Anticonvulsant lacosamide exhibits pain reduction in phase 3 diabetic neuropathy trial

The anticonvulsant lacosamide is effective in relieving diabetic neuropathy and produces increased pain reduction with continued treatment for 22 months, according to phase 3 study results presented during the 25th Annual Scientific Meeting of APS in San Antonio, Texas. "This is a promising treatment that maintains a long-term effect," said Tibor Hidvegi, MD, Medical Department, Petz Hospital, Gyor, Hungary.

The trial included 469 distal diabetic neuropathy patients with pain scores of ≥4 on the 11-point Likert Scale at baseline. They were randomized to receive 200 mg, 400 mg, or 600 mg lacosamide daily or placebo for 18 weeks.

Statistically significant reductions in pain score were seen after 2 weeks of treatment in the 600-mg lacosamide group versus placebo, and at Week 18 there was a 2.5-point reduction in pain score (P=.0065). Pain reduction was observed by the fourth week of treatment among patients receiving 400 mg lacosamide with a similar point reduction in pain score at Week 18 (P=.0069).

In an open-label follow-on trial, 214 patients who had been titrated to their optimal lacosamide dose during a double-blind trial continued treatment. This trial is ongoing, and 22-month results were presented. The average lacosamide dose was 400 mg daily, and the median duration of treatment was 358 days. Pain score reduction occurred most rapidly during the first 2 months of treatment with a mean 2-point reduction occurring during the double-blind phase and an additional 1.25-point reduction occurring during the first 4 weeks of open-label treatment. At 22 months, there was a mean reduction of 4 points on the Likert Scale.

Patients also experienced a 3.2-point reduction in their perception of pain interference with sleep, a 3.1-point reduction in pain interference with activity, and a 3- to 7-point reduction in overall pain using the Visual Analog Scale when treated with lacosamide.

Adverse events were reported by 83% of patients, with 18% reporting an adverse event of severe intensity. Twenty-four patients (11%) discontinued treatment due to adverse events. Adverse events likely to be treatment-related were dizziness in 12% of patients, vertigo in 9%, headache in 8%, and tremor in 6%. The investigators found no prolonged QTc intervals among patients taking lacosamide, and there were no clinically relevant effects on laboratory parameters during the 22 months of treatment.

In clinical trials conducted in healthy patients and in phase 2 clinical trials in patients with epilepsy, researchers reported that lacosamide does not interact with oral contraceptive agents and does not influence the rate and extent of absorption of valproic acid, carbamazepine, digoxin, or metformin.