Background: Lacosamide (SPM 927, R-2-acetamido-N-benzyl-3-methoxypropionamide) is a functionalized amino acid that has shown activity in a wide range of animal models for pain and epilepsy.

Design/Methods: Four hundred sixty-nine (469) patients were randomized (1:2:2:2) to placebo (n=66), 200 (n=141), 400 (n=125), or 600 mg/day (n=137) lacosamide treatment arms. Subjects titrated to their assigned dose then entered a 12-week maintenance phase. No dose adjustments were allowed. Subjects rated their pain twice daily using an 11-point Likert scale. Adverse events were assessed throughout the trial.

Results: Mean reduction in pain scores from baseline to the last 4 weeks of maintenance were -1.67, -2.01, -2.29, and -2.23 in the placebo, 200, 400, and 600 mg/day lacosamide arms, respectively, and approached significance (P=.0507) for the 400 mg/day lacosamide arm. A statistically significant separation between 400 and 600 mg/day lacosamide treatment and placebo arms was achieved early during titration and was also observed for the entire titration and maintenance period. Most AEs were mild or moderate in intensity and had their onset during the titration phase. The incidence rates of AEs were similar across all treatment arms. The rate of early discontinuations was 31.8%, 32.6%, 43.2%, and 66.4% in the placebo, 200, 400, and 600 mg/day lacosamide arms, respectively. The most frequently reported AEs were dizziness, nausea, balance disorder, tremor, and headache.

Conclusions: Lacosamide at doses of 400 mg/day and 600 mg/day significantly reduced pain scores in subjects with diabetic neuropathy during titration and the entire 12-week maintenance period of this trial. The 200 mg/day and 400 mg/day lacosamide doses were better tolerated than the 600 mg/day dose in this trial.