EPPIC-Net: Novaremed Painful Diabetic Peripheral Neuropathy ISA

NCT05480228 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 2022P002381 (EN21-01)OT2NS122680-01
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 26

Brief Summary

The purpose of this study is to investigate the safety and efficacy of the current hard gelatin capsule formulation of NRD135S.E1 80 mg once daily in the treatment of PDPN when administered for 13 weeks.

Conditions

Painful Diabetic Neuropathy

Outcome Measures

Primary Outcomes (2)

• To demonstrate that NRD135S.E1 80 mg daily is superior to placebo in relieving neuropathic pain associated with PDPN, after 13 weeks' treatment.

  Change from Baseline to Week 13 in the weekly mean of the daily 24-hour average pain measured by Numeric Rating Scale (NRS) (abbreviated herein as WAP for weekly average pain). The NRS is a 0-10 scale, with 0 indicating no pain, and 10 being the worst possible pain.

  13 weeks

• The frequency (i.e. number of participants) with treatment emergent adverse events (TEAEs) reported in the time period defined by first administration of IP until 7 days after the last dose of IP.

  A treatment-emergent adverse event (TEAE) is any AE temporally associated with the use of study treatment whether or not considered by the investigator as related to study treatment.

  13 weeks

Secondary Outcomes (2)

• Occurrence of 30% reduction of WAP from Baseline to Week 13.

  13 weeks

• Occurrence of 50% reduction of WAP from Baseline to Week 13.

  13 weeks

Other Outcomes (13)

• To assess the effect of NRD135S.E1 in comparison to placebo with respect to Pain Catastrophizing Scale - Short Form 6 (PCS-SF6)

  13 weeks

• To assess the effect of NRD135S.E1 in comparison to placebo with respect to the Pain, Enjoyment, and General activity scale (PEG).

  13 weeks

• To assess the effect of NRD135S.E1 in comparison to placebo with respect to the PROMIS Physical Functioning Short-Form 6b

  13 weeks

Study Arms (2)

NRD135S.E1 80mg/day

EXPERIMENTAL

NRD135S.E1 as a potential treatment for moderate to severe painful diabetic peripheral neuropathy (PDPN). While the activity of NRD135S.E1 has been extensively studied, its molecular target is not known, though it does not appear to work through any of the opioid receptors or molecular pathways currently targeted by available analgesics. The best evidence suggests it may act, at least in part, through modulating the Lyn kinase signaling pathway In clinical studies, NRD135S.E1 has been well tolerated at all dose levels tested in single-dose (up to 1,200 mg) and repeat-dose regimens (up to 300 mg/day over 5 days or 150 mg over 3 weeks), and it has been shown to have predictable pharmacokinetics with dose-dependent increases in exposure.

Drug: NRD135SE.1

Matching placebo

PLACEBO COMPARATOR

A matching placebo comparator will be used.

Other: Placebo

Interventions

NRD135SE.1 DRUG

The double-blind treatment phase is up to 13 weeks.

Also known as: NRD135s.E1, a small chemical entity for treatment of neuropathic pain

NRD135S.E1 80mg/day

Placebo OTHER

A matching placebo will be taken for up to 13 weeks.

Matching placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provides written consent for the EN21-01 ISA. Legally Authorized Representatives (LARs) are not allowed, but impartial witnesses may be utilized as needed for visually impaired participants.
• Patient-reported daily 11-point NRS (for average pain over the last 24 hours) meets the criteria specified in "Appendix B: Blinded Information" during both the 7-day screening and 7-day baseline periods. The algorithm will be assessed centrally.

You may not qualify if:

