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

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 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. 633 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 versus 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 versus 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.
Source: Journal of the Peripheral Nervous System - Category: Neurology Authors: Tags: RESEARCH REPORTS Source Type: research