title: Long-term safety and sustained efficacy of USL255 (topiramate extended-release capsules) in patients with refractory partial-onset seizures.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Banner University Medical Center, Phoenix, AZ, USA. Electronic address: steve.chung@bannerhealth.com.
authors.forename: Steve S
authors.initials: SS
authors.lastname: Chung
authors.affiliation: Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: R Edward
authors.initials: RE
authors.lastname: Hogan
authors.affiliation: The Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Blatt
authors.affiliation: Hospital Dr. Sótero del Río, Oficina de Investigaciones Médicas, Puente Alto, Chile.
authors.forename: Balduin
authors.initials: B
authors.lastname: Lawson P
authors.affiliation: Upsher-Smith Laboratories, Inc., Maple Grove, MN, USA.
authors.forename: Huy
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Upsher-Smith Laboratories, Inc., Maple Grove, MN, USA.
authors.forename: Annie M
authors.initials: AM
authors.lastname: Clark
authors.affiliation: Upsher-Smith Laboratories, Inc., Maple Grove, MN, USA.
authors.forename: Bob
authors.initials: B
authors.lastname: Anders
authors.affiliation: Upsher-Smith Laboratories, Inc., Maple Grove, MN, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Halvorsen
mesh_terms: D000328:Adult; D000375:Aging; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000139:chemically induced / Q000523:psychology; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy* / Q000523:psychology; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011788:Quality of Life; D012640:Seizures / Q000188:drug therapy* / Q000523:psychology; D011795:Surveys and Questionnaires; D000077236:Topiramate; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D000077236:Topiramate; D005632:Fructose
keywords: Antiepileptic drug; Epilepsy; Extended release; Open-label extension (OLE); PREVAIL; Qudexy® XR; Topiramate