TY - JOUR
T1 - Adjunctive eslicarbazepine acetate
T2 - A pooled analysis of three phase III trials
AU - On behalf of the Study 301, 302 and 304 Investigators
AU - Biton, Victor
AU - Rogin, Joanne B.
AU - Krauss, Gregory
AU - Abou-Khalil, Bassel
AU - Rocha, José F.
AU - Moreira, Joana
AU - Gama, Helena
AU - Trinka, Eugen
AU - Elger, Christian E.
AU - Cheng, Hailong
AU - Grinnell, Todd
AU - Blum, David
N1 - Funding Information:
Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA, and BIAL – Portela & Ca, S.A., São Mamede do Coronado, Portugal funded the clinical trials reported in this manuscript. The sponsors were involved in the study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication. Medical writing support was funded by Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA.
Publisher Copyright:
© 2017 The Authors
PY - 2017/7
Y1 - 2017/7
N2 - Objective To assess the safety and efficacy of once-daily (QD) adjunctive eslicarbazepine acetate (ESL). Methods This post-hoc pooled analysis of three randomized, placebo-controlled trials (2093-301, -302, -304) involved adults with refractory partial-onset seizures (POS) receiving 1–3 antiepileptic drugs (AEDs). All studies included 8-week baseline, 2-week titration, and 12-week maintenance periods. Patients were randomized equally to placebo, ESL 400 mg (studies 301, 302), 800 mg, or 1200 mg QD. The primary endpoint was standardized seizure frequency (SSF; per 4 weeks); secondary endpoints included responder rates (maintenance period), and incidence of treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation, serious AEs (SAEs), and deaths. Results The safety and efficacy analysis populations totaled 1447 and 1410 patients, respectively. SSF was significantly reduced versus placebo with ESL 800 mg (p = 0.0001) and 1200 mg (p < 0.0001) but not 400 mg (p = 0.81). There were no significant interactions between treatment effect and age, gender, race/ethnicity, geographic region, epilepsy duration, or concomitant AED use. Incidences of TEAEs and TEAEs leading to discontinuation increased with ESL dose. Incidences of the most frequent TEAEs were lower for patients who initiated dosing at 400 versus 800 mg QD, regardless of titration regimen and maintenance dose. SAE incidence was < 10%; there were 3 deaths (placebo, n = 2; ESL 800 mg, n = 1). Conclusions ESL (800 and 1200 mg QD) was effective and well tolerated as adjunctive therapy for adults with refractory POS.
AB - Objective To assess the safety and efficacy of once-daily (QD) adjunctive eslicarbazepine acetate (ESL). Methods This post-hoc pooled analysis of three randomized, placebo-controlled trials (2093-301, -302, -304) involved adults with refractory partial-onset seizures (POS) receiving 1–3 antiepileptic drugs (AEDs). All studies included 8-week baseline, 2-week titration, and 12-week maintenance periods. Patients were randomized equally to placebo, ESL 400 mg (studies 301, 302), 800 mg, or 1200 mg QD. The primary endpoint was standardized seizure frequency (SSF; per 4 weeks); secondary endpoints included responder rates (maintenance period), and incidence of treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation, serious AEs (SAEs), and deaths. Results The safety and efficacy analysis populations totaled 1447 and 1410 patients, respectively. SSF was significantly reduced versus placebo with ESL 800 mg (p = 0.0001) and 1200 mg (p < 0.0001) but not 400 mg (p = 0.81). There were no significant interactions between treatment effect and age, gender, race/ethnicity, geographic region, epilepsy duration, or concomitant AED use. Incidences of TEAEs and TEAEs leading to discontinuation increased with ESL dose. Incidences of the most frequent TEAEs were lower for patients who initiated dosing at 400 versus 800 mg QD, regardless of titration regimen and maintenance dose. SAE incidence was < 10%; there were 3 deaths (placebo, n = 2; ESL 800 mg, n = 1). Conclusions ESL (800 and 1200 mg QD) was effective and well tolerated as adjunctive therapy for adults with refractory POS.
KW - Antiepileptic drug
KW - Efficacy
KW - Eslicarbazepine acetate
KW - Partial-onset seizures
KW - Refractory epilepsy
KW - Tolerability
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U2 - 10.1016/j.yebeh.2017.04.019
DO - 10.1016/j.yebeh.2017.04.019
M3 - Article
C2 - 28575761
AN - SCOPUS:85019995838
VL - 72
SP - 127
EP - 134
JO - Epilepsy and Behavior
JF - Epilepsy and Behavior
SN - 1525-5050
ER -