Lacosamide as adjunctive therapy for partial‐onset seizures: A randomized controlled trial

Abstract

Methods: This multicenter, double-blind, placebo-controlled trial randomized patients 1:2:1 to placebo, lacosamide 400 mg, or lacosamide 600 mg/day. After an 8-week baseline period, patients began treatment with placebo or lacosamide 100 mg/day, were force-titrated weekly (100 mg/day increments) to the target dose, and entered a 12-week maintenance period. Results: A total of 405 patients were randomized and received trial medication. Most (82.1%) were taking two to three concomitant AEDs. Median percent reductions in seizure frequency per 28 days from baseline to maintenance (intention-to-treat, ITT) were 37.3% for lacosamide 400 mg/day (p = 0.008) and 37.8% for lacosamide 600 mg/day (p = 0.006) compared to 20.8% for placebo, with responder rates of 38.3% and 41.2%, respectively, compared to placebo (18.3%, p < 0.001; ITT). Patients randomized to lacosamide showed large reductions in secondarily generalized tonic-clonic seizures, with median percent reductions in seizure frequency of 59.4% for lacosamide 400 mg/day and 93.0% for lacosamide 600 mg/day compared to 14.3% for placebo, and responder rates of 56.0% and 70.2% compared to placebo (33.3%). Dose-related adverse events included dizziness, nausea, and vomiting. Discussion: Adjunctive treatment with lacosamide 400 and 600 mg/day reduced seizure frequency for patients with uncontrolled partial-onset seizures. Lacosamide 400 mg/day provided a good balance of efficacy and tolerability; lacosamide 600 mg/day may provide additional benefit for some patients as suggested by secondary efficacy analyses, including response in patients with secondarily generalized tonic-clonic seizures.

Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy

“…In the overall population, 14.0% of patients remained seizure‐free during the maintenance phase; among those treated with LCM ≤400 mg/day, the corresponding value was 18.9%. These rates compared favourably with those obtained in the pivotal trials (3.3% and 4.8% for patients treated with LCM 400 and 600 mg/day, respectively) 19. It is important to note, however, that comparisons of the results should be interpreted with caution, given different trial designs.…”

“…In the pivotal trials, patients with highly refractory disease received LCM in a fixed titration scheme added to a variety of AEDs—up to 82% had a SCB in their treatment regimen 9, 19. Post hoc analyses based on the mechanism of action of patients’ concomitant AEDs suggested that LCM therapy resulted in significant seizure reduction relative to placebo, regardless of presence/absence of SCBs 9.…”

Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

“…Lacosamide was approved in Europe in September 2008 for partial-onset seizures in patients 16 years and older [74]. Lacosamide has a bioavailability of ~100% with minimal first-pass metabolism and serum protein binding [75].…”

Antiepileptic Drugs 2012: Recent Advances and Trends

“…[16][17][18][19] Patients had partial-onset seizures with or without secondary generalization that were not adequately controlled with 1 to 3 other AEDs. Patients averaged 4 or more seizures every 28 days and no seizure-free period exceeding more than 21 days.…”

“…[16][17][18][19] Syncope was reported in a trial of lacosamide for diabetic neuropathy, an indication for which it was not approved. A small but measurable dose-dependent PR-interval prolongation has been observed in association with lacosamide; therefore, caution of its use is advised for patients with known cardiac conduction problems.…”