12-Month Efficacy and Safety of Diepalrestat in Adults With Diabetic Peripheral Neuropathy, a DB, Placebo-Controlled Study (DE-DPN)

Twelve-Month Chronic Efficacy and Safety of Diepalrestat in Adult Subjects With Diabetic Peripheral Neuropathy (DPN), A Randomized, Double-Blind, Placebo-Controlled Study

An interventional study to investigate the efficacy and safety of diepalrestat (BNV-222) in diabetic patients with diabetic peripheral neuropathy. Subjects will receive twice daily an oral dose of diepalrestat, an aldose reductase inhibitor, or placebo to investigate the effect on motor nerve conduction velocity (MNCV) and symptomatic clinical responses over 12 months of treatment. Subjects will be assessed at screening and baseline, with office visits every 12 weeks, for a total of 6 visits. The study will explore in a double-blind fashion, the effect of two doses of diepalrestat, 150 and 300 mg, to reduce the loss in nerve conduction velocity that is expected to be demonstrated in the group randomized to placebo treatment for up to 12 months.

Study Overview

• Status: Completed
• Conditions: Diabetic Peripheral Neuropathy
• Intervention / Treatment: Drug: Placebo; Drug: diepalrestat choline

Detailed Description

This 12 month double-blind, randomized, placebo-controlled, parallel group efficacy and safety study will enroll 400 adult diabetic subjects with diabetic peripheral neuropathy (DPN) to investigate the effect of diepalrestat (BNV-222) 150 mg, 300 mg, or placebo on MNCV and patients' perception of nerve function over 12 months as measured by VAS scales and composite clinical outcome patient reported scales that evaluate numbness, tingling, cramping, paresthesiae, hyperesthesia, coldness, weakness and spontaneous pain perception of upper and lower extremities, and the effects on other measures of nerve motor and sensory conduction. Subjects will be assessed at screening and baseline, with office visits every 12 weeks, for a total of 6 visits. Subjects will be assessed by testing motor nerve conduction velocity and other assessments at each office visit. A subgroup of 24 patients will be selected for pharmacokinetic (PK) testing for up to 48 hours with additional blood draws on Day 7 and 14. This study will investigate the ability of diepalrestat to reduce the ongoing deterioration of nerve function which is a hallmark of the DPN process.

• Study Type: Interventional
• Enrollment (Actual): 330
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Arkhangelsk, Russian Federation, 163000
    • Northern State Medical University
  • Cherepovets, Russian Federation, 162600
    • Health Services Severstal
  • Ekaterinburg, Russian Federation, 620014
    • Clinic of Neurology
  • Kemerovo, Russian Federation, 650066
    • Kemerovo Regional Clinical Hospital
  • Moscow, Russian Federation, 119034
    • Endocrinology Dispensary
  • Moscow, Russian Federation, 119049
    • Morozovskaya Children City Hospital of Moscow
  • Moscow, Russian Federation, 119435
    • I M Sechenov First Moscow State Medical University
  • Moscow, Russian Federation, 119435
    • IM Sechenov First Moscow State Medical University
  • Moscow, Russian Federation, 119991
    • IM Sechenov First Moscow State Medical University
  • Moscow, Russian Federation, 121374
    • City Clinical Hospital No 71
  • Moscow, Russian Federation, 125367
    • Central Clinical Hospital No 1 of JSC Russian Railway
  • Moscow, Russian Federation, 127206
    • City Clinical Hospital No 50
  • Moscow, Russian Federation, 127486
    • The Federal Bureau of Medical and Social Expertise
  • Perm, Russian Federation, 614107
    • Perm State Medical Academy
  • Petrozavodsk, Russian Federation, 185019
    • VA Baranov Respublical Hospital
  • Rostov-on-Don, Russian Federation, 344022
    • Rostov State Medical University
  • Saratov, Russian Federation, 410053
    • City Polyclinic No 20
  • St Petersburg, Russian Federation, 191186
    • Imc Sogaz
  • St Petersburg, Russian Federation, 194295
    • Medical Center Reavita
  • St Petersburg, Russian Federation, 195257
    • City Hospital of the Holy Martyr Elizabeth
  • St Petersburg, Russian Federation, 198510
    • Nikolaev Hospital
  • Ufa, Russian Federation, 450000
    • Bashkir State Medical University
  • Ulyanovsk, Russian Federation, 432057
    • Central City Clinical Hospital
  • Volgograd, Russian Federation, 400131
    • State Medical University
  • Yaroslavl, Russian Federation, 150000
    • Regional Clinical Hospital
  • Yaroslavl, Russian Federation, 150003
    • NV Solovyov Clinical Emergency Hospital
  • Sestroretsk
    • St Petersburg, Sestroretsk, Russian Federation, 197706
      • City Hospital No 40 of the Kurortny District

