Zonegran (zonisamide) is well tolerated and efficacious when used as an adjunctive (add-on) treatment for partial epilepsy, with or without secondary generalization, in children aged between six and 17 years for at least one year, according to the results of a new study published today in Epilepsia.
The results of this study also showed that zonisamide was not associated with any unexpected safety issues or detrimental effects on children’s growth and development. Zonisamide is a second generation anti-epileptic drug (AED) with multiple mechanisms of action and a chemical structure unrelated to any other AEDs.
It is estimated that there are approximately 0.9 million children and adolescents living with active epilepsy in Europe. Epilepsy in children often presents major challenges such as developmental and behavioral problems, resulting in educational underachievement and a lack of self-esteem. These issues, which are frequently manifested in an attention deficit disorder, withdrawal, anxiety or depression, have a negative impact on both the child and their family.
“Unfortunately, more than a fourth of children with epilepsy remain refractory to treatment,” pointed out Professor Renzo Guerrini from the Children’s Hospital Anna Meyer-University of Florence, Italy. “There is still a need for additional treatment options. The results of this 1-year open-label extension of a randomized-controlled study of zonisamide are therefore particularly welcomed and zonisamide could be a valuable treatment option for children with partial epilepsy.”
The study was an open label extension of a Phase 3, double-blind, randomized, placebo-controlled, multicenter trial. It set out to assess the long-term safety/tolerability and explore the long-term maintenance of efficacy of adjunctive zonisamide in 144 children aged six to 18 years from 10 European countries. Patients started with a double-blind transition period (two to 11 weeks), during which patients on zonisamide continued at the same dose and those on placebo switched to zonisamide 1 mg/kg/day, up-titrated to 8 mg/kg/day to a maximum of 500 mg/day. During the subsequent open label period (45 to 57 weeks), zonisamide dosing was adjusted according to tolerability and response. Tolerability, efficacy, growth and development assessments were made throughout the study.
The results of the study showed a low incidence of serious treatment-emergent adverse events (TEAEs) (2.1%) and TEAEs leading to discontinuation from the study (2.8%). During the open-label period, 56.3% of patients were classified as responders to treatment and 11.1% achieved seizure freedom. Tanner staging (a scale of physical development in children, adolescents and adults) and skeletal development were as expected for the age range of children in the study. Changes were minimal for the Child Behavior Checklist (a widely used method of identifying problem behavior in children) and for school performance scores. Most of the children studied were ‘much improved’/’very much improved’ based on physician (73.8%) and parent/guardian (75.4%) global impressions of change. The results of the Controlled Oral Word Association Test (COWAT), an evaluation that measures the verbal fluency of an individual, and letter fluency scores, showed no evidence of impairment with zonisamide treatment.
Zonisamide was approved in Europe in 2005 as an adjunctive therapy in the treatment of partial seizures, with or without secondary generalization, in adults. In July 2012, the EC approved zonisamide as monotherapy in the treatment of partial seizures, with or without secondary generalization, in adults with newly diagnosed epilepsy. The use of the adjunctive zonisamide in the treatment of partial seizures (with or without secondary generalization) in children aged six years and above was approved by the European Commission in October 2013.
The zonisamide pediatric license was based on Study 312 (CATZ) published in Epilepsia in July 2013. These data from a double-blind, randomized, multicenter, placebo-controlled Phase 3 study, showed that significantly more patients aged six to 17 responded positively to treatment with zonisamide (50%) versus treatment with placebo (31%, p=0.0044). Safety and tolerability assessments showed that the overall incidence of TEAEs was similar for zonisamide versus placebo and that there were low rates of serious TEAEs in both groups.
Date: April 21, 2014
Source: Eisai Europe Ltd.