Abstracts

Rationale: USL255, Qudexy® XR (topiramate) extended-release capsules, is approved in patients ≥2 years of age as monotherapy and adjunctive therapy for the treatment of certain seizure types. Two phase 3 clinical trials, PREVAIL (NCT01142193) and PREVAIL open-label extension (OLE; NCT01191086), demonstrated that USL255 was well tolerated and efficacious as adjunctive treatment in patients with refractory partial-onset seizures (POS). Presented here are PREVAIL OLE post hoc efficacy analyses by patient refractory status and age.Methods: Patients on 1-3 concomitant antiepileptic drugs (AEDs) who completed the 11-week double-blind treatment phase from PREVAIL were eligible to enroll in the OLE. Participants (N=210) underwent a 3-week blinded-conversion phase, where patients randomized to placebo in PREVAIL were titrated to 200 mg/d USL255 (50 mg/week) and those randomized to 200 mg/d USL255 in PREVAIL maintained treatment and were given matching placebo. The conversion phase was followed by a 52-week open-label (OL) treatment phase. After 11 weeks of treatment, changes in USL255 dosage (50 mg/week up to 400 mg/d maximum) and concomitant AEDs were allowed. Post hoc efficacy analyses included median percent reduction from PREVAIL baseline in weekly POS frequency and responder rate (proportion of subjects with ≥50% reduction in POS frequency from PREVAIL baseline) by patient age and by highly vs less refractory status. Highly refractory status was defined as ≥2 concurrent AEDs and ≥4 lifetime AEDs, while less refractory patients were those with 1 concurrent AED or <4 lifetime AEDs.Results: Of the 210 patients enrolled, 148 patients (70%) completed the OLE. For all patients, median percent reduction in POS frequency and responder rate were 56% and 58%, respectively, during the 55-week OLE (conversion + OL phase). Seizure reduction was observed regardless of refractory subtype; for highly refractory (n=95) and less refractory (n=115) subgroups, median percent reductions in weekly POS frequency were 48% and 65%, respectively, and responder rates were 48% and 66%. Efficacy rates were also similar between the following age groups: 18-<35 (n=94), 35-<50 (n=84), and ≥50 years (n=31). Median percent reductions in weekly POS frequency in the 18-<35 years of age, 35-<50 years of age, and ≥50 years of age subgroups were 64%, 53%, and 52%, respectively; responder rates were 62%, 56%, and 52%.Conclusions: In this 1-year open-label extension study, USL255, up to 400 mg, was an effective adjunctive therapy for refractory POS patients, including those deemed highly refractory to treatment. In addition, efficacy was observed across different age groups, demonstrating that USL255 is a valuable treatment option for a variety of patients with epilepsy. Support: Upsher-Smith Laboratories, Inc.