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 fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy.


METHODS
A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms.


RESULTS
Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, 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 electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including 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 versus placebo group at the study conclusion. At the dose used, fidarestat was 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 the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy.
Hotta
N
N
Third Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan. hotta@chubuh.rofuku.go.jp
Toyota
T
T
Matsuoka
K
K
Shigeta
Y
Y
Kikkawa
R
R
Kaneko
T
T
Takahashi
A
A
Sugimura
K
K
Koike
Y
Y
Ishii
J
J
Sakamoto
N
N
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006987:Hypesthesia; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D048289:Imidazolidines; D008297:Male; D008875:Middle Aged; D010146:Pain; D010292:Paresthesia; D010919:Placebos
D000449:Aldehyde Reductase; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D007093:Imidazoles; D048289:Imidazolidines; D010919:Placebos; C077139:fidarestat