Abstracts

Rationale: USL255, Qudexy™ XR (topiramate) extended-release capsules, was recently approved as a once-daily treatment for epilepsy. In an 11-week randomized, double-blind, placebo-controlled, global, phase 3 study (PREVAIL; NCT01142193), USL255 demonstrated efficacy and favorable tolerability for the adjunctive treatment of refractory partial-onset seizures (POS). Long-term safety and efficacy of USL255 was evaluated in a 1-year PREVAIL open-label extension (OLE; NCT01191086) study. Efficacy results during the first 11 weeks for patients newly exposed to USL255 in the OLE are compared with the results from patients randomized to USL255 for 11 weeks during PREVAIL. 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 217 patients who completed the 11-week double-blind treatment in PREVAIL (USL255 n=103; placebo n=114), 96.8% enrolled in the OLE. Using the same design as PREVAIL, patients previously randomized to placebo (n=111) were titrated to USL255 200 mg/d during a 3-week OLE blinded-conversion phase, and maintained at this dosage for 8 weeks. In both studies, change in concomitant antiepileptic drugs and USL255 dosage were not allowed during the first 11 weeks. Efficacy assessments included median percent reduction from baseline in weekly POS frequency and 50% responder rate (proportion of patients with ≥50% reduction in weekly POS frequency). Baseline for both PREVAIL and the OLE was the 8-week period prior to the start of treatment in PREVAIL. Results: Median percent reduction in seizure frequency following USL255 treatment was 40% during the 11 weeks of PREVAIL (n=124) and 56% during the first 11 weeks of the OLE (n=111). In both studies, reduced seizure frequency was already observed within the first week of USL255 treatment (29% of patients in PREVAIL and 66% in OLE) and was maintained for the remaining 10 weeks (range: 38%-79% for both studies). Similar trends were observed for 50% responder rate, which was 38% and 58% following 11 weeks of treatment in PREVAIL and OLE, respectively. In week 1, responder rate was 37% for PREVAIL and 63% for the OLE and ranged between 41% and 66% for the remaining 10 weeks of both studies. Conclusions: Once-daily USL255 was efficacious both in patients newly exposed to USL255 in the OLE and those randomized to active treatment during PREVAIL; variability in efficacy between these 2 groups may be due to inherent differences in study design. Efficacy was observed early and maintained throughout the 11-week USL255 treatment periods. These data confirm that adjunctive USL255 treatment may provide significant benefit to patients with epilepsy. Supported by Upsher-Smith Laboratories, Inc.