Ricolinostat in Patients With Painful Diabetic Peripheral Neuropathy

Painful Diabetic Peripheral Neuropathy Clinical Trial

Official title:

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of Ricolinostat in Patients With Painful Diabetic Peripheral Neuropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03176472
• Other study ID #: REGY-DN-201
• Status: Completed
• Phase: Phase 2
• Start date: December 7, 2020
• Est. completion date: April 28, 2023

Study information

• Verified date: September 2023
• Source: Regenacy Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: April 28, 2023
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• ricolinostat
120 mg per dose in 12 mL liquid formulation
• Placebo
12 mL liquid formulation placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Regenacy Pharmaceuticals LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Mean Average Pain Intensity (NRS)	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.	Baseline week [Day-7 to Day 1] compared to Final week [12 Weeks]
Secondary	Change in Non-pain Neuropathic Signs (UENS)	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.	Baseline week [Day-7 to Day 1] compared to Week 12