Abstracts

RATIONALE: Zonisamide (ZNS, Zonegran[reg]) is a broad-spectrum antiepilepsy drug (AED) approved in the United States for adjunctive treatment of partial seizures in adults with epilepsy. This study was designed to assess the safety and efficacy of ZNS in adults and children with primary generalized epilepsy.
METHODS: This open-label study included males and females [gte]5 years of age with a diagnosis of primary generalized epilepsy. Patients had to have seizures refractory to other AEDs and could not have a diagnosis of secondary generalized epilepsy from complex partial seizures. Initial ZNS dosages were based on patient body weight (12.5 mg/d for patients [lte]40 kg, 25 mg/d for patients [gt]40 kg); dosages were then titrated over 8 weeks to a maximum of 600 mg/d. Patients then completed an 8-week treatment period. Efficacy was assessed via changes from baseline to week 16 in type, duration, and frequency of seizures; patient and investigator global assessments (GAs); and quality of life (QOL) questionnaires. Safety was assessed via analysis of adverse events (AEs).
RESULTS: Ten females and 9 males (mean age=21 years, range=4 to 50 years) entered the study and received at least 1 ZNS dose; 7 patients completed the study. Two patients withdrew for inefficacy, and 1 withdrew due to AEs. Nine patients are still ongoing in the study. Mean ZNS dosage for the completers was 297 mg/d. Responder (ie, patients with a [gte]50% seizure frequency reduction) numbers for each seizure type were 3/5 for absence, 2/4 for tonic-clonic, 2/3 for myoclonic, 1/1 for tonic, and 2/7 for all seizures. For patient GAs, 4 patients (57.1%) showed improvement in current AED therapy, and 1 patient (14.3%) showed improvement in overall well-being. Six (85.7%) patients showed improvement on the investigator GA of current AED therapy. Three patients (42.9%) showed improvement on general QOL. Fourteen patients (73.7%) experienced [gte]1 ZNS-related AE; most common AEs included headache (21.1%), somnolence (15.8%), diarrhea (15.8%), central nervous system depression (15.8%), and fever (15.8%). Two serious AEs were reported: moderate tension headache (n=1) and fever, abdominal pain, weight loss, and elevated alkaline phosphatase (n=1). The latter AEs resulted in withdrawal of the patient from the study. Fever, weight loss, and abdominal pain improved with discontinuation of ZNS. Slightly elevated alkaline phosphatase levels existed in this patient prior to ZNS initiation and were not thought to be attributable to ZNS.
CONCLUSIONS: These preliminary data suggest ZNS may be effective in some patients with primary generalized epilepsy and is safe and well tolerated. Further studies of ZNS in this patient population are warranted.
[Supported by: Elan Pharmaceuticals, Inc.]; (Disclosure: Grant - Elan Pharmaceuticals, Honoraria - Elan Pharmaceuticals)