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

Diabetic Peripheral Neuropathy Clinical Trial

— DE-DPN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02332005
• Other study ID #: NM-ARI-231
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: November 2014
• Est. completion date: November 2017

Study information

• Verified date: September 2018
• Source: NeuromaxBionevia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: November 2017
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Diabetic Peripheral Neuropathy
• Peripheral Nervous System Diseases

Intervention

Drug:
• diepalrestat choline
aldose reductase inhibitor
• Placebo
Placebo

Locations

Country	Name	City	State
Russian Federation	Northern State Medical University	Arkhangelsk
Russian Federation	Health Services Severstal	Cherepovets
Russian Federation	Clinic of Neurology	Ekaterinburg
Russian Federation	Kemerovo Regional Clinical Hospital	Kemerovo
Russian Federation	Central Clinical Hospital No 1 of JSC Russian Railway	Moscow
Russian Federation	City Clinical Hospital No 50	Moscow
Russian Federation	City Clinical Hospital No 71	Moscow
Russian Federation	Endocrinology Dispensary	Moscow
Russian Federation	I M Sechenov First Moscow State Medical University	Moscow
Russian Federation	IM Sechenov First Moscow State Medical University	Moscow
Russian Federation	IM Sechenov First Moscow State Medical University	Moscow
Russian Federation	Morozovskaya Children City Hospital of Moscow	Moscow
Russian Federation	The Federal Bureau of Medical and Social Expertise	Moscow
Russian Federation	Perm State Medical Academy	Perm
Russian Federation	VA Baranov Respublical Hospital	Petrozavodsk
Russian Federation	Rostov State Medical University	Rostov-on-Don
Russian Federation	City Polyclinic No 20	Saratov
Russian Federation	City Hospital No 40 of the Kurortny District	St Petersburg	Sestroretsk
Russian Federation	City Hospital of the Holy Martyr Elizabeth	St Petersburg
Russian Federation	Imc Sogaz	St Petersburg
Russian Federation	Medical Center Reavita	St Petersburg
Russian Federation	Nikolaev Hospital	St Petersburg
Russian Federation	Bashkir State Medical University	Ufa
Russian Federation	Central City Clinical Hospital	Ulyanovsk
Russian Federation	State Medical University	Volgograd
Russian Federation	NV Solovyov Clinical Emergency Hospital	Yaroslavl
Russian Federation	Regional Clinical Hospital	Yaroslavl

Sponsors (1)

Lead Sponsor	Collaborator
NeuromaxBionevia

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change from baseline in peroneal motor nerve conduction velocity		12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	change from baseline in median conduction velocity measurements	conduction velocity measures including median MNCV,	12 months
Secondary	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
Secondary	change from baseline in MFWL conduction velocity measurement	change from baseline in median F wave latency (MFWL)	12 months
Secondary	change from baseline in VPT conduction velocity measurement	change from baseline in Vibration Perception Threshold (VPT)	12 months