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Articles
March 30, 2011

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

May 3, 2011 issue
76 (18) 1555-1563

Abstract

Objective:

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.

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Supplementary Material

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File (table_e-2.doc)

COINVESTIGATORS

Principal investigators who screened patients: Veronica Campanille, Hospital General de Agudos “Dr. Teodoro Alvarez,” Argentina; Silivia Sara Kochen, Hospital General de Agudos “Dr. J. M. Ramos Mejia,” Argentina; Stella Maris Valiensi, Hospital Italiano de Buenos Aires, Argentina; Roberto Oscar Giobellina, Fundacion Lennox, Argentina; Maria Jesus Frias, Hospital Privado Centro Medico de Cordoba, Argentina; Marielza Fernandez Veiga, Hosp. Univ. Prof Edgard Santos–UFBA, Salvador, Brazil; Maria Luiza G de Manreza, Hospital das Clinicas da Fac de Medicina de São Paulo, São Paulo, Brazil; Americo Ceiki Sakamoto, Hosp. das Clinicas de Ribeirao Preto-USP-CIREP, Ribeirao Preto, Brazil; Elza Marcia Yacubian, UNIFESP–Escola Paulista de Medicina–Hospital São Paulo, São Paulo, Brazil; Patrick Cossette, CHUM–Hôpital Notre-Dame, Montreal, QC, Canada; Abayomi Ogunyemi, Health Sciences Centre, St. John's, NF, Canada; William Murphy, Foothills Medical Centre, Calgary, AB, Canada; Neelan Pillay, Foothills Medical Centre, Calgary, AB, Canada; Elout Starreveld, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada; Samuel Wiebe, Foothills Medical Centre, Calgary, AB, Canada; Maria Marcela Josefina Perez, Hospital de Psiquiatria San Fernando, IMSS, Mexico; Albino Contreras Milian, Hospital y Clinica OCA/MIRC, Monterrey, Mexico; Lilia Nunez-Orozco; Centro Medico 20 de Noviembre, Mexico; Jose Luis Ruiz-Sandoval, Antiguo Hospital Civil de Guadalajara, Guadajalara, Mexico; Gloria Llamosa-Garcia Velazquez, CIF BIOTEC, Medica Sur, Mexico; Catherine Boll, Instituto Nacional de Neurologia y Neurocirugia, Mexico; Bassel Abou-Khalil, Vanderbilt University Medical Center, Nashville, TN; Imran Ali, Medical University of Ohio at Toledo, Toledo, OH; Robert Armstrong, Asheville Neurology Specialists, Asheville, NC; Paul Ash, Oregon Neurology, PC, Tualatin, OR; Ronald Aung-Din, Lovelace Scientific Resources, Sarasota, FL; Victor Biton, Clinical Trials Inc., Little Rock, AR; David Burdette, Henry Ford Hospital, Detroit, MI; Steve S. Chung, Barrow Neurological Institute, Phoenix, AZ; Jeffrey Cohen, Beth Israel Medical Center, New York, NY; Scott Cooper, BBCI Clinical Trials, Cumming, GA; John DeCerce, University of Florida–Shands Jacksonville Neuroscience Institute, Jacksonville, FL; Marc Dichter, Hospital of the University of Pennsylvania, Philadelphia, PA; Roy Elterman, Medical City Dallas Hospital, Dallas, TX; Toufic Fakhoury, University of Kentucky, Lexington, KY; Raymond Faught, University of Alabama at Birmingham, Birmingham, AL; Nathan Fountain, University of Virginia Health System, Charlottesville, VA; Jacqueline A. French, Hospital of the University of Pennsylvania, Philadelphia, PA; Richard Hull, North Alabama Neuroscience Research Associates, Huntsville, AL; Avinash Khatter, Discovery Alliance Inc., Phoenix, AZ; Pavel Klein, Bethesda, MD; David Ko, University of Southern California, Neurology, Los Angeles, CA; Robert Leroy, Neurological Clinic-Texas, Dallas, TX; Paul McCabe, Milton S. Hershey Medical Center, Hershey, PA; David B. Moore, McFarland Clinic, Ames, IA; Patricia Penovich, MN Epilepsy Group, P.A., St. Paul, MN; Richard Ramsay, University of Miami, Miami, FL; William Rosenfeld, The Comprehensive Epilepsy Care Ctr for Children & Adults, Chesterfield, MO; Pradumna Singh, Meharry Medical College, Nashville, TN; Jeremy Slater, University of Texas Health Science Center at Houston, Houston, TX; Stephen Spillers, Delta Waves, Colorado Springs, CO; Mark Spitz Jr., University of Colorado Health Science Center, Denver, CO; Evelyn Tecoma, UCSD Medical Center, La Jolla, CA; Alexandre Todorov, Neurology Clinic, Northport, AL; Alan Towne, Virginia Commonwealth University, Richmond, VA; Roi Wallis, West Los Angeles VA Healthcare Center, Los Angeles, CA.

