Efficacy and safety of lacosamide in diabetic neuropathic pain: an 18-week double-blind placebo-controlled trial of fixed-dose regimens.
OBJECTIVE
The aims of this multicenter, randomized, placebo-controlled, double-blind trial were to confirm the efficacy of lacosamide at a daily dose of 400 mg/d and to explore the efficacy, safety, and tolerability of lacosamide 200 mg/d and 600 mg/d in the treatment of painful diabetic neuropathy.


METHODS
The trial consisted of a 2-week run-in period, a 6-week titration phase, and a 12-week maintenance phase, during which patients received placebo or fixed doses of lacosamide 200, 400, or 600 mg/d. No back titration was allowed during the trial. The primary efficacy criterion was the change in Likert pain score from baseline to the average over the last 4 weeks of the maintenance phase in the intent-to-treat population.


RESULTS
The lacosamide 400 mg/d group demonstrated statistically significant improvement in Likert pain score over placebo for the primary efficacy measure. At the end of treatment, 58% of patients in the lacosamide 400 mg/d treatment group achieved at least a 2-point or 30% reduction in Likert pain score, compared with 46% of placebo-treated patients. The lacosamide 200 mg/d group separated from placebo, but failed to show statistical significance for any of the primary or secondary outcome measures. The lacosamide 600 mg/d group was significantly more efficacious than placebo in the observed cases but not in the intent-to-treat population. This was probably secondary to a relatively high-premature withdrawal rate due to adverse events that occurred during the titration phase in that group. Overall lacosamide at daily doses of 200 to 400 mg was well tolerated, with 8% of patients discontinuing due to an adverse event from the 200 mg/d group and 23% from the 400 mg/d group compared with 9% in the placebo group. Discontinuations due to adverse events were highest in the 600 mg/d group (40%). The most common adverse events consisted of dizziness, nausea, tremor, headache, and fatigue. Somnolence, cognitive and behavioral side effects, weight change, and edema were notably low.


CONCLUSIONS
Safety and efficacy analyses indicated that lacosamide 400 mg/d provided an optimal balance between efficacy and side effects in patients with painful diabetic neuropathy.
Wymer
James P
JP
Upstate Clinical Research, Albany, NY 12205, USA. jwymer@upstateneurology.com
Simpson
Jeffrey
J
Sen
David
D
Bongardt
Sabine
S
D000081:Acetamides / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000008:administration & dosage; D015897:Comorbidity; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000453:epidemiology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D005356:Fibromyalgia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D015990:Placebo Effect; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D000081:Acetamides; D000700:Analgesics; D018765:Dopamine Uptake Inhibitors; D000078334:Lacosamide