Safety and efficacy of ranirestat in patients with mild-to-moderate diabetic sensorimotor polyneuropathy.

Abstract

We examined the efficacy and safety of ranirestat in patients with diabetic sensorimotor polyneuropathy (DSPN). Patients (18-75 years) with stable type 1/2 diabetes mellitus and DSPN were eligible for this global, double-blind, phase II/III study (ClinicalTrials.gov NCT00927914). Patients (n = 800) were randomized 1 : 1 : 1 to placebo, ranirestat 40 mg/day or 80 mg/day (265 : 264 : 271). Change in peroneal motor nerve conduction velocity (PMNCV) from baseline to 24 months was the primary endpoint with a goal improvement vs. placebo ≥1.2 m/s. Other endpoints included symptoms, quality-of-life, and safety. Six hundred thirty-three patients completed the study. The PMNCV difference from placebo was significant at 6, 12, and 18 months in both ranirestat groups, but <1.2 m/s. The mean improvement from baseline at 24 months was +0.49, +0.95, and +0.90 m/s for placebo, ranirestat 40 mg and 80 mg, respectively (NS). The treatment difference vs. placebo reached significance when ranirestat groups were combined in a post hoc analysis (+0.44 m/s; p = 0.0237). There was no effect of ranirestat on safety assessments, secondary or exploratory endpoints vs. placebo. Ranirestat was well tolerated and improved PMNCV, but did not achieve any efficacy endpoints. The absence of PMNCV worsening in the placebo group underscores the challenges of DSPN studies in patients with well-controlled diabetes.

• Authors: Michael Polydefkis, Joseph Arezzo, Marshall Nash, Vera Bril, Aziz Shaibani, Robert J Gordon, Kate L Bradshaw, Roderick W J Junor, Ranirestat Study Group
• Journal: Journal of the peripheral nervous system : JPNS (J Peripher Nerv Syst) Vol. 20 Issue 4 Pg. 363-71 (Dec 2015) ISSN: 1529-8027 [Electronic] United States
• PMID: 26313450 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Peripheral Nerve Society.

Chemical References

• Pyrazines
• Spiro Compounds
• ranirestat

Topics

• Aged
• Diabetic Neuropathies (drug therapy, physiopathology)
• Disease Progression
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Neural Conduction (drug effects, physiology)
• Polyneuropathies (drug therapy, physiopathology)
• Pyrazines (adverse effects, pharmacology, therapeutic use)
• Quality of Life
• Spiro Compounds (adverse effects, pharmacology, therapeutic use)
• Treatment Outcome