(Abst. 2.117 ), 2013
LONG-TERM OPEN-LABEL EXTENSION (OLE) STUDY EVALUATING THE SAFETY AND EFFICACY OF USL255, ONCE-DAILY EXTENDED-RELEASE TOPIRAMATE, IN PATIENTS WITH PARTIAL-ONSET SEIZURES: INTERIM ANALYSIS FROM PREVAIL OLE
Authors: T. A. Fakhoury, S. S. Chung, B. Anders, D. Laine, I. Blatt
USL255, a once-daily extended-release topiramate formulation, recently demonstrated efficacy and favorable tolerability as an adjunctive treatment for refractory partial-onset seizures (POS) in a randomized, double-blind, phase 3 clinical trial (PREVAIL; NCT01142193). The long-term effects of USL255 in this population are currently being evaluated in a 1-year open-label extension (OLE) study. Presented here are the interim safety and exposure data, as of 25 January 2013, following the completion of the PREVAIL trial by all subjects.
In this 1-year, global, phase 3, OLE study, the long-term safety and efficacy of USL255 as adjunctive therapy in patients with refractory POS are undergoing evaluation. Only subjects who completed the 11-week double-blind treatment phase from PREVAIL were eligible to enroll. Subjects opting to participate in the OLE study underwent a 3-week blinded conversion phase, where PREVAIL subjects randomized to placebo treatment were titrated to 200 mg/d USL255 by 50 mg/d each week, and those randomized to USL255 were titrated with matching placebo. This conversion phase was followed by a 52-week open-label treatment phase, where dose adjustments (up or down titrated by 50 mg/d weekly) were permitted after 8 weeks, as deemed necessary by the investigator, until an optimal dose was achieved (up to 400 mg/d). At the end of the open-label phase, subjects are then tapered off study drug by 50 mg/d each week over a minimum of 3 weeks. Safety and tolerability assessments include adverse event (AE) monitoring, laboratory evaluations, vital sign measurements, and physical examinations. Additional analyses include evaluation of POS frequency, Clinical Global Impression of Change (CGI-C) scores, and Quality of Life in Epilepsy – Problems (QOLIE-31-P) Survey.
Although the PREVAIL OLE study is ongoing, presented here are interim exposure and safety results. Of the 217 subjects who completed the PREVAIL trial, 210 (96.8%) elected to continue into the OLE study. As of 25 January 2013, 32 subjects (15.2%) had completed the year-long OLE study. A total of 17 subjects (8.1%) had discontinued due to AEs. Of the 15 serious adverse events (SAEs) experienced by 11 subjects, only 1 event of cholelithiasis that resolved with sequelae was deemed by the investigator as possibly related to USL255; all other events were deemed unrelated. These included 2 SAEs that resolved with sequelae (fibula fracture and tibia fracture) and 1 death resulting from ischemic stroke. The 11 remaining SAEs unrelated to treatment resolved without sequelae.
While the PREVAIL OLE study is ongoing, interim exposure and safety data suggest that USL255, at dosages up to 400 mg/d, is generally well tolerated as an adjunctive treatment for refractory partial-onset seizures. Supported by Upsher-Smith Laboratories, Inc.
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