TY - JOUR
T1 - Influence of titration schedule and maintenance dose on the tolerability of adjunctive eslicarbazepine acetate
T2 - An integrated analysis of three randomized placebo-controlled trials
AU - Krauss, Gregory
AU - Biton, Victor
AU - Harvey, Jay H.
AU - Elger, Christian
AU - Trinka, Eugen
AU - Soares da Silva, Patrício
AU - Gama, Helena
AU - Cheng, Hailong
AU - Grinnell, Todd
AU - Blum, David
N1 - Funding Information:
G. Krauss has received research support from Sunovion Pharmaceuticals Inc ., Eisai, Upsher-Smith, UCB Pharma, and SK Life Science; and acted as a paid consultant for Otsuka Pharmaceutical. V. Biton has acted as a paid consultant for Merck, Pfizer, Jazz, Upsher-Smith, Lundbeck, Eisai, Avigen, GSK, Ortho-McNeil, Icagen, UCB Schwarz, and Valeant. J. H. Harvey has received research support from Sunovion Pharmaceuticals Inc ., UCB Pharma, Pfizer, SK Life Science, Marinus, Acorda, Upsher-Smith, GW, Merck, and Sage; received lecture fees from Sunovion Pharmaceuticals Inc., and UCB Pharma; acted as a paid consultant for Sunovion Pharmaceuticals Inc.; and served as a Speakers Bureau member for Sunovion Pharmaceuticals Inc., and UCB Pharma. C. Elger has received research support from Deutsche Forschungsgemeinschaft; and acted as a paid consultant for BIAL , Desitin, Novartis, Eisai, and UCB Pharma. E. Trinka has received lecture fees from UCB Pharma, Biogen, Gerot-Lannach, BIAL, Eisai, Takeda, Newbridge, and Sunovion Pharmaceuticals Inc., Novartis; acted as a paid consultant for UCB Pharma, Biogen, Gerot-Lannach, BIAL, Eisai, Takeda, Newbridge, Sunovion Pharmaceuticals Inc., and Novartis; and received grants from Biogen, Red Bull, Merck, UCB Pharma, European Union, and FWF Österreichischer Fond zur Wissenschaftsförderung, Bundesministerium für Wissenschaft und Forschung. P. Soares da Silva and H. Gama are paid employees of BIAL–Portela & C a , S.A. H. Cheng, T. Grinnell, and D. Blum are employees of Sunovion Pharmaceuticals Inc.
Funding Information:
The clinical studies were sponsored by Sunovion Pharmaceuticals Inc . and BIAL–Portela & C a , S.A. The sponsors were involved in the design of the studies, in the collection, analysis and interpretation of data, in writing the report, and in the decision to submit this article for publication. The authors acknowledge the contributions of Dr Rui Sousa, formerly of BIAL–Portela & Ca, S.A, during development of this article. Medical writing support was funded by Sunovion Pharmaceuticals Inc ., and was provided by Michael Simpson, PhD, CMPP of FireKite, an Ashfield company, part of UDG Healthcare plc.
PY - 2018/1
Y1 - 2018/1
N2 - Objective To examine the influence of titration schedule and maintenance dose on the incidence and type of treatment-emergent adverse events (TEAEs) associated with adjunctive eslicarbazepine acetate (ESL). Methods Data from three randomized, double-blind, placebo-controlled trials were analyzed. Patients with refractory partial-onset seizures were randomized to maintenance doses of ESL 400, 800, or 1200 mg QD (dosing was initiated at 400 or 800 mg QD) or placebo. The incidence of TEAEs was analyzed during the double-blind period (2‐week titration phase; 12-week maintenance phase), according to the randomized maintenance dose and the titration schedule. Results 1447 patients were included in the analysis. During the first week of treatment, 62% of patients taking ESL 800 mg QD had ≥1 TEAE, vs 35% of those taking 400 mg QD and 32% of the placebo group; dizziness, somnolence, nausea, and headache were numerically more frequent in patients taking ESL 800 mg than those taking ESL 400 mg QD. During the double-blind period, the incidences of common TEAEs were lower in patients who initiated ESL at 400 mg vs 800 mg QD. For the 800 and 1200 mg QD maintenance doses, rates of TEAEs leading to discontinuation were lower in patients who began treatment with 400 mg than in those who began taking ESL 800 mg QD. Conclusions Initiation of ESL at 800 mg QD is feasible. However, initiating treatment with ESL 400 mg QD for 1 or 2 weeks is recommended, being associated with a lower incidence of TEAEs, and related discontinuations. For some patients, treatment may be initiated at 800 mg QD, if the need for more immediate seizure reduction outweighs concerns about increased risk of adverse reactions during initiation.
AB - Objective To examine the influence of titration schedule and maintenance dose on the incidence and type of treatment-emergent adverse events (TEAEs) associated with adjunctive eslicarbazepine acetate (ESL). Methods Data from three randomized, double-blind, placebo-controlled trials were analyzed. Patients with refractory partial-onset seizures were randomized to maintenance doses of ESL 400, 800, or 1200 mg QD (dosing was initiated at 400 or 800 mg QD) or placebo. The incidence of TEAEs was analyzed during the double-blind period (2‐week titration phase; 12-week maintenance phase), according to the randomized maintenance dose and the titration schedule. Results 1447 patients were included in the analysis. During the first week of treatment, 62% of patients taking ESL 800 mg QD had ≥1 TEAE, vs 35% of those taking 400 mg QD and 32% of the placebo group; dizziness, somnolence, nausea, and headache were numerically more frequent in patients taking ESL 800 mg than those taking ESL 400 mg QD. During the double-blind period, the incidences of common TEAEs were lower in patients who initiated ESL at 400 mg vs 800 mg QD. For the 800 and 1200 mg QD maintenance doses, rates of TEAEs leading to discontinuation were lower in patients who began treatment with 400 mg than in those who began taking ESL 800 mg QD. Conclusions Initiation of ESL at 800 mg QD is feasible. However, initiating treatment with ESL 400 mg QD for 1 or 2 weeks is recommended, being associated with a lower incidence of TEAEs, and related discontinuations. For some patients, treatment may be initiated at 800 mg QD, if the need for more immediate seizure reduction outweighs concerns about increased risk of adverse reactions during initiation.
KW - Eslicarbazepine acetate
KW - Partial-onset seizures
KW - Titration schedule
KW - Tolerability
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U2 - 10.1016/j.eplepsyres.2017.10.021
DO - 10.1016/j.eplepsyres.2017.10.021
M3 - Article
C2 - 29127848
AN - SCOPUS:85032967495
VL - 139
SP - 1
EP - 8
JO - Epilepsy Research
JF - Epilepsy Research
SN - 0920-1211
ER -