[P3.261] Efficacy, Safety, and Impact on Quality of Life of USL255 in Patients with Refractory Partial-Onset Seizures: The PREVAIL Study
Steve Chung,1Toufic Fakhoury,2Stephan Arnold,3Balduin Lawson,4Ilan Blatt,5Annie M. Clark,6Mark Halvorsen,6Venkatesh Nagaraddi,7Bob Anders6
1Phoenix, AZ, USA, 2Lexington, KY, USA, 3Münich, Germany, 4Santiago, Chile, 5Tel Hashomer, Israel, 6Maple Grove, MN, USA, 7Dallas, TX, USA
OBJECTIVE: Evaluate efficacy, safety, and impact on quality of life (QoL) of adjunctive treatment with USL255, once-daily extended-release (XR) topiramate, in adults with refractory partial-onset seizures (POS).
BACKGROUND: Treatment nonadherence, common in patients with epilepsy, can increase seizures and adversely affect QoL. Compared with immediate-release (IR) antiepileptic drugs (AEDs), XR formulations can improve adherence by reducing dosing frequency and may decrease treatment-emergent adverse events (TEAEs) caused by peak-dose toxicity. At the same daily dose, USL255 is pharmacokinetically equivalent to IR topiramate and reduces plasma fluctuations.
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. Primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and 50% responder rate following 11 weeks of treatment. Safety (TEAEs, laboratory findings, physical/neurological exams) and treatment effects on the Quality of Life in Epilepsy - Problems (QOLIE-31-P) and Clinical Global Impression-Change (CGI-C) scale were evaluated.
RESULTS: USL255 resulted in greater reduction in POS frequency (39.5% vs 21.6%, P<.001) and greater 50% responder rate (37.9% vs 23.2%, P=.013) vs placebo. TEAE incidence was 66% (USL255) and 50% (placebo) (P=.015). Less than 3% of USL255-treated patients reported individual neurocognitive or neuropsychiatric TEAEs. No serious AEs (1.6% each group) were deemed USL255 related, and there were no abnormal trends in safety evaluations. The QOLIE-31-P seizure-worry subscale was significantly improved (14.1 vs 4.1, P<.001) with USL255 vs placebo, though the overall score was not significantly different (5.2 vs 4.5). Almost twice as many USL255-treated patients had improved CGI-C scores (37.8% vs 19.4%; P<.002).
CONCLUSIONS: The PREVAIL study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control, was well tolerated with few neurocognitive/neuropsychiatric side effects, and may functionally benefit patients with epilepsy.
Study Supported by: Upsher-Smith Laboratories, Inc.
Category - Epilepsy and Clinical Neurophysiology (EEG): Therapeutics: Medical
Tuesday, April 29, 2014 3:00 PM
P3: Poster Session III: Epilepsy and Clinical Neurophysiology: AED (3:00 PM-6:30 PM)