REFERENCES

1.
Elger CE, Schmidt D. Modern management of epilepsy: a practical approach. Epilepsy Behav 2008;12:501–539.
2.
Yonekawa WD, Kapetanovic IM, Kupferberg HJ. The effects of anticonvulsant agents on 4-aminopyridine induced epileptiform activity in rat hippocampus in vitro. Epilepsy Res 1995;20:137–150.
3.
Rundfeldt C. The new anticonvulsant retigabine (D-23129) acts as an opener of K+ channels in neuronal cells. Eur J Pharmacol 1997;336:243–249.
4.
Armand V, Rundfeldt C, Heinemann U. Effects of retigabine (D-23129) on different patterns of epileptiform activity induced by 4-aminopyridine in rat entorhinal cortex hippocampal slices: Naunyn-Schmiedebergs Arch Pharmacol 1999;359:33–39.
5.
Dost R, Rundfeldt C. The anticonvulsant retigabine potently suppresses epileptiform discharges in the low Ca++ and low Mg++ model in the hippocampal slice preparation. Epilepsy Res 2000;38:53–66.
6.
Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK. Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol 2000;58:591–600.
7.
Tatulian L, Delmas P, Abogadie FC, Brown DA. Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anticonvulsant drug retigabine. J Neurosci 2001;21:5535–5545.
8.
Wuttke TV, Seebohm G, Bail S, Maljevic S, Lerche H. The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol 2005;67:1009–1017.
9.
Dailey JW, Jae Hoo C, Ko KH, Leah EAC, Phillip CJ. Anticonvulsant properties of D-20443 in genetically epilepsy-prone rats: prediction of clinical response. Neurosci Lett 1995;195:77–80.
10.
Tober C, Rostock A, Rundfeldt C, Bartsch R. D-23129: a potent anticonvulsant in the amygdala kindling model of complex partial seizures. Eur J Pharmacol 1996;303:163–169.
11.
Rostock A, Tober C, Rundfeldt C, et al. D-23129: a new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures. Epilepsy Res 1996;23:211–223.
12.
Srivastava AK, White HS. Retigabine decreases behavioral and electrographic seizures in the lamotrigine-resistant amygdale-kindled rat model of pharmacoresistance. Epilepsia 2005;46(suppl 8):217–218.
13.
Smith MD, Adams AC, Saunders GW, White HS, Wilcox KS. Phenytoin- and carbamazepine-resistant spontaneous bursting in rat entorhinal cortex is blocked by retigabine in vitro. Epilepsy Res 2007;74:97–106.
14.
Ferron GM, Paul J, Fruncillo R, et al. Multiple-dose, linear, dose-proportional pharmacokinetics of retigabine in healthy volunteers. J Clin Pharmacol 2002;42:175–182.
15.
Borlak J, Gasparic A, Locher M, Schupke H, Hermann R. N-Glucuronidation of the antiepileptic drug retigabine: results from studies with human volunteers, heterologously expressed human UGTs, human liver, kidney, and liver microsomal membranes of Crigler Najjar type II. Metabolism 2006;55:711–721.
16.
Hempel R, Schupke H, McNeilly PJ, et al. Metabolism of Retigabine (D-23129), a novel anticonvulsant. Drug Metab Dispos 1999;27:613–622.
