Early Onset of Efficacy and Safety Outcomes with USL255 Treatment: The PREVAIL Study (P3.264)

OBJECTIVE: Evaluate early efficacy and timing of treatment-emergent adverse events (TEAEs) with USL255, a once-daily extended-release topiramate formulation. BACKGROUND: Since many antiepileptic drugs require titration to achieve effective doses, it may be helpful to understand how quickly patients may experience symptom improvement after starting treatment. DESIGN/METHODS: In this double-blind, phase 3 study (PREVAIL; NCT01142193), participants with partial-onset seizures (POS) on 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. Efficacy endpoints included median percent reduction from baseline in weekly POS frequency and 50% responder rate during titration and maintenance phases separately. Post-hoc analyses included weekly seizure reduction and TEAEs by phase. RESULTS: During titration, USL255 was associated with significant reductions in weekly POS frequency vs placebo (34% vs 8.6%; P P =.001). During titration, 50% responder rate was significantly greater following USL255 treatment (34% vs 18%; P =.007); similar results were observed during maintenance (44% vs 31%; P =.048). When evaluated weekly, POS frequency was significantly reduced as early as Week 1 with USL255 (29% vs 9.2%; P <.05). Incidence of TEAEs was highest during titration for both USL255 (50%) and placebo (31%). After the first 4 weeks of maintenance, there was a 2% difference in TEAE incidence between USL255 (26%) and placebo (24%). Similar results were seen for nervous system disorder TEAEs, including neurocognitive and neuropsychiatric events, most of which resolved during maintenance. CONCLUSIONS: USL255 demonstrated significant efficacy as early as the first week of treatment (50 mg/day), with sustained benefit throughout the study. Incidence of TEAEs was higher in the titration than maintenance phase. USL255 demonstrated an early onset of efficacy, with TEAE rates similar to placebo after 4 weeks of maintenance treatment. Study Supported by: Upsher-Smith Laboratories, Inc. Disclosure: Dr. Nagaraddi has received personal compensation for activities with Upsher-Smith Laboratories as a consultant, and with UCB Biosciences as a speaker. Dr. Nagaraddi has received research support from Upsher-Smith Laboratories and UCB Biosciences. Dr. Chung has received personal compensation for activities with UCB Pharma, Supermus, Esai Inc., Lundbeck Research USA, Inc., Upshire-Smith, and SK Life Science. Dr. Arnold has received personal compensation for activities with UCB Pharma, Upsher-Smith, and Eisai Inc. as a consultant. Dr. Clark has received personal compensation for activities with Upsher-Smith Laboratories, Inc. Dr. Anders has received personal compensation for activities with Upsher-Smith Laboratories, Inc. 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.