Ricolinostat in Patients With Painful Diabetic Peripheral Neuropathy

Phase 2

Completed

Conditions: Painful Diabetic Peripheral Neuropathy

Interventions: Drug: Placebo
Drug: ricolinostat

Registration Number: NCT03176472

Lead Sponsor: Regenacy Pharmaceuticals LLC

Brief Summary: This is a randomized, double-blind, 2-arm, parallel group study of up to 274 evaluable patients designed to evaluate the safety and efficacy of the histone deacetylase 6 (HDAC6) inhibitor ricolinostat for painful DPN.

Detailed Description: The study includes an approximately 12 week randomized, double-blind, placebo controlled Treatment period in which patients will receive either ricolinostat or placebo, followed by an approximately 12 week open label Safety Extension period during which all patients will receive ricolinostat 120 mg daily.

Prior to randomization, patients will be enrolled in a baseline Pain Observation period from Day -14 to Day -1, during which the NRS (average and worst pain) will be recorded daily using an electronic daily diary that will be completed by patients to allow patients to familiarize themselves with the pain rating procedures, and to establish a baseline and confirm eligibility to participate. Patients will also initiate daily dosing during this time to evaluate compliance eligibility for participation. A daily diary will be used by the patient to record the pain assessments and rescue medication use. A follow-up phone contact will be conducted at Day -7 to Day -5 to review diary and dosing compliance.

Following the baseline Pain Observation period, patients who meet entry criteria will be randomized in a 1:1 ratio to receive either ricolinostat or placebo. During the 12-week double-blind, placebo-controlled Treatment period, patients will return for assessments in accordance with the schedule of assessments. At the conclusion of the approximately 12 week open label Safety Extension period, patients will enter a Follow-up safety washout and assessment period, which will incorporate 2 visits at approximately 2 and 4 weeks following the final Safety Extension visit, with assessments performed as outlined in the schedule of assessments.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 282

Inclusion Criteria

Type 1 or Type 2 diabetes of at least 6 months with optimized and stable glycemic control during the 3 months prior to Screening
Painful distal symmetric sensorimotor polyneuropathy due to diabetes
Douleur Neuropathique 4 (DN4) score of ≥4
Satisfactory diary data during the 14-day Pain Observation period determined by an algorithm that includes diary compliance, overall level of pain and day-to-day variability in pain

Exclusion Criteria

Pregnant or lactating
Body Mass Index (BMI) >40 kg/m2
Presence of any neuropathy other than DPN and/or significant risk factors for neuropathy other than diabetes
Other pain conditions that could confound the results of this study, or other chronic pain condition(s) that could affect compliance with pain medication restrictions or confound pain assessments
Painful DPN patients who have undergone lower limb amputations, are non-ambulatory, or whose walking is so impaired as to require a walker or other assistance for ambulation
Have met Diagnostic and Statistical Manual of Mental Disorders V (DSM V) criteria for opioid use disorder or alcohol use disorder
Opioid use at a dose of ≥ 30 morphine milligram equivalents on 3 or more days a week during the month prior to Screening
Suicidal ideation/behavior as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
The use of marijuana or cannabidiol (CBD) during the 30 days prior to starting study drug
Chronic use of over-the-counter capsaicin on extremities within 3 months of Screening and/or prescription Qutenza use within 6 months of Screening
Corrected QT interval at Screening using QTcF of ≥450 msec (male) or ≥460 msec (female)
Hemoglobin < 11.5 g/dL (female) or < 13 g/dL (male), total white blood cell count < 2500/mm3, neutrophil count < 1250/mm3, lymphocyte count < 1000/mm3, or platelet count < 100,000/mm3
HIV positive and/or active hepatitis virus (A, B, or C) infection
Current or previous (≤1 month of Screening) enrollment in a clinical trial involving treatment with an investigational product
Any known recent exposure within the 14 days prior to initial Screening to coronavirus disease 2019 (COVID-19) or symptoms of COVID-19 infection or other reason to suspect COVID-19 infection as assessed by the Investigator at the time of initial Screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Placebo, 12 mL of liquid formulation with no active ingredient (i.e., ricolinostat), taken once daily (QD) by mouth
ricolinostat	ricolinostat	Ricolinostat 120 mg, taken once daily (QD) by mouth; each dose in 12 mL liquid formulation (10 mg ricolinostat per mL)

Primary Outcome Measures

Name	Time	Method
Change in Mean Average Pain Intensity (NRS)	Baseline week [Day-7 to Day 1] compared to Final week [12 Weeks]	Difference between mean average pain intensity using the 11-point numerical pain rating scale (NRS) consisting of pain measurement from 0-10 with 10 being the worst pain and 0 being no pain at all.

Secondary Outcome Measures

Name	Time	Method
Change in Non-pain Neuropathic Signs (UENS)	Baseline week [Day-7 to Day 1] compared to Week 12	Change in non-pain neuropathic signs utilizing the Utah Early Neuropathy Score (UENS) which is a physical examination-based scale designed to assess early sensory predominant polyneuropathy. Compared with other scales, the UENS emphasizes severity and spatial distribution of pin (sharp) sensation loss in the foot and leg and focuses less on motor weakness. The UENS utilizes a numeric scale from 0-42, with higher scores indicating greater disease severity.

Trial Locations

Locations (35): Coastal Carolina Research Center
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North Charleston, South Carolina, United States
Physicians Research Associates, LLC
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Lawrenceville, Georgia, United States
Triad Clinical Trials
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Greensboro, North Carolina, United States
Innovative Research of West Florida Inc
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Clearwater, Florida, United States
Torrance Clinical Research Institute Inc
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Lomita, California, United States
NY Scientific
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Brooklyn, New York, United States
Tandem Clinical Research
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Marrero, Louisiana, United States
Metabolic Research Institute Inc
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West Palm Beach, Florida, United States
The Center for Clinical Research
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Winston-Salem, North Carolina, United States
Diablo Clinical Research Inc
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Walnut Creek, California, United States
ClinCloud LLC
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Maitland, Florida, United States
Sensible Healthcare LLC
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Ocoee, Florida, United States
MediSphere Medical Research Center, LLC
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Evansville, Indiana, United States
Palmetto Clinical Research
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Summerville, South Carolina, United States
International Research Associates LLC
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Miami, Florida, United States
Sun Research Institute
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San Antonio, Texas, United States
Center for Clinical Research Inc
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San Francisco, California, United States
Wasatch Clinical Research LLC
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Salt Lake City, Utah, United States
Progressive Medical Research
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Port Orange, Florida, United States
Meridien Research
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Tampa, Florida, United States
National Research Institute
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Huntington Park, California, United States
Pinnacle Research Group LLC
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Anniston, Alabama, United States
Altman Clinical and Translational Research Institute
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La Jolla, California, United States
Arizona Research Center
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Phoenix, Arizona, United States
Diabetes/Lipid Management & Research Center
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Huntington Beach, California, United States
Providence Clinical Research
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North Hollywood, California, United States
DeLand Clinical Research Unit
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Lake Mary, Florida, United States
APF Research LLC
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Miami, Florida, United States
Rocky Mountain Clinical Research
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Idaho Falls, Idaho, United States
Olive Branch Family Medical Center
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Olive Branch, Mississippi, United States
Diabetes & Glandular Disease Clinic, P.A.
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San Antonio, Texas, United States
Advanced Biomedical Research of America
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Las Vegas, Nevada, United States
Hassman Research Institute
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Berlin, New Jersey, United States
Nerve and Muscle Center of Texas
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Houston, Texas, United States
FutureSearch Trials of Neurology
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Austin, Texas, United States