Analysis of Changes in Plasma Sodium Levels and Related Treatment-Emergent Adverse Events During Short- and Long-Term Use of Eslicarbazepine Acetate as Adjunctive and Monotherapy (P4.105)

Objective: To investigate the effect of eslicarbazepine acetate (ESL) on plasma sodium levels and incidence of hyponatremia-related treatment-emergent adverse events (TEAEs). Background: ESL is a once-daily oral antiepileptic drug (AED) for the treatment of partial-onset seizures (POS). ESL is a member of the dibenzazepine carboxamide class of putative voltage-gated sodium channel blockers, use of which has been associated with hyponatremia. Design/Methods: Plasma sodium levels and TEAEs were assessed during Phase III trials of ESL for treatment-refractory POS: three 14-week trials (2093-301, -302, -304) of double-blind adjunctive ESL or placebo (both taken with baseline AEDs); two dose-blind, 18-week conversion-to-monotherapy trials (093-045, -046); and open-label extensions (OLEs; studies 301/302, and 045/046 [093-050]) which allowed flexible dosing. Results: The controlled analysis population comprised 1812 patients; 913 continued into the OLEs. Clinically meaningful minimum post-dose sodium levels (≤125 mEq/L) were reported for 11 (1.1%) patients taking adjunctive ESL and 12 (3.3%) taking ESL monotherapy in the controlled trials, and for 17 (1.9%) patients in the uncontrolled OLEs. Plasma sodium levels decreased by u003e10 mEq/L between baseline and end of study for Conclusions: Reductions in sodium levels and hyponatremia-related TEAEs were reported for some patients taking ESL. Monitoring of plasma sodium levels should therefore be considered during ESL treatment, particularly for patients with symptoms of hyponatremia, or for those receiving other medications known to reduce plasma sodium. Study Supported by: Sunovion Pharmaceuticals Inc. Disclosure: Dr. Wechsler has received personal compensation for activities with Cyberonics, Eisai, Sunovion, Marinus, and Lundbeck. Dr. Radtke has received personal compensation for activities with Eisai, Lundbeck, Zynerba, and Sunovion as a scientific advisory board member. Dr. Laxer has received personal compensation for activities with UCB Pharma, Lundbeck, Sunovion, and Livanova for speaking and advisory board. Dr. Trinka has received personal compensation for activities Eisai, Ever Neuropharma, Novartis, Biogen Idec, Medtronics, Bial, GL Pharma, GlaxoSmithKline, Boehringer, Suniovion, Actavis, UCB, Gerrot-Lannach, BIAL, and Takeda. Dr. Trinka has received research support from Biogen, Merchk, UCD, European Union, FWF osterreichischer Fond with Wissenschaftsfoderung, bundesministerium for Wissenschaft and Forschung. Dr. Vieira has received personal compensation for activities with Bial-Portela. Dr. Moreira has received personal compensation for activities with BIAL as an employee. Dr. Rocha has received personal compensation for activities with Bial - Portela u0026 Ca as an employee. Dr. Rocha has received research support from Eisai, Marinus, Pfizer, Sunovion, and UCB Dr. Cheng has received personal compensation for activities with Sunovian Pharmaceuticals, Inc. as an employee. Dr. Grinnell has received personal compensation for activities with Sunovion Pharmaceuticals as an employee. Dr. Blum has received personal compensation for activities with Sunovion Pharmaceuticals Inc. as an employee.