17.
Porter RJ, Partiot A, Sachdeo R, Nohria V, Alves WM. Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures. Neurology 2007;68:1197–1204.
18.
Brodie MJ, Lerche H, Gil-Nagel A, et al., RESTORE 2 Study Group. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology 2010;75:1817–1824.
19.
Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010;51:1069–1077.
20.
Barry MJ, Fowler FJ, O'Leary MP, et al. The American Urological Association symptom index for benign prostatic hyperplasia: The Measurement Committee of the American Urological Association. J Urol 1992;148:1549–1557.
21.
Bandolier. Number needed to treat (NNT). Available at: http://www.medicine.ox.ac.uk/bandolier/band59/NNT1.html. Accessed August 25, 2010.
22.
Gazzolla DM, Balcer LJ, French JA. Seizure-free outcome in randomized add-on trials of the new antiepileptic drugs. Epilepsia 2007;48:1303–1307.
23.
Leppik I, Morrell M, Godfroid P, Arrigo C. Seizure-free days observed in randomized placebo-controlled add-on trials with levetiracetam in partial epilepsy. Epilepsia 2003;44:1350–1352.
24.
Markowitz MA, Mauskopf JA, Halpern MT. Cost-effectiveness model of adjunctive lamotrigine for the treatment of epilepsy. Neurology 1998;51:1026–1033.
25.
Vera-Llonch M, Brandenburg NA, Oster G. Cost-effectiveness of add-on therapy with pregabalin in patients with refractory partial epilepsy. Epilepsia 2008;49:431–437.
26.
French JA, Kugler AR, Robbins JL, Knapp LE, Garofalo EA. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology 2003;60:1631–1637.
27.
Elger CE, Brodie MJ, Anhut H, Lee CM, Barrett JA. Pregabalin add-on treatment in patients with partial seizures: a novel evaluation of flexible-dose and fixed-dose treatment in a double-blind, placebo-controlled study. Epilepsia 2005;46:1926–1936.
28.
Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia 2007;48:1308–1317.
29.
Elger C, Halász P, Maia J, Almeida L, Soares-da-Silva P, BIA-2093–301 Investigators Study Group. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures: a randomized, double-blind, placebo-controlled, parallel-group phase III study. Epilepsia 2009;50:454–463.
30.
Zaccara G, Gangemi PF, Cincotta M. Central nervous system adverse effects of new antiepileptic drugs. A meta-analysis of placebo-controlled studies. Seizure 2008;17:405–421.
31.
Streng T, Christoph T, Andersson K-E. Urodynamic effects of the K+ channel (KCNQ) opener retigabine in freely moving, conscious rats. J Urol 2004;172:2054–2058.
32.
Wickenden AD, Zou A, Wagoner PK, Jegla T. Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells. Br J Pharmacol 2001;132:381–384.
33.
Schenzer A, Friedrich T, Pusch M, et al. Molecular determinants of KCNQ (Kv7) K+ channel sensitivity to the anticonvulsant retigabine. J Neurosci 2005;25:5051–5060.

