Abstracts

This study investigated the long-term safety of zonisamide in pediatric patients with epilepsy. This phase II, open-label extension study evaluated the long-term safety of zonisamide in pediatric patients who had begun zonisamide therapy in a previous clinical study. Patients were grouped based on their age at time of entry into the initial study: Group 1 (5-11 years) and Group 2 (12-18 years). Patients were maintained on their stable zonisamide dosage that was established during the initial study and were evaluated monthly for the first 3 months of the study, and again at 6 months, with additional visits at Month 9 and/or Month 12 for patients continuing treatment beyond Month 6. Study data were summarized through Month 12. Safety was evaluated via reported and observed adverse events (AEs), use of concomitant medications, and results of clinical laboratory measurements, vital signs, physical examinations, and electrocardiograms (ECGs). Twenty-nine patients (17 male and 12 female) enrolled and received zonisamide, including 20 in Group 1 and 9 in Group 2. The mean dosage ranged from 9.0 to 12.9 mg/kg per day; mean exposure to zonisamide was 259 days. Mean cumulative exposure during the initial and extension studies was 323 days. All patients received at least 1 concomitant antiepileptic medication during the study; no meaningful conclusions could be drawn regarding concomitant medication differences between age groups due to small sample size. All patients reported at least 1 AE, most being mild or moderate in severity. Convulsions and somnolence were more common ([gt]15% difference in frequency) in Group 1. Vomiting, weight loss, confusion, and thinking abnormal were more common in Group 2; however, the small number of patients and unequal distribution between age groups precluded any conclusions regarding age-related differences in AE frequency. Twenty-four patients (82.8%) reported AEs considered related to zonisamide. Treatment-related AEs (many of which were transient) reported in [gt]15% of patients were anorexia (37.9%), somnolence (34.5%), and asthenia (24.1%). Five patients (17.2%) reported a total of 11 nonfatal serious AEs (SAEs); 2 SAEs (encephalopathy and grand mal convulsion) were considered zonisamide related. There were no discontinuations due to AEs and no deaths. Few patients had clinically significant laboratory abnormalities; no patients discontinued due to laboratory abnormalities. Overall, 75% of patients had bicarbonate levels that were below the normal reference range and 28.6% of patients had chloride values that were above the normal reference range at any time during the study. Vital signs, physical examinations, and ECG results were generally unremarkable. Long-term zonisamide use was generally safe and well tolerated in this group of pediatric epilepsy patients. (Supported by Eisai Inc.)