Date: 2014-11-10
Type of information: Publication of results in a medical journal
phase:
Announcement: publication of results in the European Journal of Paediatric
Company: Eisai (Japan)
Product: Zonegran® (zonisamide)
Action
mechanism: Zonisamide is a second generation anti-epileptic drug (AED) with multiple mechanisms of action and a chemical structure which is unrelated to any other AEDs. The product is licensed in Europe as adjunctive therapy in the treatment of partial seizures (with or without generalisation) in adults with epilepsy. It has a broad spectrum of anti-epileptic modes of action and has no appreciable effects on steady-state plasma concentrations of other AEDs, such as phenytoin, carbamazepine and valproate. Zonisamide is licensed in Europe as monotherapy in the treatment of partial seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy. Zonisamide is also indicated in Europe as adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adults, adolescents and children aged six years and above. It has a broad spectrum of anti-epileptic modes of action and has no appreciable effects on steady-state plasma concentrations of other AEDs, such as phenytoin, carbamazepine and valproate.
Disease: paediatric partial onset seizures in children with partial epilepsy
Therapeutic area: CNS diseases - Neurological diseases
Country:
Trial details:
Latest
news: * On November 10, 2014, Eisai announced that safety data from 17 studies have been published in the European Journal of Paediatric. These newly published safety data from 17 studies support zonisamide\'s proven clinical efficacy in children aged six years and above. Zonisamide is indicated in Europe as adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adults, adolescents, and children aged six years and above. The pooled analysis includes 507 people aged ≤16 years involved in four randomised, double-blind studies and 13 uncontrolled, open-label trials. A total of 398 children received zonisamide and 109 received placebo. Most treatment emergent adverse events (TEAEs) were of mild or moderate intensity, the majority of which are already described in the safety profile for zonisamide. The most frequent treatment-related TEAEs were decreased appetite (15.6%), somnolence (12.1%), fatigue (9.3%), dizziness (6.0%), decreased weight (5.8%), irritability (5.8%) and headache (5.3%). The incidence of TEAEs that led to discontinuation was low 10.3%.
Study 312 was a double-blind, randomised, placebo-controlled, multi-centre study (n=207) to assess the efficacy and safety of adjunctive zonisamide in paediatric partial onset seizures (6-17 years old). In the study, children with partial epilepsy, receiving one or two anti-epileptic drugs, were randomised to receive either adjunctive zonisamide or placebo. Zonisamide was initiated at 1 mg/kg/day, titrated to a target dose of 8 mg/kg/day over eight weeks (one down-titration permitted) and maintained for 12 weeks. The primary efficacy end point of the study was the proportion of responders (defined as a ≥50% seizure frequency reduction from baseline) during the 12-week maintenance period.
The responder rates were found to be 50% for zonisamide vs. 31% for placebo (p = 0.0044). The overall incidence of treatment emergent adverse events (TEAEs) was similar for zonisamide (55.1%) vs. placebo (50.0%), with low rates of serious TEAEs in both arms of the study (3.7% zonisamide vs. 2.0% placebo) and TEAEs leading to withdrawal (0.9% vs. 3.0%).
Study 313 was an open-label extension study to assess the long-term efficacy and safety of adjunctive zonisamide in paediatric partial onset seizures (n=144, 6-18 years old), following Phase III study 312 (CATZ). Patients started with a double-blind transition period (2-11 weeks), during which patients on zonisamide continued at the same dose and those on placebo switched to zonisamide 1mg/kg/day, up-titrated to 8mg/kg/day to a maximum of 500mg/day. During the subsequent open label period (45-57 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 Behaviour 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.[1] mettre épilepsie en neurological diseases
