TY - JOUR
T1 - Post hoc analysis of a phase 3, multicenter, open-label study of cenobamate for treatment of uncontrolled focal seizures
T2 - Effects of dose adjustments of concomitant antiseizure medications
AU - Rosenfeld, William E.
AU - Abou-Khalil, Bassel
AU - Aboumatar, Sami
AU - Bhatia, Perminder
AU - Biton, Victor
AU - Krauss, Gregory L.
AU - Sperling, Michael R.
AU - Vossler, David G.
AU - Klein, Pavel
AU - Wechsler, Robert
N1 - Funding Information:
This study was funded by SK Life Science, Inc. Medical writing and editorial assistance were provided by Debika Chatterjea, PhD, and Don Fallon, ELS, of MedVal Scientific Information Services, LLC (Princeton, NJ, USA), and were funded by SK Life Science, Inc. This manuscript was prepared according to the International Society for Medical Publication Professionals’ “Good Publication Practice for Communicating Company‐Sponsored Medical Research: GPP3.”
Publisher Copyright:
© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy
PY - 2021/12
Y1 - 2021/12
N2 - Objective: To report post hoc results on how adjustments to baseline antiseizure medications (ASMs) in a subset of study sites (10 US sites) from a long-term, open-label phase 3 study of adjunctive cenobamate affected tolerability, efficacy, and retention. Methods: Patients with uncontrolled focal seizures taking stable doses of one to three ASMs were administered increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals (target dose = 200 mg/day). Further increases to 400 mg/day by 50 mg/day biweekly increments were allowed during maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed. Data were assessed until last visit, at data cut-off, on or after September 1, 2019. Results: A total of 240 patients meeting eligibility criteria were assessed (median [max] exposure 30.2 [43.0] months), with 177 patients continuing cenobamate at data cut-off. Most common baseline concomitant ASMs were lacosamide, levetiracetam, lamotrigine, zonisamide, and clobazam. For most baseline concomitant ASMs, ~70% of patients taking that ASM were continuing cenobamate at data cut-off. Patients continuing cenobamate had greater mean ASM dose reductions and percent dose changes from baseline vs those who discontinued. Of patients continuing cenobamate, 24.6% discontinued one or more concomitant ASMs completely. Dose decreases for all concomitant ASMs generally occurred during titration or early maintenance phases and were mostly due to central nervous system (CNS)–related adverse events such as somnolence, dizziness, unsteady gait, and fatigue. Responder rates from ≥50% through 100% for patients continuing cenobamate were generally similar regardless of concomitant ASMs (of those most commonly taken), with ~81% being ≥50% responders and ~12% achieving 100% seizure reduction in the maintenance phase, which lasted up to 40.2 (median = 29.5) months. Significance: Concomitant ASM dose reductions were associated with more patients remaining on cenobamate. This is likely due to efficacy and improved tolerability, with overall reduced concomitant drug burden in patients with uncontrolled seizures despite taking one to three baseline concomitant ASMs.
AB - Objective: To report post hoc results on how adjustments to baseline antiseizure medications (ASMs) in a subset of study sites (10 US sites) from a long-term, open-label phase 3 study of adjunctive cenobamate affected tolerability, efficacy, and retention. Methods: Patients with uncontrolled focal seizures taking stable doses of one to three ASMs were administered increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals (target dose = 200 mg/day). Further increases to 400 mg/day by 50 mg/day biweekly increments were allowed during maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed. Data were assessed until last visit, at data cut-off, on or after September 1, 2019. Results: A total of 240 patients meeting eligibility criteria were assessed (median [max] exposure 30.2 [43.0] months), with 177 patients continuing cenobamate at data cut-off. Most common baseline concomitant ASMs were lacosamide, levetiracetam, lamotrigine, zonisamide, and clobazam. For most baseline concomitant ASMs, ~70% of patients taking that ASM were continuing cenobamate at data cut-off. Patients continuing cenobamate had greater mean ASM dose reductions and percent dose changes from baseline vs those who discontinued. Of patients continuing cenobamate, 24.6% discontinued one or more concomitant ASMs completely. Dose decreases for all concomitant ASMs generally occurred during titration or early maintenance phases and were mostly due to central nervous system (CNS)–related adverse events such as somnolence, dizziness, unsteady gait, and fatigue. Responder rates from ≥50% through 100% for patients continuing cenobamate were generally similar regardless of concomitant ASMs (of those most commonly taken), with ~81% being ≥50% responders and ~12% achieving 100% seizure reduction in the maintenance phase, which lasted up to 40.2 (median = 29.5) months. Significance: Concomitant ASM dose reductions were associated with more patients remaining on cenobamate. This is likely due to efficacy and improved tolerability, with overall reduced concomitant drug burden in patients with uncontrolled seizures despite taking one to three baseline concomitant ASMs.
KW - antiepileptics
KW - antiseizure medications
KW - cenobamate
KW - concomitant medications
KW - focal epilepsy
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U2 - 10.1111/epi.17092
DO - 10.1111/epi.17092
M3 - Article
C2 - 34633074
AN - SCOPUS:85116812398
VL - 62
SP - 3016
EP - 3028
JO - Epilepsia
JF - Epilepsia
SN - 0013-9580
IS - 12
ER -