Information & Authors

Information

Published In

Neurology®
Volume 76Number 18May 3, 2011
Pages: 1555-1563
PubMed: 21451152

Publication History

Received: September 23, 2010
Accepted: January 19, 2011
Published online: March 30, 2011
Published in print: May 3, 2011

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Disclosure

Dr. French has served on scientific advisory boards for UCB, Johnson & Johnson, Eisai Inc., Novartis, Valeant Pharmaceuticals International, Icagen, Inc., Ikano Therapeutics Inc., Sepracor Inc., and Marinus Pharmaceuticals, Inc.; has received funding for travel from UCB, Kyowa Hakko Kirin Pharma, Inc., Eisai Inc., Johnson & Johnson, Valeant Pharmaceuticals International, and GlaxoSmithKline; serves as an Associate Editor of Epilepsy Currents and Supplement Editor for Epileptic Disorders; estimates that 30% of her time is spent in outpatient epilepsy practice; receives research support from the Epilepsy Therapy Development Project, FACES, Johnson & Johnson, Eisai Inc., UCB, SK Bio-Pharmaceuticals, Valeant Pharmaceuticals International, Vertex Pharmaceuticals, Pfizer Inc, Merck Serono, the NIH, and the Epilepsy Research Foundation; and serves as President of the Epilepsy Study Consortium, which receives money from multiple pharmaceutical companies. A fixed 20% of her NYU salary is paid by the study consortium, some of which may come from consulting fees from GlaxoSmithKline, Pfizer Inc, UCB, Johnson & Johnson, Cyberonics, Inc., SCHWARZ PHARMA, Ortho-McNeil-Janssen Pharmaceuticals, Inc., Eisai Inc., Jazz Pharmaceuticals, Ovation Pharmaceuticals, Endo Pharmaceuticals, Bial Pharmaceuticals, NeuroVista Corporation, Valeant Pharmaceuticals International, Icagen, Inc., Supernus Pharmaceuticals, Inc., Ikano Therapeutics Inc., SK Bio-Pharmaceuticals, TaroPharma, NeuroTherapeutics Pharma, Inc., Sepracor Inc., and Novartis. Dr. Abou-Khalil serves as a consultant for UCB and receives research support from Valeant Pharmaceuticals International, UCB, SCHWARZ PHARMA, Marinus Pharmaceuticals, Inc., Ortho McNeill, GlaxoSmithKline, Pfizer Inc, and Abbott. Dr. Leroy serves on speakers' bureaus for and has received speaker honoraria from GlaxoSmithKline, UCB, and Cyberonics, Inc.; and receives research support from UCB, Schwartz Biomedical, LLC., Lundbeck Inc. (Ovation), King Pharmaceuticals, Pfizer Inc, GlaxoSmithKline, Valeant Pharmaceuticals International, Novartis, Eisai Inc., Sepacor Inc., Johnson & Johnson, and Bial. Dr. Yacubian serves on scientific advisory boards for Novartis, Abbott, and Johnson & Johnson; and has received funding for travel and speaker honoraria from Abbott and Novartis. P. Shin was an employee of Valeant Pharmaceuticals North America at the time of the study. Dr. Hall is an employee of and holds stock and stock options in Valeant Pharmaceuticals North America. Dr. Mansbach was an employee of Valeant Pharmaceuticals North America at the time of the study; has served as a consultant for and received funding for travel from GlaxoSmithKline; and holds stock in Valeant Pharmaceuticals International. Dr. Nohria was a paid consultant to Valeant Pharmaceuticals North America during the course of the study and the preparation of this manuscript; serves on a scientific advisory board for Antisense Pharma GmbH; serves/has served as a consultant for UCB/SCHWARZ PHARMA, Archimedes Pharma, Shire plc, Marinus Pharmaceuticals, Inc., Upsher-Smith Laboratories, and Antisense Pharma; and is a non-executive director of Allergy Therapeutics plc, in which he holds stock, and an executive officer of Alaven Pharmaceutical LLC.

