Abstracts

Rationale: As symptoms of refractory epilepsy can negatively impact a patient s life, a goal of antiepileptic drug (AED) therapy is to improve daily functioning. USL255, a once-daily extended-release topiramate formulation, recently demonstrated efficacy and safety for the adjunctive treatment of refractory partial-onset seizures (POS) in the PREVAIL phase 3 clinical trial (NCT01142193). The data presented here detail the investigator- and subject-based assessments of clinical improvement and quality of life (QoL) with USL255 compared to placebo.Methods: Adult subjects with POS (N=249) on 1-3 concomitant AEDs, reporting 8 seizures with a 21-day seizure-free period during an 8-week baseline phase, were randomized (1:1) to receive once-daily USL255 or placebo. Subjects were up-titrated by 50 mg/d each week over 3 weeks and maintained at 200 mg/d for 8 weeks with USL255 or matching placebo. Investigators used the Clinical Global Impression of Change (CGI-C) a validated, observer-rated, 7-point scale to evaluate improvement or change in the subject s seizure severity, frequency, and overall functional status from baseline (1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse). Subjects evaluated their own health-related QoL using the validated Quality of Life in Epilepsy Problems (QOLIE-31-P) Survey. This 38-question survey is comprised of 7 subscales covering general and epilepsy-specific domains, with larger changes from baseline in total or subscale scores indicating a higher QoL. The QOLIE-31-P was completed by subjects only in countries where it was available and validated for the spoken language(s). Results: For subjects in which the investigator completed the CGI-C assessment, the overall score was significantly improved in USL255-treated subjects (n=119) compared with subjects administered placebo (n=124). These results were not affected by age, race, gender, or geographic region (P<.001 for all). Further, an almost 2-fold higher percentage of subjects receiving USL255 had CGI-C scores corresponding to improvement (scores of 1 or 2) compared with placebo (37.8% vs 19.4%, respectively; P<.002). While the overall QOLIE-31-P score was not significantly different between treatment groups, the subscale that assessed the impact of seizures on QoL (seizure worry) was significantly improved in the USL255 group as compared with placebo (14.1 vs 4.1, P<.001). Additionally, QoL subscales related to tolerability (eg, cognition, mood, energy, and daily activities) showed no significant differences between the USL255-treated subjects compared with subjects administered placebo. Conclusions: Both clinicians and subjects reported that USL255, when administered for the adjunctive treatment of refractory POS, improved clinical outcomes and functional status without adversely affecting quality of life. Therefore, once-daily USL255 may provide significant benefits to patients with refractory epilepsy. Supported by Upsher-Smith Laboratories, Inc.