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Safety and efficacy of ranirestat in patients with mild‐to‐moderate diabetic sensorimotor polyneuropathy
Author(s) -
Polydefkis Michael,
Arezzo Joseph,
Nash Marshall,
Bril Vera,
Shaibani Aziz,
Gordon Robert J.,
Bradshaw Kate L.,
Junor Roderick W. J.
Publication year - 2015
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/jns.12138
Subject(s) - placebo , medicine , clinical endpoint , polyneuropathy , diabetic neuropathy , diabetes mellitus , adverse effect , randomized controlled trial , quality of life (healthcare) , post hoc analysis , physical therapy , anesthesia , endocrinology , alternative medicine , nursing , pathology
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.