Long-term safety and sustained efficacy of USL255 (topiramate extended-release capsules) in patients with refractory partial-onset seizures

作者：Chung Steve S^*; Hogan R Edward; Blatt Ilan; Balduin Lawson P; Nguyen Huy; Clark Annie M; Anders Bob; Halvorsen Mark B

来源：Epilepsy and Behavior, 2016, 59: 13-20.

DOI：10.1016/j.yebeh.2016.03.005

• Epilepsy
• Antiepileptic drug
• Qudexy (R) XR
• Open-label extension (OLE)
• PREVAIL
• Topiramate
• Extended release

Objective: The aim of this study was to evaluate long-term safety, efficacy, and quality of life (QOL) of <= 400-mg/day USL255, Qudexy (R) XR (topiramate) extended-release capsules, as adjunctive therapy for partial-onset seizures (POS) in adults.
Methods: Patients who completed the 11-week double-blind treatment phase of the phase 3 PREVAIL study were eligible to enroll in this 1-year open-label extension (OLE) study (PREVAIL OLE). The primary objective was to evaluate the safety and tolerability of USL255 (including treatment-emergent adverse events [TEAEs]). The secondary objective was to assess seizure frequency in patients (e.g., median percent reduction from baseline in weekly POS frequency, responder rate [proportion of patients with >= 25%, >= 50%, >= 75%, or 100% reduction from baseline in POS frequency], and seizure-free intervals [proportion of patients who were seizure-free for 4, 12, 24, 36, or 48 weeks]). Exploratory clinical-status endpoints included the Global Impression of Change (CGI-C) and Quality of Life in Epilepsy-Problems (QOLIE-31-P) questionnaires. Post hoc analyses evaluated neurocognitive TEAE incidences during the first 11 and entire 55 weeks of treatment and efficacy by patient age and drug-resistant status.
Results: Of the 217 patients who completed PREVAIL (USL255, n = 103; placebo, n = 114), 210 (97%) enrolled in PREVAIL OLE and were included in the ITT population. Across the entire 55-week treatment period, USL255 was generally safe and well tolerated, with low individual neurocognitive TEAE incidences. Seizure reduction was sustained across the year-long study and observed in patient subgroups, including those with highly drug-resistant seizures and those = 50 years of age. Improvements in CGI-C and QOLIE-31-P were also observed.
Significance: The results of PREVAIL OLE are consistent with those from PREVAIL and demonstrate that adjunctive treatment with up to 400 mg/day of USL255 may be a safe and effective treatment option for a variety of adult patients with refractory POS.

• 出版日期2016-6