Abstracts

This open-label study assessed the efficacy and safety of low-dose zonisamide initiated in combination with concomitant antiepileptic drugs (AEDs). Patients aged [ge]12 years with partial seizures treated with 1 or 2 concomitant AEDs were enrolled in a 4-week screening phase (SP). Patients were required to have [ge]1 seizure during the SP to be eligible for the study. Zonisamide was initiated at a dosage of 25 mg/d and increased to a maximum tolerated dosage or 400 mg/d during the titration phase (TP) (Weeks 0-8). Patients then received their maximum tolerated dosage for the maintenance phase (MP) (Weeks 9-12). The primary efficacy measure was seizure frequency per 28 days as recorded in a seizure diary. Secondary efficacy measures were the change in seizure type or duration and in physician and patient global assessments (rated on a 0-100 scale) between Week 0 (baseline) and Week 12. Safety was assessed via reports of adverse events (AEs) and changes in body weight. A total of 243 patients (mean age, 35.7 years; range, 12-85 years) were treated. Median duration of treatment was 84 days (range, 1-162 days); median maximum zonisamide dosage was 400 mg/d (range, 25-800 mg/d). Median seizure frequency decreased by 47.6% from 8.3 (SP) to 4.0 (MP), with 48.5% of patients (95% confidence interval [CI]: 41.4, 55.5) experiencing [ge]50% seizure frequency reduction. Median frequencies of simple partial, complex partial, and other seizure types were reduced by 57.1%, 51.0%, and 96.1%, respectively. A [ge]50% reduction in frequency of simple partial, complex partial, and other seizure types was observed in 53.2%, 51.0%, and 69.7% of patients, respectively. No change in seizure type or duration was apparent with zonisamide therapy. Patients[apos] global assessment of AED therapy improved significantly from a mean score of 40.7 at baseline to 67.1 (95% CI: 63.1, 70.4) during treatment. Investigator global assessments of AED therapy also improved from a mean of 31.7 at baseline to 64.0 (95% CI: 61.3, 66.8) during treatment. The most frequently reported treatment-emergent AEs ([ge]10% of patients) included dizziness (17.3%), somnolence (17.3%), headache (14.0%), abnormal thinking (13.2%), asthenia (11.9%), anorexia (11.5%), accidental injury (11.1%), and nausea (10.7%). Thirteen patients (5.3%) experienced serious AEs (SAEs), 4 of whom had SAEs considered to be zonisamide related. Twenty-two patients (9.1%) withdrew from the study for AEs. Mean body weight decreased from baseline by 0.7 kg (95% CI: -1.1, -0.4) and 1.0 kg (95% CI: -1.3, -0.6) in the TP and MP, respectively. This low-dose, slow titration regimen for zonisamide resulted in substantially decreased seizure frequency, and a significant proportion of patients had a [ge]50% seizure frequency reduction. Zonisamide was also generally safe and well tolerated. Small but significant decreases in body weight were observed during the study. (Supported by Eisai Inc.)