Abstracts

Rationale: Topiramate is an approved anticonvulsant for use in adults and pediatric population (2-16 years). However, its impact on factors influencing growth and maturation, metabolic acidosis, kidney stone formation in children with epilepsy has not been fully characterized.  As childhood is a crucial period for bone mineralization and growth, we designed a randomized, open-label (OL), flexible-dose, phase-4 study to systematically compare long-term safety of topiramate versus levetiracetam (active-comparator) monotherapy in children with epilepsy.   Methods: The study has 3 phases (Figure 1): screening (28-days), OL treatment (1-year), and posttreatment (30-days) phase with optional poststudy follow-up. Eligibility for children (2 to<16 years, approximately 282 planned) includes newly/recently diagnosed epilepsy in past 2-years (partial-onset seizures with/without secondary generalization or primary generalized tonic-clonic seizures); ≤1 unprovoked seizure within 3 months and evidence of appropriate physical development (weight and height values within 5^th−95^th percentile) at study entry; documented inadequacy with current anticonvulsant treatment. Children (age-stratified) will randomly (1:1) receive weight-based twice-daily dosing of either topiramate (350 mg/day: 2 to<10 years, 400 mg/day: 10 to<16 years) or levetiracetam (60 mg/kg/day: 2 to<16 years). Key safety evaluations: renal ultrasound, Dual Energy X-Ray Absorptiometry (DEXA) scan, Tanner staging, and biochemical bone markers. Key safety analyses: percentage of children with nephrolithiasis, changes from baseline in weight and height Z-scores, bone mineral density and content (also Z-scores) over time.   Results: Trial in progress (results awaited). Conclusions: This study design will allow evaluation of clinically important treatment-related effects of topiramate versus levetiracetam monotherapy in children and adolescents over 1-year duration in a real-world practice setting.