Clinical trial NCT03176472: Ricolinostat in Patients With Painful Diabetic Peripheral Neuropathy
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of Ricolinostat in Patients With Painful Diabetic Peripheral Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Painful Diabetic Peripheral Neuropathy
Keywords: Diabetic Neuropathic Pain
Neuropathic Pain
HDAC6
ricolinostat
Painful Diabetic Peripheral Neuropathy
DPN
Lead sponsor: Regenacy Pharmaceuticals LLC
Sponsor class: INDUSTRY
First posted: 2017-06-05
Enrollment: 282
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Mean Average Pain Intensity (NRS)
timeFrame: Baseline week [Day-7 to Day 1] compared to Final week [12 Weeks]
Secondary outcomes:
measure: Change in Non-pain Neuropathic Signs (UENS)
timeFrame: Baseline week [Day-7 to Day 1] compared to Week 12
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group LLC
state: Alabama
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Huntington Beach
country: United States
facility: Diabetes/Lipid Management & Research Center
state: California
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: La Jolla
country: United States
facility: Altman Clinical and Translational Research Institute
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute Inc
state: California
city: North Hollywood
country: United States
facility: Providence Clinical Research
state: California
city: San Francisco
country: United States
facility: Center for Clinical Research Inc
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research Inc
state: California
city: Clearwater
country: United States
facility: Innovative Research of West Florida Inc
state: Florida
city: Lake Mary
country: United States
facility: DeLand Clinical Research Unit
state: Florida
city: Maitland
country: United States
facility: ClinCloud LLC
state: Florida
city: Miami
country: United States
facility: APF Research LLC
state: Florida
city: Miami
country: United States
facility: International Research Associates LLC
state: Florida
city: Ocoee
country: United States
facility: Sensible Healthcare LLC
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute Inc
state: Florida
city: Lawrenceville
country: United States
facility: Physicians Research Associates, LLC
state: Georgia
city: Idaho Falls
country: United States
facility: Rocky Mountain Clinical Research
state: Idaho
city: Evansville
country: United States
facility: MediSphere Medical Research Center, LLC
state: Indiana
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Olive Branch
country: United States
facility: Olive Branch Family Medical Center
state: Mississippi
city: Las Vegas
country: United States
facility: Advanced Biomedical Research of America
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Brooklyn
country: United States
facility: NY Scientific
state: New York
city: Greensboro
country: United States
facility: Triad Clinical Trials
state: North Carolina
city: Winston-Salem
country: United States
facility: The Center for Clinical Research
state: North Carolina
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Summerville
country: United States
facility: Palmetto Clinical Research
state: South Carolina
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: Houston
country: United States
facility: Nerve and Muscle Center of Texas
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Clinic, P.A.
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research LLC
state: Utah
Study officials:
References: