Press Briefing

Eslicarbazepine acetate appears to have no significant detrimental effect on neurocognitive function in children with epilepsy
Catherine Amey, Senior Medical Writer, Touch Medical Media, UK
Jon Shepheard, Neurology Account Director, Touch Medical Media, UK

22 June 2017, Lyon Convention Centre, Lyon, France

Eslicarbazepine acetate has no significant negative impact on attention, information processing and working memory in children, aged 6- to 16-years-old, with refractory focal onset epilepsy, according to phase II study 208 data presented at the 12th European Paediatric Neurology Society (EPNS) Congress in Lyon, France.1

Study 208 (ClinicalTrials.gov Identifier: NCT01527513) evaluated the effect of adjunctive eslicarbazepine acetate (n=83) versus placebo (n=40) on Power of Attention. Power of Attention was a composite measure, defined as the sum of the reaction time measures from the attentional tasks (simple reaction time [dominant hand only], choice reaction time and digit vigilance speed).

Study 208 is a phase II, randomised, double-blind, placebo-controlled study (Part I) followed by a one-year open-label, uncontrolled period (Part II). Part I consisted of a 4-week observational baseline period, a 12-week double-blind period (4-week up-titration and 8-week maintenance) and tapering-off periods (4–8 weeks of down-titration and follow-up). Patients received 10 mg/kg/day of eslicarbazepine acetate, which could be titrated up to 30 mg/kg/day according to clinical response (maximum 1200 mg once-daily).

In Part I of study 208, there were no significant Power of Attention differences between eslicarbazepine acetate and placebo, with a least squares (LS) mean difference of 33.2 milliseconds (95% confidence interval: -137.6, 204.0; p=0.700). There were also no statistically significant differences in children who received eslicarbazepine acetate versus placebo for secondary endpoints; these included continuity of attention, quality of working memory and speed of memory.

The overall incidences of treatment emergent adverse events (TEAEs) were similar between children who took eslicarbazepine acetate (45%) or placebo (48%).2The most frequently reported TEAEs with eslicarbazepine acetate treatment were headache, somnolence and vomiting.2

“Childhood and adolescence are critical times for learning and development,” explained Ann Connolly, Registered Advanced Nurse Practitioner Epilepsy (Childhood) at the National Children's Hospital, Adelaide and Meath Hospital, Dublin, Ireland. “These findings may indicate that eslicarbazepine acetate has no significant negative consequence on the neurocognitive capability of children. This is important as the treatment may help support normal learning and schooling, which will stand these children in good stead for the future.”

“A major treatment goal for neurologists managing childhood epilepsy is to achieve seizure freedom with minimal or no adverse effects, of which neurocognition is an important consideration. Few clinical trials have examined the cognitive effects of anti-epileptic drugs in childhood epilepsy so these new data are reassuring and support the use of eslicarbazepine acetate in these difficult-to-treat patients,” added Professor Stéphane Auvin, Professor of Epilepsy & Child Neurology at the Université Denis Diderot, member of the Paediatric Commission of ILAE and board member of the French Paediatric Neurology Society Paris, France.

It has been estimated that 10.5 million children and adolescents worldwide have active epilepsy.3 These children may have cognitive impairment or learning deficits.4 Epilepsy may therefore have a significant negative impact on children’s quality of life and academic achievement as well as on psychosocial outcomes in later life.5,6

Eslicarbazepine acetate is a voltage-gated sodium channel blocker that selectively targets the slow inactivated state of the sodium ion channel.7 This drug is indicated in Europe as an adjunctive therapy in adults, adolescents and children aged older than 6 years, with partial-onset seizures with or without secondary generalisation.8 Eslicarbazepine acetate is also indicated in Europe as a monotherapy in the treatment of partial-onset seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy.8

REFERENCES

1.Veggiotti P, Jóźwiak S, Rocha F, et al. Effect of eslicarbazepine acetate on neurocognitive functions in children with epilepsy. Presented at: 12th European Paediatric Neurology Society (EPNS) Congress, Lyon, France, 22 June 2017. Oral presentation #OC58.

2.Jóźwiak S, Veggiotii P, Rocha F, et al. Efficacy and tolerability of eslicarbazepine acetate in children with epilepsy: results from a phase II study. Presented at: 12th European Paediatric Neurology Society (EPNS) Congress, Lyon, France, 22 June 2017. Oral presentation #OC57.

3.Guerrini R. Epilepsy in children, Lancet, 2006;367:499–524.

4.Melbourne Chambers R, Morrison-Levy N, Chang S, et al. Cognition, academic achievement, and epilepsy in school-age children: a case-control study in a developing country, Epilepsy Behav, 2014;33:39–44.

5.Mitchell WG, Chavez JM, Lee H, Guzman BL. Academic underachievement in children with epilepsy, J Child Neurol, 1991;6:65–72.

6.Carpay HA, Vermeulen J, Stroink H, et al. Disability due to restrictions in childhood epilepsy, Dev Med Child Neurol, 1997;39:521–6.

7.Elger C, Bialer M, Cramer JA, et al. Eslicarbazepine acetate: a double-blind, add-on, placebo-controlled exploratory trial in adult patients with partial-onset seizures, Epilepsia, 2007;48:497–504.

8.Zebinix® (eslicarbazepine acetate) Summary of Product Characteristics. Available at: www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000988/WC500047225.pdf (accessed 4 July 2017).