Background: Lacosamide is a functionalized amino acid that has shown activity in a wide-range of animal models for pain and epilepsy.

Methods: In this ongoing, open-label trial, subjects enrolling from one of three preceding trials are titrated to their optimal lacosamide dose (100-600 mg/day) in weekly increments of 100 mg/day prior to entering a long-term maintenance period. Dose adjustments are allowed as necessary. Pain is assessed by twice-daily diary entries using an 11-point Likert scale, and the Patient's Global Impression of Change in Pain (PGIC) is assessed periodically.

Results: As of the interim analysis cut-off, February 10, 2006, 451 subjects received lacosamide in this trial; 314 (69.6%) subjects were ongoing. Twelve subjects (2.7%) discontinued due to lack of efficacy. The mean number of days of exposure was 216 and the maximum duration of lacosamide exposure was 516. The most common doses were 400 mg/day (26.4% of subjects) and 600 mg/day (22.0% of subjects). The mean Likert pain score at Baseline was 6.35. The mean Likert pain score at the end of titration and after 6, 12, and 18 months in the maintenance phase was 2.78, 2.16, 2.33, and 2.28, respectively. After 6-months in the maintenance phase, 96.2% of subjects reported feeling better (PGIC response of much better, moderately better, mildly better) versus 3.8% reporting either no change or worse. The proportion of subjects reporting feeling better at 12- and 18-months in maintenance was 95.8% and 96.4%, respectively.

Adverse events (AEs) were the primary reason for premature discontinuation (12.4% of subjects). The most frequently reported AEs in long-term use included dizziness (19.5%), upper respiratory infection (11.1%), nausea (9.8%), and headache (8.6%).

Conclusion: These data support the continued development of lacosamide in painful diabetic neuropathy.