Authors

Affiliations & Disclosures

J.A. French, MD
From the Department of Neurology (J.A.F.), New York University Comprehensive Epilepsy Center, New York; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; Neurological Clinic of Texas (R.F.L.), Dallas, TX; Department of Neurology and Neurosurgery (E.M.T.Y.), UNIFESP–Escola Paulista de Medicina–Hospital São Paulo, São Paulo, Brazil; Valeant Pharmaceuticals International (P.S., H.M.), Aliso Viejo, CA; Valeant Pharmaceuticals International (S.H.), Research Triangle Park, NC; and Mercer University (V.N.), Atlanta, GA. H.M. is currently affiliated with Medivation Inc., San Francisco, CA. P.S. is currently affiliated with Prometheus Therapeutics & Diagnostics, San Diego, CA.
B.W. Abou-Khalil, MD
From the Department of Neurology (J.A.F.), New York University Comprehensive Epilepsy Center, New York; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; Neurological Clinic of Texas (R.F.L.), Dallas, TX; Department of Neurology and Neurosurgery (E.M.T.Y.), UNIFESP–Escola Paulista de Medicina–Hospital São Paulo, São Paulo, Brazil; Valeant Pharmaceuticals International (P.S., H.M.), Aliso Viejo, CA; Valeant Pharmaceuticals International (S.H.), Research Triangle Park, NC; and Mercer University (V.N.), Atlanta, GA. H.M. is currently affiliated with Medivation Inc., San Francisco, CA. P.S. is currently affiliated with Prometheus Therapeutics & Diagnostics, San Diego, CA.
R.F. Leroy, MD
From the Department of Neurology (J.A.F.), New York University Comprehensive Epilepsy Center, New York; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; Neurological Clinic of Texas (R.F.L.), Dallas, TX; Department of Neurology and Neurosurgery (E.M.T.Y.), UNIFESP–Escola Paulista de Medicina–Hospital São Paulo, São Paulo, Brazil; Valeant Pharmaceuticals International (P.S., H.M.), Aliso Viejo, CA; Valeant Pharmaceuticals International (S.H.), Research Triangle Park, NC; and Mercer University (V.N.), Atlanta, GA. H.M. is currently affiliated with Medivation Inc., San Francisco, CA. P.S. is currently affiliated with Prometheus Therapeutics & Diagnostics, San Diego, CA.
E.M.T. Yacubian, MD
From the Department of Neurology (J.A.F.), New York University Comprehensive Epilepsy Center, New York; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; Neurological Clinic of Texas (R.F.L.), Dallas, TX; Department of Neurology and Neurosurgery (E.M.T.Y.), UNIFESP–Escola Paulista de Medicina–Hospital São Paulo, São Paulo, Brazil; Valeant Pharmaceuticals International (P.S., H.M.), Aliso Viejo, CA; Valeant Pharmaceuticals International (S.H.), Research Triangle Park, NC; and Mercer University (V.N.), Atlanta, GA. H.M. is currently affiliated with Medivation Inc., San Francisco, CA. P.S. is currently affiliated with Prometheus Therapeutics & Diagnostics, San Diego, CA.
P. Shin, MS
From the Department of Neurology (J.A.F.), New York University Comprehensive Epilepsy Center, New York; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; Neurological Clinic of Texas (R.F.L.), Dallas, TX; Department of Neurology and Neurosurgery (E.M.T.Y.), UNIFESP–Escola Paulista de Medicina–Hospital São Paulo, São Paulo, Brazil; Valeant Pharmaceuticals International (P.S., H.M.), Aliso Viejo, CA; Valeant Pharmaceuticals International (S.H.), Research Triangle Park, NC; and Mercer University (V.N.), Atlanta, GA. H.M. is currently affiliated with Medivation Inc., San Francisco, CA. P.S. is currently affiliated with Prometheus Therapeutics & Diagnostics, San Diego, CA.
S. Hall, PhD
From the Department of Neurology (J.A.F.), New York University Comprehensive Epilepsy Center, New York; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; Neurological Clinic of Texas (R.F.L.), Dallas, TX; Department of Neurology and Neurosurgery (E.M.T.Y.), UNIFESP–Escola Paulista de Medicina–Hospital São Paulo, São Paulo, Brazil; Valeant Pharmaceuticals International (P.S., H.M.), Aliso Viejo, CA; Valeant Pharmaceuticals International (S.H.), Research Triangle Park, NC; and Mercer University (V.N.), Atlanta, GA. H.M. is currently affiliated with Medivation Inc., San Francisco, CA. P.S. is currently affiliated with Prometheus Therapeutics & Diagnostics, San Diego, CA.
H. Mansbach, MD
From the Department of Neurology (J.A.F.), New York University Comprehensive Epilepsy Center, New York; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; Neurological Clinic of Texas (R.F.L.), Dallas, TX; Department of Neurology and Neurosurgery (E.M.T.Y.), UNIFESP–Escola Paulista de Medicina–Hospital São Paulo, São Paulo, Brazil; Valeant Pharmaceuticals International (P.S., H.M.), Aliso Viejo, CA; Valeant Pharmaceuticals International (S.H.), Research Triangle Park, NC; and Mercer University (V.N.), Atlanta, GA. H.M. is currently affiliated with Medivation Inc., San Francisco, CA. P.S. is currently affiliated with Prometheus Therapeutics & Diagnostics, San Diego, CA.
V. Nohria, MD On behalf of the RESTORE 1/Study 301 Investigators
From the Department of Neurology (J.A.F.), New York University Comprehensive Epilepsy Center, New York; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; Neurological Clinic of Texas (R.F.L.), Dallas, TX; Department of Neurology and Neurosurgery (E.M.T.Y.), UNIFESP–Escola Paulista de Medicina–Hospital São Paulo, São Paulo, Brazil; Valeant Pharmaceuticals International (P.S., H.M.), Aliso Viejo, CA; Valeant Pharmaceuticals International (S.H.), Research Triangle Park, NC; and Mercer University (V.N.), Atlanta, GA. H.M. is currently affiliated with Medivation Inc., San Francisco, CA. P.S. is currently affiliated with Prometheus Therapeutics & Diagnostics, San Diego, CA.

