Long-term efficacy of Lacosamide in subjects with painful distal diabetic neuropathy

Lacosamide (LCM), an anticonvulsant with a dual mode of action, is being investigated for its potential effect in reducing painful diabetic neuropathy (PDN). In a double-blind trial, 106 subjects on open-label, long-term treatment [median (range) = 612 (490-785) days] with 100-400 mg/day lacosamide were randomized to have lacosamide abruptly withdrawn and then reintroduced at the same dose at pre-specified time points. The trial consisted of 4 periods °Ü28 days in length. Subjects received sequences of either LCM-placebo-LCM-LCM or LCM-LCM-placebo-LCM. The primary efficacy variable was the change in average daily pain score for each subject, from baseline to the last 7 days of the placebo period compared to the last 7 days of each lacosamide period, using an 11-point pain scale. The primary efficacy variable was analyzed using statistical methods for repeated measures. The primary model for analysis included explanatory variables for period, treatment, pooled investigator type, and baseline pain score. The results showed the difference between placebo and lacosamide treatment in LS Mean pain score was 0.30 points in favor of lacosamide and statistically significant (P=.007). The secondary efficacy variables also consistently indicated increased pain during placebo treatment and improvement of pain upon retreatment with lacosamide. The mean change from baseline to end of the placebo period was 0.65 points on the pain scale and statistically significant (P<.001). The trial revealed no new safety concerns and there were no AEs suggestive of withdrawal effects following abrupt discontinuation of lacosamide. This is the first controlled trial to provide evidence for long-term efficacy (>1 year) of a treatment for PDN. Supported by grants from SCHWARZ BIOSCIENCES GmbH (UCB).