Long-Term Open-Label Extension (OLE) Study Evaluating USL255, Once-Daily Extended-Release Topiramate, in Patients With Partial Onset Seizures: Interim Analysis From PREVAIL OLE (P3.284)

OBJECTIVE: Evaluate interim data from a long-term study of USL255, once-daily extended-release topiramate, for the adjunctive treatment of refractory partial-onset seizures (POS). BACKGROUND: USL255 demonstrated efficacy and favorable safety/tolerability in a double-blind, placebo-controlled, phase 3 study (PREVAIL; NCT01142193). Interim data from the PREVAIL open-label extension (OLE) study (NCT01191086) are presented here. DESIGN/METHODS: Interim analyses (cutoff date 1 July 2013) of an ongoing OLE study of USL255 in adult patients with POS on 1-3 concomitant AEDs were performed. Patients who completed the 11-week double-blind phase from PREVAIL were eligible to enroll in the OLE. The OLE consisted of a 3-week blinded conversion phase (to 200 mg/day USL255), a 52-week open-label treatment phase, and a down titration of at least 3 weeks. USL255 dose adjustments of 50 mg/week were permitted after 11 weeks, until an optimal dose was achieved (maximum 400 mg/day); AED adjustments were also allowed following 11 weeks of treatment. Safety assessments included treatment-emergent adverse event (TEAE) monitoring. RESULTS: Of the 217 patients who completed PREVAIL, 210 (96.8%) elected to continue into the OLE study. As of the interim cutoff date, approximately 33 months after study start, data were available for 209 patients: 91 (43.5%) completed the year-long study, 70 (33.5%) were continuing treatment, and 48 (23%) had discontinued. Mean and median drug exposure for all patients were 283 and 347 days, respectively. A total of 18 (8.6%) patients discontinued due to a TEAE. The most common TEAEs were decreased weight (7.2%), headache (7.2%), somnolence (7.2%), and dizziness (5.7%). A total of 13 patients (6.2%) had at least 1 serious adverse event; of those only cholelithiasis (n=2) and status epilepticus (n=2) occurred in more than 1 patient. CONCLUSIONS: Interim exposure and safety data suggest that USL255, at dosages up to 400 mg/day, is generally well tolerated as an adjunctive treatment for refractory partial-onset seizures. Study Supported by: Upsher-Smith Laboratories, Inc. Disclosure: 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. Hogan has received research support from Eisai Inc., and Upsher Smith. Dr. Blatt has received personal compensation for activities with Upsher-Smith and GlaxoSmithKline, Inc. 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. Anders has received personal compensation for activities with Upsher-Smith Laboratories, Inc.