Adverse Event Profile of USL255 in Patients with Refractory Partial-Onset Seizures: The PREVAIL Study (P3.262)

OBJECTIVE: Evaluate the adverse event profile of USL255, once-daily extended-release (XR) topiramate, in adults with refractory partial-onset seizures (POS). BACKGROUND: Treatment-emergent adverse events (TEAEs) affecting the central nervous system can be associated with antiepileptic drug (AED) treatment. Immediate-release (IR) topiramate is an AED that is efficacious for the management of epilepsy, but requires twice-daily dosing. USL255 can be given once daily, is pharmacokinetically equivalent to IR topiramate at the same daily dose, and has reduced plasma fluctuations, which may result in decreased incidence of TEAEs caused by high peak drug levels. DESIGN/METHODS: In this double-blind, phase 3 study (PREVAIL; NCT01142193), patients taking 1-3 concomitant AEDs were randomized to placebo (n=125) or USL255 (n=124), titrated over 3 weeks (50 mg/week), and maintained at 200 mg/day for 8 weeks. Incidence of spontaneously-reported TEAEs was assessed by study phase and severity. Neurocognitive adverse events were also summarized. RESULTS: Overall, the incidence of TEAEs was 66% with USL255 and 50% with placebo treatment ( P =.015), and the majority were mild-to-moderate in intensity. A higher proportion of patients reported TEAE onset during the 3-week titration phase than during the first or last 4 weeks of the maintenance phase. Somnolence, dizziness, paraesthesia, weight decrease, fatigue, and headache were the most commonly reported TEAEs. The proportion of patients reporting a neurocognitive/neuropsychiatric TEAE (eg, memory impairment, psychomotor slowing) was less than 3% in both treatment groups, with the exception of disturbance in attention (2.4% [USL255]; 3.2% [placebo]). A majority of these events resolved before completion of maintenance. No deaths were reported and none of the serious TEAEs with USL255 were considered treatment related (USL255, 1.6%; placebo, 1.6%). CONCLUSIONS: USL255 demonstrated a favorable adverse event profile in patients with refractory POS with low incidence of neurocognitive adverse events, suggesting USL255 may provide a significant benefit to patients with epilepsy. Study Supported by: Upsher-Smith Laboratories, Inc. Disclosure: Dr. Hogan has received research support from Eisai Inc., and Upsher Smith. Dr. Arnold has received personal compensation for activities with UCB Pharma, Upsher-Smith, and Eisai Inc. as a consultant. Dr. Fakhoury has received personal compensation for activities with UCB Pharma, Upsher Smith Laboratories, Supernus, and Sunovion Pharmaceuticals. Dr. Fakhoury has received research support from UCB Pharma, Sunovion Pharmaceuticals, Upsher Smith Laboratories, SK Life Science, and Westward Pharmaceuticals. Dr. Anders has received personal compensation for activities with Upsher-Smith Laboratories, Inc.