Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures.
OBJECTIVE
To evaluate the efficacy and safety of lacosamide when added to 1 or 2 antiepileptic drugs (AEDs) in adults with uncontrolled partial-onset seizures, and assess plasma concentrations of concomitant AEDs to determine any potential for drug interactions.


METHODS
During this multicenter, double-blind, placebo-controlled trial, patients were randomized to placebo or lacosamide 200, 400, or 600 mg/day after an 8-week baseline period. Lacosamide was titrated in weekly increments of 100 mg/day over 6 weeks and maintained for 12 weeks. Results were analyzed on an intention-to-treat basis.


RESULTS
Four hundred eighteen patients were randomized and received trial medication; 312 completed the trial. The median percent reduction in seizure frequency per 28 days was 10%, 26%, 39%, and 40% in the placebo, lacosamide 200, 400, and 600 mg/day treatment groups, respectively. The median percent reduction in seizure frequency over placebo was significant for lacosamide 400 mg/day (p=0.0023) and 600 mg/day (p=0.0084). The 50% responder rates were 22%, 33%, 41%, and 38% for placebo, lacosamide 200, 400, and 600 mg/day, respectively. The 50% responder rate over placebo was significant for lacosamide 400 mg/day (p=0.0038) and 600 mg/day (p=0.0141). Adverse events that appeared dose-related included dizziness, nausea, fatigue, ataxia, vision abnormal, diplopia, and nystagmus. Lacosamide did not affect mean plasma concentrations of concomitantly administered AEDs.


CONCLUSIONS
In this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial-onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED.
Ben-Menachem
Elinor
E
Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. elinor.ben-menachem@neuro.gu.se
Biton
Victor
V
Jatuzis
Dalius
D
Abou-Khalil
Bassel
B
Doty
Pamela
P
Rudd
G David
GD
D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000284:Administration, Oral; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001259:Ataxia / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D000078334:Lacosamide; D009325:Nausea / Q000139:chemically induced; D010919:Placebos; D016896:Treatment Outcome
D000081:Acetamides; D000927:Anticonvulsants; D010919:Placebos; D000078334:Lacosamide