TY - JOUR
T1 - Long-term safety and sustained efficacy of USL255 (topiramate extended-release capsules) in patients with refractory partial-onset seizures
AU - on behalf of the PREVAIL OLE Study Group
AU - Chung, Steve S.
AU - Hogan, R. Edward
AU - Blatt, Ilan
AU - Lawson P., Balduin
AU - Nguyen, Huy
AU - Clark, Annie M.
AU - Anders, Bob
AU - Halvorsen, Mark B.
N1 - Funding Information:
This study was funded by Upsher-Smith Laboratories, Inc. ( ClinicalTrials.gov number: NCT01191086 ). The authors thank Patricia Wozniak at Advanced Clinical Services and Sutan Wu for assistance in analyzing the data for this study. Medical writing assistance by Sarah Prins, Ph.D. and editorial support by Jacqueline Benjamin, Ph.D. at Prescott Medical Communications Group (Chicago, IL) was supported by Upsher-Smith Laboratories. A full list of coinvestigators can be found in the Supplementary materials.
Funding Information:
Ilan Blatt has received consulting fees and research support from Upsher-Smith Laboratories, Inc. and GSK.
Funding Information:
Steve S. Chung has received consulting fees from UCB Pharma, Sunovion, Eisai, Lundbeck, and Upsher-Smith Laboratories, Inc. and research support from UCB Pharma, Eisai, Lundbeck, Medtronics, Upsher-Smith, Acorda, and SK Life Science.
Publisher Copyright:
© 2016 The Authors.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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 48 weeks]). 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 55 weeks 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 ≥. 50 years 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 400 mg/day of USL255 may be a safe and effective treatment option for a variety of adult patients with refractory POS.
AB - 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 48 weeks]). 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 55 weeks 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 ≥. 50 years 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 400 mg/day of USL255 may be a safe and effective treatment option for a variety of adult patients with refractory POS.
KW - Antiepileptic drug
KW - Epilepsy
KW - Extended release
KW - Open-label extension (OLE)
KW - PREVAIL
KW - Qudexy® XR
KW - Topiramate
UR - http://www.scopus.com/inward/record.url?scp=84962910679&partnerID=8YFLogxK
U2 - 10.1016/j.yebeh.2016.03.005
DO - 10.1016/j.yebeh.2016.03.005
M3 - Article
C2 - 27084978
AN - SCOPUS:84962910679
SN - 1525-5050
VL - 59
SP - 13
EP - 20
JO - Epilepsy and Behavior
JF - Epilepsy and Behavior
ER -