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

Abstract Objective The aim of this study was to evaluate long-term safety, efficacy, and quality of life (QOL) of ≤ 400-mg/day USL255, Qudexy® 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.