Long-term safety and efficacy of zonisamide versus carbamazepine monotherapy for treatment of partial seizures in adults with newly diagnosed epilepsy: results of a phase III, randomized, double-blind study.

OBJECTIVE

To investigate the long-term safety and maintenance of efficacy of monotherapy with once-daily zonisamide versus twice-daily controlled-release carbamazepine for partial seizures in adults with newly diagnosed epilepsy.

METHODS

Long-term, double-blind, extension study, conducted in patients completing a phase III noninferiority trial comparing zonisamide and carbamazepine monotherapy. Patients continued their randomized treatment, with dosing adjusted according to tolerability/response (zonisamide 200-500 mg/day; carbamazepine 400-1,200 mg/day). Safety assessments included treatment-emergent adverse events (TEAEs) and clinical laboratory parameters. Efficacy assessments included retention rate and the proportion of patients remaining seizure free for ≥24 months.

RESULTS

Overall, 120 (87.6%) of 137 patients randomized to zonisamide and 134 (84.8%) of 158 patients randomized to carbamazepine completed the study. More than three-fourths of patients were exposed to >24 months of treatment. For zonisamide versus carbamazepine, incidences were similar for TEAEs (52.6% vs. 46.2%), serious treatment-related TEAEs (0.7% vs. 1.9%), and TEAEs leading to withdrawal (1.5% vs. 0.6%). The incidence of treatment-related TEAEs was 26.3% for zonisamide compared with 19.6% for carbamazepine, and the most frequently reported treatment-related TEAEs were decreased weight (5.1% vs. 0%), decreased appetite (3.6% vs. 0%), memory impairment (2.9% vs. 3.2%), and decreased hemoglobin level (1.5% vs. 3.2%). Most TEAEs were of mild or moderate intensity. There were no reports of Stevens-Johnson syndrome or toxic epidermal necrolysis in either group. Zonisamide was associated with small-to-moderate decreases in bicarbonate levels from baseline (mean -3.4 mm). There were no reports of metabolic acidosis. Retention rates were generally similar between treatment groups at all time points throughout the extension study. The proportion of patients remaining seizure free for ≥ 24 months was also similar for zonisamide (32.3%) and carbamazepine (35.2%).

SIGNIFICANCE

Once-daily zonisamide monotherapy demonstrated favorable long-term safety and maintenance of efficacy in treating partial seizures in adults with newly diagnosed epilepsy. No new or unexpected safety findings emerged.