Abstracts

Rationale: USL255, Qudexy™ (topiramate) extended-release capsules, was recently approved as a once-daily treatment for epilepsy and demonstrated efficacy for adjunctive treatment of refractory partial-onset seizures (POS) in the phase 3 PREVAIL study (NCT01142193). Long-term safety and efficacy of USL255 was evaluated in a 1-year, global, PREVAIL open-label extension (OLE; NCT01191086) study. Described here are long-term investigator- and patient-based assessments of clinical status and quality of life (QoL). Methods: In PREVAIL, adults with POS (N=249) were randomized to USL255 (n=124) or placebo (n=125). USL255-treated patients were titrated to 200 mg/d over 3 weeks (50 mg/wk) and maintained at this dosage for 8 weeks. Of the patients who completed PREVAIL, 210 enrolled in the OLE. During a 3-week blinded conversion phase in the OLE, patients randomized to placebo in PREVAIL (n=111) were titrated to 200 mg/d USL255 and maintained for 8 weeks; those randomized to 200 mg/d USL255 in PREVAIL (n=99) were given matching placebo. Following 11 weeks of treatment, USL255 dosage could be down- or up-titrated (max 400 mg/d). Investigators used the Clinical Global Impression of Change (CGI-C) scale to evaluate change from baseline in seizure severity, frequency, and overall functional status. Patients evaluated their own health-related QoL using the Quality of Life in Epilepsy-Problems (QOLIE-31-P) survey, wherein a greater change from baseline score indicated higher positive change in QoL. Baseline was the 8-week period prior to the start of treatment in PREVAIL. Change from baseline was assessed after the first 11 weeks of PREVAIL and OLE and at Week 55 (or early termination [ET]) of the OLE. Results: A total of 148 patients completed the OLE. Of the 92 patients with CGI-C assessments at Week 55/ET, 45 (49%) were rated as ‘very much' or ‘much improved.' In patients newly exposed to USL255 in the OLE, 41% (42/102) were ‘very much/much improved' after the first 11 weeks, similar to the 38% (45/119) of USL255-treated patients during PREVAIL. At Week 55/ET, mean change from baseline in the overall QOLIE-31-P score was 5.0 (n=88); similar changes from baseline were reported in newly exposed USL255-treated patients after Week 11 of the OLE (2.9 [n=97]) and PREVAIL (5.2 [n=100]). The largest observed change at Week 55 was in the QOLIE-31-P ‘seizure worry' subscale (10.8), which assesses the impact of seizures on QoL. This subscale was similarly increased in patients newly exposed to USL255 after 11 weeks in the OLE and PREVAIL. Conclusions: During the PREVAIL OLE, clinicians and patients reported improvements in clinical status (CGI-C) and the QOLIE-31-P seizure worry subscale during 1 year of treatment with up to 400 mg/d USL255. These long-term results confirm the persistence of effects observed in the PREVAIL study and, combined with safety and efficacy findings from the OLE, suggest that USL255 may be a useful treatment option for long-term management of epilepsy. Supported by Upsher-Smith Laboratories, Inc.