[Source: Docguide.com, Andrew N. Wilner, MD, FACP, FAA] – Lacosamide is more effective than placebo in decreasing seizure frequency in patients with uncontrolled partial-onset epileptic seizures, according to results of a phase 3 trial presented here at the American Neurological Association (ANA) 133rd Annual Meeting.
These results reinforce the findings of 2 previous trials of lacosamide (SP667 and SP755) for epilepsy control, so said the investigators, led by Steve Chung, MD, Barrow Neurological Institute, Phoenix, Arizona. Lacosamide is an investigational drug pending approval by the US Food and Drug Administration for partial-onset seizures and diabetic neuropathic pain, the researchers noted at a poster presentation on September 22.
In this placebo-controlled clinical trial (SP754) of 405 patients, subjects were randomised 1:2:1 to either placebo, lacosamide 400 mg/day, or lacosamide 600 mg/day (twice-daily administration).
At baseline, all subjects were taking 1 to 3 other antiepileptic drugs, which included levetiracetam, lamotrigine, carbamazepine, oxcarbazepine, phenytoin, topiramate, valproate, and zonisamide. The trial had an 8-week baseline phase, a 6-week titration phase, and a 12-week maintenance phase.
The median percentages of seizure reductions were as follows: 21% in the group on placebo (n = 104), 37% in the group receiving lacosamide 400 mg/day (n = 201) (P = .0078), and 38% in the group on lacosamide 600 mg BID (n = 97) (P = .0061). The 50% response rate was 18% in the placebo group, 38% in the group receiving lacosamide 400 mg/day (P = .0084), and 41% in the group on lacosamide 600 mg BID (P = .0005).
In addition, patients taking both doses of lacosamide had a significant increase in the number of seizure-free days: 5.25 days for 400 mg/day (P = .013) and 8.22 days for 600 mg BID (P < .001). Nine patients taking lacosamide achieved freedom from seizures throughout the entire maintenance phase, compared with none of the patients on placebo.
The most common adverse events affected the central nervous and gastrointestinal tract (dizziness, nausea, diplopia, blurred vision). Adverse events were mild to moderate and were most common during the titration phase. A dose-related increase in the PR interval on electrocardiography (EKG) was observed as follows: placebo (1.2 ms), lacosamide 400 mg/day (4.4 ms), and lacosamide 600 mg BID (6.1 ms). No clinically significant changes on EKG, laboratory values, vital signs, or weight were observed.
Withdrawal from the study due to adverse events occurred in 5% of the group on placebo, 18% of the group on lacosamide 400 mg/day, and 27% of the group on lacosamide 600 mg BID. Adverse events most likely to result in study withdrawal were dizziness and decreased coordination.
The mean age of subjects in this study was 38.3 years, with a mean epilepsy duration of 24.5 years.
Funding for this study was supported by UCB Pharma, Inc