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.

Abstract

OBJECTIVE:

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.

METHODS:

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).

RESULTS:

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.

SIGNIFICANCE:

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. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

• Authors: Renzo Guerrini, Anna Rosati, Kate Bradshaw, Luigi Giorgi
• Journal: Epilepsia (Epilepsia) Vol. 55 Issue 4 Pg. 568-78 (Apr 2014) ISSN: 1528-1167 [Electronic] United States
• PMID: 24621319 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Chemical References

• Anticonvulsants
• Isoxazoles
• Zonisamide

Topics

• Adolescent
• Anticonvulsants (administration & dosage)
• Child
• Double-Blind Method
• Epilepsies, Partial (diagnosis, drug therapy, physiopathology)
• Female
• Humans
• Isoxazoles (administration & dosage)
• Male
• Time Factors
• Treatment Outcome
• Zonisamide