(Abst. 2.116 ), 2013
USL255 IS EFFICACIOUS ACROSS ALL PARTIAL-ONSET SEIZURE TYPES AND WITH A VARIETY OF CONCOMITANT ANTIEPILEPTIC DRUGS: RESULTS FROM SUBGROUP ANALYSES OF THE PHASE 3 PREVAIL CLINICAL TRIAL
Authors: I. Blatt, V. N. Nagaraddi, B. Anders, A. M. Clark, M. B. Halvorsen, R. E. Hogan
Despite the armamentarium of available antiepileptic drugs (AEDs), approximately 30% of patients with partial-onset seizures (POS) continue to experience a variety of seizure types (eg, simple partial [SP], complex partial [CP], partial secondarily generalized [PSG]). USL255 is a once-daily extended-release topiramate formulation developed for the treatment of epilepsy. The phase 3 PREVAIL clinical trial (NCT01142193) demonstrated the efficacy and safety of USL255 as an adjunctive treatment for refractory POS. Presented here are the efficacy data by seizure type and concomitant AED use.
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. Median percent reduction from baseline in weekly POS frequency, as well as responder rate (defined as the proportion of subjects with ≥50% reduction in weekly POS frequency), were evaluated across all 11 weeks of double-blind treatment. Subgroup analyses were performed to evaluate the effects of USL255 by seizure type (SP with or without motor signs, CP, and PSG) and by concomitant AEDs (number of concomitant AEDs, lifetime AED use, and enzyme inducer status).
All 249 subjects randomized to treatment (n=124 USL255; n=125 placebo) were included in these analyses. Overall, CP seizures were the most common type observed. When compared with placebo, USL255 significantly reduced median weekly CP seizure frequency (P=.001) and was associated with a higher responder rate (P=.003). Reduction in median weekly CP and PSG seizures combined was also improved in USL255-treated subjects compared with placebo (P<.001). USL255 demonstrated similar trends in seizure reduction for other POS types, although the numbers of subjects in these groups were low (<30/treatment group), and the study was not powered for these analyses. When evaluating efficacy by the number of concomitant AEDs, USL255 was most effective in subjects taking more than 2 AEDs. Similarly, when evaluating reduction from baseline in weekly POS frequency by number of lifetime AEDs used, USL255 demonstrated improvement, even in the most refractory subjects (≥7 AEDs tried). USL255 was effective in subjects concomitantly taking enzyme-inducing AEDs; however, the small number of subjects taking non-enzyme inducing AEDs (<15 subjects/treatment group) precluded an unequivocal analysis.
USL255 was efficacious in the adjunctive treatment of all types of POS, with a variety of concomitant AEDs, and in the most refractory of subjects. The results from the PREVAIL study demonstrate broad and consistent efficacy of USL255, which provides a significant benefit to patients with refractory partial epilepsy. Supported by Upsher-Smith Laboratories, Inc.
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