Full-Length Original Research
Adjunctive zonisamide therapy in the long-term treatment of children with partial epilepsy: Results of an open-label extension study of a phase III, randomized, double-blind, placebo-controlled trial
Article first published online: 22 FEB 2014
Wiley Periodicals, Inc. © 2014 International League Against Epilepsy
Volume 55, Issue 4, pages 568–578, April 2014
How to Cite
Epilepsia, 55(4):568–578, 2014
- Issue published online: 22 APR 2014
- Article first published online: 22 FEB 2014
- Manuscript Accepted: 3 JAN 2014
- Eisai Ltd
- Italian Ministry of Health
- European Community Sixth Framework Thematic Priority Life Sciences
- Genomics and Biotechnology for Health
- E-Rare EU
- Italian Ministry of Education
- University and Research
- Tuscany Region
- Pisa Foundation
- Telethon Foundation
- Mariani Foundation
- Partial seizures;
- Pediatric epilepsy;
To investigate the safety/tolerability and efficacy of long-term adjunctive zonisamide and its impact on growth and development in children (6–18 years) with partial epilepsy.
Open-label extension of a phase III, placebo-controlled trial. Started with double-blind transition period (2–11 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 (maximum 500 mg/day). During the subsequent open-label period (45–57 weeks), zonisamide dosing could be adjusted according to tolerability/response. Safety assessments included treatment-emergent adverse events (TEAEs), clinical laboratory parameters, and vital signs. Efficacy assessments included responder rate (primary assessment) and seizure freedom rate during the open-label period. Growth and development assessments comprised Tanner stages, hand x-rays, Child Behavior Checklist (CBCL 6/18), School Performance questionnaire, Physician and Parent/Guardian Global Impression of Change, and Controlled Oral Word Association Test (COWAT).
One hundred forty-four children entered the study; 99 (68.8%) of 144 children completed it, and 108 (75.0%) of 144 received zonisamide for ≥1 year. TEAEs occurred in 39 (27.1%) of 144 patients. There were low incidences of serious TEAEs (2.1%) and TEAEs leading to discontinuation (2.8%). Bicarbonate level decreases >3.5 mm occurred in 64 patients (44.4%), and 24 patients (16.7%) had a weight decrease of ≥10% from baseline. During the open-label period, 81 (56.3%) of 144 patients were responders and 16 (11.1%) of 144 achieved seizure freedom. Tanner staging and skeletal development were as expected for the study population. Changes were minimal for CBCL 6/18 and School Performance scores. Most patients were “much improved”/“very much improved” on Physician (73.8%) and Parent/Guardian (75.4%) Global Impressions of Change. Median changes in COWAT Category and Letter Fluency scores were 2.0 and 0.5, respectively.
Adjunctive zonisamide was well tolerated and efficacious over a period of at least 1 year in children with partial epilepsy, with no unexpected safety concerns and no consistent detrimental effects on growth and development.
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