Notes

Study funding: Supported by Valeant Pharmaceuticals International, Aliso Viejo, CA, USA. Research funding for design and conduct of this study, collection, management, analysis, and interpretation of the data were sponsored by Valeant Pharmaceuticals. Preparation of the manuscript was sponsored by GlaxoSmithKline and Valeant Pharmaceuticals International.
Address correspondence and reprint requests to Dr. Jacqueline A. French, NYU Comprehensive Epilepsy Center, 223 East 34th Street, New York, NY 10016 [email protected]

Author Contributions

All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. Editorial support in the form of minuting author meetings, editing and formatting the manuscript, collating author comments, assembling tables and figures, and coordinating submission requirements was provided by David Gibson, PhD, CMPP, and Ing Haviland of Caudex Medical, New York, NY (supported by GlaxoSmithKline and Valeant Pharmaceuticals International). All authors (academic investigators [J.A.F., B.W.A.-K., R.F.L., E.M.Y., and V.N.] and employees of the sponsor [P.S., S.H., and H.M.]) had full access to and interpreted the data, and were responsible for the decision to publish the report. The sponsor did not place any restrictions on the academic authors about the statements made in the final report. J.A. French was a study investigator, contributed to the conception, design, and conduct of the study, contributed to data analysis and interpretation, and oversaw the development of the manuscript. She takes responsibility for the data, accuracy of the data analysis, and the conduct of the research. B.W. Abou-Khalil, R.F. Leroy, and E.M.T. Yacubian were study investigators and contributed to interpretation of the data and revision of the manuscript. P. Shin contributed to the conception, design, oversight, and conduct of the study, to the data analysis and interpretation, and to the revision of the manuscript. S. Hall contributed to the data analyses and interpretations and contributed to the revision of the manuscript. H. Mansbach contributed to the conduct of the study, data analysis and interpretation, and to the revision of the manuscript. V. Nohria contributed to the conception, design, and conduct of the study, and to data analysis and interpretation. He contributed to the first and subsequent drafts of the manuscript.

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