A multicenter, double-blind, randomized, placebo-controlled crossover evaluation of a short course of 4030W92 in patients with chronic neuropathic pain

Abstract

Several lines of evidence suggest that neuropathic pain is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons. The purpose of this study was to examine the safety, analgesic efficacy, and tolerability of oral 4030W92 (a new novel sodium channel blocker) in a group of subjects with chronic neuropathic pain. This study used a randomized, double-blind, placebo-controlled, crossover design in 41 subjects with neuropathic pain with a prominent allodynia. Each subject received a 2-week course of 4030W92 (25 mg/day) and placebo separated by a 2-week washout period. At baseline, postdose day 1, day 7, and day 14, the following were measured: (1) spontaneous and evoked pain scores, (2) dynamic and static allodynia mapping, (3) Short Form McGill Pain Questionnaire, and (4) blood sample for 4030W92 assay. At baseline and day 14 the following were measured: (1) thermal testing in the painful area, (2) Medical Outcomes Study Short Form 36 Questionnaire, and (3) patient global satisfaction. Allodynia severity was significantly lower (P =.046) on treatment day 1, postdose for 4030W92 compared to placebo. However, this was not maintained on treatment day 7 or 14. The area of static allodynia was significantly smaller (P =.03) on treatment day 7 for 4030W92 compared to placebo. However, this was not maintained to treatment day 14. There was no significant effect of 4030W92 on any other efficacy measure. Side effects were minimal. 4030W92, at 25 mg/day, produced a nonsignificant reduction in pain without treatment limiting side effects. The maximum analgesic effect of this drug remains unknown. © 2002 by the American Pain Society