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Anti-epileptogenic Clinical Trial Designs in Epilepsy: Issues and Options

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Neurotherapeutics

Abstract

Although trials with anti-seizure drugs have not shown anti-epileptogenic or disease-modifying activity in humans, new compounds are on the horizon that may require novel trial designs. We briefly discuss the unique challenges and the available options to identify innovative clinical trial designs that differentiate novel anti-epileptogenic and disease-modifying compounds, preferably early in phase II, from current anti-seizure drugs. The most important challenges of clinical testing of agents for epilepsy prevention include having sufficient preclinical evidence for a suitable agent to proceed with a human trial of an anti-epileptogenic drug, and to demonstrate the feasibility of doing such a trial. Major challenges in trial design to assess agents for disease modification include the choice of suitable study parameters, the identification of a high-risk study population, the type of control, the time and duration of treatment, and a feasible follow-up period.

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Acknowledgments

Table 1 was modified from a table compiled and presented by D. Friedman at the 2010 NINDS Workshop ”Anti-epileptogenesis (AEG) and disease modification: alignment and validation of clinical targets and pre-clinical models”. We thank Dr. Dale Hesdorffer and Emma Benn, MPH for assistance in compiling epidemiological data and computing sample size and NNT estimates.

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Disclosures

D.S. received consultation and speaker fees and hospitality during the last 3 years from Abbott, Viropharma, and Novartis.

D. F. receives grant funding from the NIH (UL1 TR000038 from the National Center for the Advancement of Translational Science (NCATS), American Epilepsy Society, and faces. Dr. Friedman is an investigator at NYU on studies for UCB Inc/Schwarz Pharma and also receives salary support for work performed on behalf of The Epilepsy Study Consortium, a non-profit organization, for consulting and clinical trial-related activities. He receives no personal income for these activities. NYU receives a fixed amount from the Epilepsy Study Consortium towards his salary. Within the last year, The Epilepsy Study Consortium received payments for research services from Eisai Medical Research, GlaxoSmithKline, Impax, Johnson & Johnson, Mapp Pharmaceuticals, Novartis, Lundbeck, Pfizer, Sepracor, Sunovion, SK Life Science, Supernus Pharmaceuticals, UCB Inc/Schwarz Pharma, Upsher Smith, and Vertex.

DF is an investigator at NYU on studies for Eisai Medical Research, LCGH, Impax, Mapp Pharmaceuticals, Novartis, UCB Inc/Schwarz Pharma, Upsher Smith, and Vertex.

M.D. has no disclosures.

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Authors and Affiliations

  1. Epilepsy Research Group, Goethestrasse 5, 14163, Berlin, Germany

    Dieter Schmidt

  2. Comprehensive Epilepsy Center, NYU Langone Medical Center, New York, NY, 10016, USA

    Daniel Friedman

  3. Department of Neurology, HUP, 3400 Spruce Street, 3 West Gates, Philadelphia, PA, 19104, USA

    Marc A. Dichter

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  1. Dieter Schmidt
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Correspondence to Dieter Schmidt.

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Schmidt, D., Friedman, D. & Dichter, M.A. Anti-epileptogenic Clinical Trial Designs in Epilepsy: Issues and Options. Neurotherapeutics 11, 401–411 (2014). https://doi.org/10.1007/s13311-013-0252-z

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