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with type 1 or type 2 diabetes mellitus that is controlled by oral or parenteral hypoglycemic agents or diet.
• Patients with diabetes that is stable and controlled (HbA1C ≤ than 10 %) with no new symptoms associated with diabetes within previous 3 months.
• Patients diagnosed with neuropathy who have abnormalities in 2 of 3 categories (signs, symptoms, and objective tests of nerve conduction studies or quantitative sensory threshold testing).
• Patients on pain medication (prescribed analgesics), stable for at least 3 months before study entry or pain treatment naive.
• Patients with at least mild painful symptoms of diabetic neuropathy for at least 1 year duration, but not longer than 10 years duration.
• Able to withstand the fundus evaluation during ophthalmology testing

Exclusion Criteria:

• A condition that would preclude a patient for participation in the study in opinion of investigator, e.g., unstable medical status including glycemic control and blood pressure.
• Any neurological disorder that may confound assessment of diabetic peripheral neuropathy such as radiculopathies. multiple sclerosis, myelopathies.
• Ongoing severe peripheral arterial diseases, skin ulcers, or amputation in the lower extremities.
• Neuropathy findings due to any of the following: alcohol abuse, liver or renal disease, toxic exposure, endocrine, metabolic or nutritional disorders, inflammatory diseases, or monoclonal gammopathies.
• Patients with absent peroneal nerve response.
• Other pain that may confound assessment of neuropathic pain.
• Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1 150 mg; 150 mg diepalrestat choline administered as twice daily dosing morning and evening with an oral tablet of either 150 mg diepalrestat choline or placebo	Drug: diepalrestat choline; aldose reductase inhibitor; Other Names: BNV-222
Active Comparator: Group 2 300 mg; 300 mg diepalrestat choline administered as twice daily dosing morning and evening with an oral tablet of 150 mg diepalrestat choline	Drug: diepalrestat choline; aldose reductase inhibitor; Other Names: BNV-222
Placebo Comparator: Group 3; Tablet administered twice daily morning and evening containing placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change from baseline in peroneal motor nerve conduction velocity	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline in patient-reported Visual Acuity Scales	Patients' perception of pain, numbness, tingling, weakness of the foot, ataxia, upper limb symptoms and sensory symptoms assessed by pinprick, light touch, vibration, and temperature	12 months
change from baseline in patient-reported responses to Toronto Clinical Neuropathy Score (TCNS)	TCNS component measures of symptomatic changes in pain, numbness and other measures	12 months
change from baseline in quality of life administered by SF-36 instrument	patient global impression of quality of life assessed by the SF-36 short form	12 months
change from baseline in median conduction velocity measurements	conduction velocity measures including median MNCV,	12 months
change in visual acuity compared to baseline	Change in visual acuity over 12 months compared to baseline, change in diabetic retinopathy in the dilated eye	12 months
change from baseline in MFWL conduction velocity measurement	change from baseline in median F wave latency (MFWL)	12 months
change from baseline in VPT conduction velocity measurement	change from baseline in Vibration Perception Threshold (VPT)	12 months

Collaborators and Investigators

• Sponsor: NeuromaxBionevia
• Investigators: Study Director: Julia Mockot, MD, NeuroMax Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: January 2, 2015
• First Submitted That Met QC Criteria: January 2, 2015
• First Posted (Estimate): January 6, 2015

Study Record Updates

• Last Update Posted (Actual): September 27, 2018
• Last Update Submitted That Met QC Criteria: September 26, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Diabetic Neuropathies; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Nootropic Agents; Lipotropic Agents; Choline
• Other Study ID Numbers: NM-ARI-231

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes