Abstracts

Rationale: To assess long-term safety and efficacy information for patients, age 1 - 24 months, with all seizure types, including partial onset seizures (POS), exposed to topiramate at dosages up to 60 mg/kg/day for approximately 1 year. Methods: Data from the open-label extensions (OLE) of 2 international studies were pooled. Patients with clinical or vEEG evidence of refractory POS were enrolled in an. open-label treatment (OLT) phase of up to 6 wks or a 20-day double-blind (DB), placebo-controlled phase in the 2 studies.. Topiramate did not demonstrate efficacy in the DB phase and results of the OLT and DB phases are reported elsewhere. Patients who completed or discontinued from the first phase of each study could continue into the OLE. Also, patients ineligible for the DB study could enroll in the OLE. Patients were to be titrated to a dose of 25 mg/kg/day during the first 3 - 5 weeks in OLE and subsequently doses were uptitrated to the maximum tolerated, to seizure freedom, or to a maximum of 60 mg/kg/day, whichever occurred first. Efficacy was determined by reduction in seizure rate for POS and all seizure types from the pretreatment baseline to the endpoint of the OLE (recorded on patient take-home records). Efficacy was assessed in the ITT population: those who received ≥1 dose of study medication and had 1 postbaseline efficacy measurement in the OLE. Safety (clinical laboratory tests, physical/neurologic examinations, vital signs, growth measurements, renal ultrasounds, EKG, Vineland Scale of Adaptive Behavior assessments) was assessed in all patients who took ≥1 dose of study medication. Results: The ITT population (n = 284; mean age 12 months), was 54% boys, 62% white, 23% Asian. The median average topiramate dose was 21.4 (1.4; 55.2) mg/kg/day. From baseline to the endpoint of the OLE the overall median monthly POS rate decreased from 100.75 to 1.71 (91.6%) and the overall median monthly seizure rate (all types) decreased from 153.76 to 48.14 (82.0%). Safety was evaluated in the 284 patients who enrolled in the OLE. The most common adverse events were fever (52%), URI (51%), anorexia (35%), acidosis (31%), vomiting (28%), somnolence (27%), viral infection (26%), and diarrhea (24%). A total of 20 (7%) patients had adverse events leading to discontinuation; the most common event was aggravation of convulsions (n=6). A total of 115 (40%) patients had ≥1 serious adverse event; most did not lead to study discontinuation. Overall mean changes from pretreatment baseline to endpoint in Z-scores were -0.82 for body weight and -0.45 for body length. Conclusions: Topiramate at dosages up to 60 mg/kg/day was generally well tolerated. No safety concerns were identified that were specific to this age group and not seen in older patients. Both the median monthly POS rate and the median monthly seizure rate (all types) decreased from baseline. However, conclusions regarding efficacy are limited by the uncontrolled nature of the extension phase of the trials and the limitations of seizure log data.