Abstract | PURPOSE: To evaluate the efficacy and safety of lacosamide (400 and 600 mg/day) as adjunctive treatment in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs). 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.
|
Authors | Steve Chung, Michael R Sperling, Victor Biton, Gregory Krauss, David Hebert, G David Rudd, Pamela Doty, SP754 Study Group |
Journal | Epilepsia
(Epilepsia)
Vol. 51
Issue 6
Pg. 958-67
(Jun 2010)
ISSN: 1528-1167 [Electronic] United States |
PMID | 20132285
(Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Chemical References |
|
Topics |
- Acetamides
(administration & dosage, adverse effects, pharmacokinetics)
- Adolescent
- Adult
- Aged
- Dizziness
(chemically induced)
- Double-Blind Method
- Drug Therapy, Combination
- Epilepsies, Partial
(drug therapy, metabolism, physiopathology)
- Female
- Humans
- Lacosamide
- Male
- Middle Aged
- Seizures
(drug therapy, metabolism, physiopathology)
- Young Adult
|