Evaluating the Efficacy and Safety of Oral Ranirestat (40 and 80 mg) in Mild to Moderate Diabetic Sensorimotor Polyneuropathy

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of 40 mg and 80 mg ranirestat on peroneal motor nerve conduction velocity relative to placebo in subjects with mild to moderate diabetic sensorimotor polyneuropathy.

Official Title
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A 2-year, Randomized, Double-blind, Placebo-controlled, Multi-center, Phase II-III Study to Evaluate the Efficacy and Safety of Oral Ranirestat (40 and 80 mg) in Mild to Moderate Diabetic Sensorimotor Polyneuropathy

Conditions
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Mild to Moderate Diabetic Sensorimotor Polyneuropathy

Intervention / Treatment
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* Drug: Ranirestat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with Type 1 or Type 2, insulin-dependent or non insulin-dependent diabetes mellitus. Subjects with a history of distal symmetric polyneuropathy, secondary to diabetes, diagnosed in accordance with the American Academy of Neurology criteria. Female subjects, who are of non-reproductive potential (>=12 months post-menopausal or surgically sterile) or who are using adequate contraception which includes abstinence or double barrier methods (diaphragm and condom with spermicidal cream, intrauterine device and condom with spermicidal cream). Male subjects with partners of child-bearing potential must also use adequate contraception. Subjects must be able to read, understand, and provide written informed consent before enrolling in the study at screening. Exclusion Criteria: History of diabetic foot ulcers or lower extremity amputation. Diabetic amyotrophy or non-diabetic cause of lower limb neuropathy/neuropathic symptoms. Clinically significant illness which, in the opinion of the investigator, would compromise a subject's suitability to participate in the study for reasons of safety or would confound the efficacy assessments.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranirestat 80 mg<br>Two 80 mg Ranirestat tablets, given orally, once daily, preferably in the morning with or without a light breakfast, for upto 24 months. | Drug: Ranirestat<br>* Ranirestat 40 mg tablets<br>|
| Experimental: Ranirestat 40 mg<br>One 40 mg tablet of Ranirestat and a matching placebo, given orally, once daily, preferably in the morning with or without a light breakfast, for upto 24 months. | Drug: Ranirestat<br>* Ranirestat 40 mg tablets<br>Drug: Placebo<br>* Placebo tablets<br>|
| Placebo Comparator: Placebo<br>Two placebo tablets, given orally, once daily, preferably in the morning with or without a light breakfast, for upto 24 months. | Drug: Placebo<br>* Placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peroneal motor nerve conduction velocity: the mean of duplicate bilateral recordings made within 1-21 days of each other. |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathy total symptom score-6 via a self-administered questionnaire and vibration perception threshold recorded with a neurothesiometer. |  | 24 months |