Long-term safety and sustained efficacy of USL255 (topiramate extended-release capsules) in patients with refractory partial-onset seizures

Epilepsy Behav. 2016 Jun;59:13-20. doi: 10.1016/j.yebeh.2016.03.005. Epub 2016 Apr 14.

Abstract

Objective: The aim of this study was to evaluate long-term safety, efficacy, and quality of life (QOL) of ≤400-mg/day USL255, Qudexy® XR (topiramate) extended-release capsules, as adjunctive therapy for partial-onset seizures (POS) in adults.

Methods: Patients who completed the 11-week double-blind treatment phase of the phase 3 PREVAIL study were eligible to enroll in this 1-year open-label extension (OLE) study (PREVAIL OLE). The primary objective was to evaluate the safety and tolerability of USL255 (including treatment-emergent adverse events [TEAEs]). The secondary objective was to assess seizure frequency in patients (e.g., median percent reduction from baseline in weekly POS frequency, responder rate [proportion of patients with ≥25%, ≥50%, ≥75%, or 100% reduction from baseline in POS frequency], and seizure-free intervals [proportion of patients who were seizure-free for 4, 12, 24, 36, or 48weeks]). Exploratory clinical-status endpoints included the Global Impression of Change (CGI-C) and Quality of Life in Epilepsy-Problems (QOLIE-31-P) questionnaires. Post hoc analyses evaluated neurocognitive TEAE incidences during the first 11 and entire 55weeks of treatment and efficacy by patient age and drug-resistant status.

Results: Of the 217 patients who completed PREVAIL (USL255, n=103; placebo, n=114), 210 (97%) enrolled in PREVAIL OLE and were included in the ITT population. Across the entire 55-week treatment period, USL255 was generally safe and well tolerated, with low individual neurocognitive TEAE incidences. Seizure reduction was sustained across the year-long study and observed in patient subgroups, including those with highly drug-resistant seizures and those ≥50years of age. Improvements in CGI-C and QOLIE-31-P were also observed.

Significance: The results of PREVAIL OLE are consistent with those from PREVAIL and demonstrate that adjunctive treatment with up to 400mg/day of USL255 may be a safe and effective treatment option for a variety of adult patients with refractory POS.

Trial registration: ClinicalTrials.gov NCT01191086.

Keywords: Antiepileptic drug; Epilepsy; Extended release; Open-label extension (OLE); PREVAIL; Qudexy® XR; Topiramate.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aging
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / psychology
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Resistant Epilepsy / drug therapy*
  • Drug Resistant Epilepsy / psychology
  • Epilepsies, Partial / drug therapy*
  • Female
  • Fructose / administration & dosage
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Fructose / therapeutic use
  • Humans
  • Male
  • Quality of Life
  • Seizures / drug therapy*
  • Seizures / psychology
  • Surveys and Questionnaires
  • Topiramate
  • Treatment Outcome

Substances

  • Anticonvulsants
  • Delayed-Action Preparations
  • Topiramate
  • Fructose

Associated data

  • ClinicalTrials.gov/NCT01191086