Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy - A 52-week multicenter placebo-controlled double-blind parallel group study

OBJECTIVE - The purpose of this study was to evaluate the efficacy of fidar estat a novel, aldose reductase (AR) inhibitor, in a double-blind placebo c ontrolled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy. RESEARCH DESIGN AND METHODS - A total of 279 patients with diabetic neuropa thy were treated With placebo or fidarestat at a daily dose of I mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of Median and tibial motor nerve conduction velocity, F-wave m inimum latency, F-wave conduction velocity (FCV), an me an sensory nerve co nduction velocity (forearm and distal), as well as an assessment of. subjec tive Symptoms. RESULTS - Over the course of the study, five of the eight electrophysiologi cal measures assessed showed significant improvement from baseline in the f idarestat-treated group, whereas no measure showed significant deterioratio n. In contrast, in the placebo group, no electrophysiological measure was i mproved, and one measure significantly deteriorated (i.e., median nerve FCV ). At the Study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electro physiological measu res (i.e., median nerve FCV and minimal latency). Subjective symptoms (incl uding numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated ve rsus placebo group at the study conclusion. At the dose used, fidarestat wa s well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group. CONCLUSIONS - The effects of fidarestat-treatment on nerve conduction and t he subjective symptoms of diabetic neuropathy provide evidence that this tr eatment alters the progression of diabetic neuropathy.