Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy

dc.contributor.authorFrench, Jacqueline A.
dc.contributor.authorAbou-Khalil, Bassel W.
dc.contributor.authorLeroy, Robert F.
dc.contributor.authorYacubian, Elza Márcia Targas [UNIFESP]
dc.contributor.authorShin, Paul
dc.contributor.authorHall, Susan
dc.contributor.authorMansbach, Harry
dc.contributor.authorNohria, Virinder
dc.contributor.authorRESTORE 1 Study 301 Investigators
dc.contributor.institutionNYU
dc.contributor.institutionVanderbilt Univ
dc.contributor.institutionNeurol Clin Texas
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionValeant Pharmaceut Int
dc.contributor.institutionMercer Univ
dc.date.accessioned2018-06-18T11:15:20Z
dc.date.available2018-06-18T11:15:20Z
dc.date.issued2011-05-01
dc.description.abstractObjective: To evaluate the efficacy and safety of ezogabine (United States adopted name)/retigabine (international nonproprietary name) (EZG[RTG]) 1,200 mg/day as adjunctive treatment in adults with drug-resistant epilepsy with partial-onset seizures with or without secondary generalization.Methods: RESTORE 1 was a multicenter, randomized, double-blind, parallel-group trial. Following a prospective 8-week baseline phase, patients entered an 18-week double-blind treatment period (6-week forced dose titration to EZG[RTG] 1,200 mg/day in 3 equally divided doses or placebo, followed by a 12-week maintenance phase). Results were analyzed on an intent-to-treat basis for the entire 18-week period and for patients reaching the maintenance phase.Results: In 306 patients randomized, 305 received EZG(RTG) 1,200 mg/day (n = 153) or placebo (n = 152). Median percent reduction in total partial-seizure frequency was 44.3% vs 17.5% (p < 0.001) for EZG(RTG) and placebo, respectively, during the 18-week double-blind period; responder rates (>= 50% reduction in total partial-seizure frequency from baseline) were 44.4% vs 17.8% (p < 0.001). In 256 patients (EZG[RTG], 119; placebo, 137) entering the 12-week maintenance phase, median percent reduction in seizure frequency for EZG(RTG) vs placebo was 54.5% and 18.9% (p < 0.001), respectively; responder rates were 55.5% vs 22.6% (p < 0.001). The proportion of patients discontinuing due to treatment-emergent adverse events (TEAEs) was 26.8% (EZG[RTG]) vs 8.6% (placebo). Dizziness, somnolence, fatigue, confusion, dysarthria, urinary tract infection, ataxia, and blurred vision were the most common TEAEs reported by more patients treated with EZG(RTG) than placebo.Conclusions: This study demonstrates that EZG(RTG) is effective as add-on therapy for reducing seizure frequency in patients with drug-resistant partial-onset seizures.Classification of evidence: This study provides Class II evidence that EZG(RTG) 1,200 mg/day is effective as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. Neurology (R) 2011;76:1555-1563en
dc.description.affiliationNYU, Comprehens Epilepsy Ctr, Dept Neurol, New York, NY 10016 USA
dc.description.affiliationVanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN USA
dc.description.affiliationNeurol Clin Texas, Dallas, TX USA
dc.description.affiliationHosp Sao Paulo, Escola Paulista Med, UNIFESP, Dept Neurol & Neurosurg, Sao Paulo, Brazil
dc.description.affiliationValeant Pharmaceut Int, Aliso Viejo, CA USA
dc.description.affiliationValeant Pharmaceut Int, Res Triangle Pk, NC USA
dc.description.affiliationMercer Univ, Atlanta, GA USA
dc.description.affiliationUnifespHosp Sao Paulo, Escola Paulista Med, UNIFESP, Dept Neurol & Neurosurg, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipValeant Pharmaceuticals International, Aliso Viejo, CA, USA
dc.description.sponsorshipGlaxoSmithKline
dc.description.sponsorshipValeant Pharmaceuticals International
dc.description.sponsorshipUCB
dc.description.sponsorshipKyowa Hakko Kirin Pharma, Inc.
dc.description.sponsorshipEisai Inc.
dc.description.sponsorshipJohnson Johnson
dc.description.sponsorshipEpilepsy Therapy Development Project
dc.description.sponsorshipFACES
dc.description.sponsorshipSK Bio-Pharmaceuticals
dc.description.sponsorshipVertex Pharmaceuticals
dc.description.sponsorshipPfizer Inc.
dc.description.sponsorshipMerck Serono
dc.description.sponsorshipNIH
dc.description.sponsorshipEpilepsy Research Foundation
dc.description.sponsorshipCyberonics, Inc.
dc.description.sponsorshipSCHWARZ PHARMA
dc.description.sponsorshipOrtho-McNeil-Janssen Pharmaceuticals, Inc.
dc.description.sponsorshipJazz Pharmaceuticals
dc.description.sponsorshipOvation Pharmaceuticals
dc.description.sponsorshipEndo Pharmaceuticals
dc.description.sponsorshipBial Pharmaceuticals
dc.description.sponsorshipNeuro-Vista Corporation
dc.description.sponsorshipIcagen, Inc.
dc.description.sponsorshipSupernus Pharmaceuticals, Inc.
dc.description.sponsorshipIkano Therapeutics Inc.
dc.description.sponsorshipTaroPharma
dc.description.sponsorshipNeuroTherapeutics Pharma, Inc.
dc.description.sponsorshipSepracor Inc.
dc.description.sponsorshipNovartis
dc.description.sponsorshipMarinus Pharmaceuticals, Inc.
dc.description.sponsorshipOrtho McNeill
dc.description.sponsorshipAbbott
dc.description.sponsorshipSchwartz Biomedical
dc.description.sponsorshipLLC.
dc.description.sponsorshipLundbeck Inc. (Ovation)
dc.description.sponsorshipKing Pharmaceuticals
dc.description.sponsorshipSepacor Inc.
dc.format.extent1555-1563
dc.identifierhttp://dx.doi.org/10.​1212/​WNL.​0b013e3182194bd3
dc.identifier.citationNeurology. Philadelphia: Lippincott Williams & Wilkins, v. 76, n. 18, p. 1555-1563, 2011.
dc.identifier.doi10.​1212/​WNL.​0b013e3182194bd3
dc.identifier.issn0028-3878
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/45019
dc.identifier.wosWOS:000290150800007
dc.language.isoeng
dc.publisherLippincott Williams & Wilkins
dc.relation.ispartofNeurology
dc.rightsAcesso restrito
dc.titleRandomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsyen
dc.typeArtigo
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