT - refractory epilepsy COIS- C. Elger, M. Koepp, E. Trinka (reports speakers honoraria and consultancy fees from Eisai, Everpharma, Medtronics, Bial, Newbridge, UCB Pharma, Boehringer, and his institution received grants from Biogen Idec, Eisai, Red Bull, and Merck. He or his institution received grants from European Union, FWF Osterreichischer Fond zur Wissenschaftsforderung, Bundesministerium fur Wissenschaft und Forschung, and the Jubilaumsfond der Osterreichischen Nationalbank, outside the submitted work), V. Villanueva, J. Chaves, E. Ben-Menachen, P. A. Kowacs, and A. Gil-Nagel, have received research grants from BIAL, the sponsor of the studies. J. Moreira, H. Gama, J.F. Rocha, and P. Soares-da-Silva were employees of BIAL at the time of the studies. EDAT- 2017/10/17 06:00 MHDA- 2018/06/21 06:00 PMCR- 2017/10/13 CRDT- 2017/10/15 06:00 PHST- 2017/08/02 00:00 [received] PHST- 2017/09/14 00:00 [revised] PHST- 2017/09/18 00:00 [accepted] PHST- 2017/10/17 06:00 [pubmed] PHST- 2018/06/21 06:00 [medline] PHST- 2017/10/15 06:00 [entrez] PHST- 2017/10/13 00:00 [pmc-release] AID - CNS12765 [pii] AID - 10.1111/cns.12765 [doi] PST - ppublish SO - CNS Neurosci Ther. 2017 Dec;23(12):961-972. doi: 10.1111/cns.12765. Epub 2017 Oct 13.