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Clinical Trial
. 2019 Dec;60(12):2437-2447.
doi: 10.1111/epi.16381. Epub 2019 Nov 21.

Long-term safety and efficacy of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed epilepsy

Elinor Ben-Menachem  1 , Hans Peter Grebe  2 , Kiyohito Terada  3 , Lori Jensen  4 , Ting Li  4 , Marc De Backer  5 , Björn Steiniger-Brach  5 , Teresa Gasalla  4 , Melissa Brock  4 , Victor Biton  6
Affiliations
Clinical Trial

Long-term safety and efficacy of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed epilepsy

Elinor Ben-Menachem et al. Epilepsia. 2019 Dec.

Erratum in

  • Corrigendum.
    [No authors listed] [No authors listed] Epilepsia. 2021 Apr;62(4):1039. doi: 10.1111/epi.16767. Epub 2020 Nov 25. Epilepsia. 2021. PMID: 33836101 Free PMC article. No abstract available.

Abstract

Objective: A large-scale, double-blind trial (SP0993; NCT01243177) demonstrated that lacosamide was noninferior to controlled-release carbamazepine (carbamazepine-CR) in terms of efficacy, and well tolerated as first-line monotherapy in patients (≥16 years of age) with newly diagnosed epilepsy. We report primary safety outcomes from the double-blind extension of the noninferiority trial (SP0994; NCT01465997) and post hoc analyses of pooled long-term safety and efficacy data from both trials.

Methods: Patients were randomized 1:1 to lacosamide or carbamazepine-CR. Doses were escalated (lacosamide: 200/400/600 mg/d; carbamazepine-CR: 400/800/1200 mg/d) based on seizure control. Eligible patients continued randomized treatment in the extension. Primary outcomes of the extension were treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs. Post hoc analyses of data from combined trials included 12- and 24-month seizure freedom and TEAEs by number of comorbid conditions.

Results: A total of 886 patients were treated in the initial trial and 548 in the extension; 211 of 279 patients (75.6%) on lacosamide and 180/269 (66.9%) on carbamazepine-CR completed the extension. In the extension, 181 patients (64.9%) on lacosamide and 182 (67.7%) on carbamazepine-CR reported TEAEs; in both groups, nasopharyngitis, headache, and dizziness were most common. Serious TEAEs were reported by 32 patients (11.5%) on lacosamide and 22 (8.2%) on carbamazepine-CR; 12 (4.3%) and 21 (7.8%) discontinued due to TEAEs. In the combined trials (median exposure: lacosamide 630 days; carbamazepine-CR 589 days), Kaplan-Meier estimated proportions of patients with 12- and 24-month seizure freedom from first dose were 50.8% (95% confidence interval 46.2%-55.4%) and 47.0% (42.2%-51.7%) on lacosamide, and 54.9% (50.3%-59.6%) and 50.9% (46.0%-55.7%) on carbamazepine-CR. Incidences of drug-related TEAEs and discontinuations due to TEAEs increased by number of comorbid conditions and were lower in patients on lacosamide.

Significance: Long-term (median ~2 years) lacosamide monotherapy was efficacious and generally well tolerated in adults with newly diagnosed epilepsy. Seizure freedom rates were similar with lacosamide and carbamazepine-CR.

Keywords: antiepileptic drug; comorbidity; lacosamide monotherapy; tolerability.

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Conflict of interest statement

Elinor Ben‐Menachem has served as a paid consultant for Eisai, Sandoz, and UCB Pharma; has received research grants from Eisai, GW Pharmaceuticals, SK Life Science, and UCB Pharma; and is the Editor‐in‐Chief of Acta Neurologica Scandinavica. Hans‐Peter Grebe received advisory board honoraria from Eisai. Kiyohito Terada has received speaker's fees from Daiichi‐Sankyo, Eisai, Otsuka Pharmaceutical, and UCB Pharma. Lori Jensen, Ting Li, Marc De Backer, Björn Steiniger‐Brach, Teresa Gasalla, and Melissa Brock are employees of UCB Pharma. Victor Biton has served as a paid consultant for Avigen, Eisai, GlaxoSmithKline, Icagen, Jazz Pharmaceuticals, Lundbeck, Merck, Ortho‐McNeil, Pfizer, UCB Pharma, Upsher‐Smith Laboratories, and Valeant Pharmaceuticals. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Figures

Figure 1
Figure 1
Patient disposition in the combined trials until unblinding. FAS, full analysis set; SS, safety set. a548 patients were treated in the extension trial (lacosamide, 279 patients; carbamazepine‐CR, 269 patients)
Figure 2
Figure 2
Time to discontinuation due to lack of efficacy or adverse event (A), due to adverse event (B), or due to lack of efficacy (C) during the combined double‐blind period (FAS). CBZ‐CR, controlled‐release carbamazepine; FAS, full analysis set; LCM, lacosamide
Figure 3
Figure 3
Patients with at least one 6‐ and 12‐mo seizure‐free interval up to unblinding (FAS). Lacosamide: dose level 1, 200 mg/d; dose level 2, 400 mg/d; dose level 3, 600 mg/d; carbamazepine‐CR: dose level 1, 400 mg/d; dose level 2, 800 mg/d; dose level 3, 1200 mg/d. FAS, full analysis set
See this image and copyright information in PMC

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