• Diagnosis of alcohol or substance abuse or dependence (other than nicotine or caffeine) within the 2 years before the Screening visit. \*\*This criterion is more stringent than a related Platform Protocol criterion.\*\*
• Moderate or severe renal impairment, known (documented) or defined as an estimated/calculated creatinine clearance/estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73 m2, according to the Chronic Kidney Disease Epidemiology Collaboration formula during the screening process. \*\*This criterion is more stringent than a related Platform Protocol criterion.\*\*
• Any of the following conditions related to corrected QT intervals using Fridericia's formula (QTcF):
• A QTcF \> 500 ms prior to starting IP, up to and including the V3 pre-dose ECG.
• A history of the following additional risk factors for torsade de pointes: heart failure, hypokalemia, history or family history of long QT syndrome.
• History of myocardial infarction, other clinically active significant heart disease, or stroke. \*\*This criterion is more stringent than a related Platform Protocol criterion.\*\*
• Participants known to have participated in four or more studies for investigational pain drugs.
• Participants known to be non-responders to more than three previous neuropathic pain medications at adequate doses over at least 4 weeks. Adequate doses (given as total daily doses) are defined as follows: 1,800 mg gabapentin; 300 mg pregabalin; opioid analgesics 60 mg oxycodone equivalent or 200 mg tramadol; 75 mg amitriptyline or equivalent tricyclic antidepressant; 60 mg duloxetine; 150 mg venlafaxine.
• Known hypersensitivity or contraindication to any excipients of the study drug formulation.
• Taking prohibited medications as described in Appendix A, "Prohibited Medications."
• Major depressive episode within the 6 months before screening and/or a history of diagnosed recurrent major depressive disorder within two years. Any of the following conditions related to suicidality:
• Any suicidal ideation with intent, with or without a plan, at screening, i.e., answering "yes" to questions 4 or 5 on the Suicidal Ideation section of the Baseline/Screening version of the Columbia-Suicide Severity Rating Scale (C-SSRS);
• Answering "yes" on any item of the Suicidal Behavior Section (except for the "non-suicidal self-injurious behavior") of the C-SSRS if this behavior occurred in the past 2 years;
• A lifetime history of suicide attempt (V1).
• Previous known or possible exposure to NRD135S.E1.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: collaborator
• New York University: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• James P. Rathmell, MD: lead

Study Sites (26)

University of California, San Diego

San Diego, California, 92037, United States

Location

South Lake Pain Institute

Clermont, Florida, 34711, United States

Location

SIMEDHealth LLC

Gainesville, Florida, 32607, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Northwestern Department of Neurology

Chicago, Illinois, 60611, United States

Location

Healthcare Research Network (Flossmoor)

Flossmoor, Illinois, 60422, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Maryland - Baltimore

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

MGH Department of Anesthesia, Critical Care, and Pain

Boston, Massachusetts, 02114, United States

Location

Healthcare Research Network (Hazelwood)

Hazelwood, Missouri, 63042, United States

Location

NYU Langone Manhattan

New York, New York, 10017, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Columbia University Medical Center/Neurological Institute

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14627, United States

Location

Clinical Inquest Center

Beavercreek, Ohio, 45431, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

Low Country Pain Center

Orangeburg, South Carolina, 29118, United States

Location

American Indian Clinical Trials Research Network

Rapid City, South Dakota, 57701, United States

Location

Nerve and Muscle Center of Texas

Houston, Texas, 77030, United States

Location

Clinicore International

Houston, Texas, 77077, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23510, United States

Location

VCU Department of Neurology

Richmond, Virginia, 23298, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

University of Wisconsin

Madison, Wisconsin, 53706, United States

Location

Related Publications (4)

• Dworkin RH, Turk DC, Peirce-Sandner S, McDermott MP, Farrar JT, Hertz S, Katz NP, Raja SN, Rappaport BA. Placebo and treatment group responses in postherpetic neuralgia vs. painful diabetic peripheral neuropathy clinical trials in the REPORT database. Pain. 2010 Jul;150(1):12-16. doi: 10.1016/j.pain.2010.02.002. Epub 2010 Mar 3. No abstract available.

  PMID: 20202753 BACKGROUND

• Tarpey T, Petkova E, Ciarleglio A, Ogden RT. Extracting scalar measures from functional data with applications to placebo response. Stat Interface. 2021;14(3):255-265. doi: 10.4310/20-sii633.

  PMID: 34316322 BACKGROUND

• Tarpey T, Petkova E, Lu Y, Govindarajulu U. Optimal Partitioning for Linear Mixed Effects Models: Applications to Identifying Placebo Responders. J Am Stat Assoc. 2010 Jan 1;105(491):968-977. doi: 10.1198/jasa.2010.ap08713.

  PMID: 21494314 BACKGROUND

• Van Buuren, S., & Groothuis-Oudshoorn, K. (2011). Journal of Statistical Software mice: Multivariate Imputation by Chained Equations in R (Vol. 45). http://www.jstatsoft.org/

  BACKGROUND

MeSH Terms

Conditions

Diabetic Neuropathies

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Jessica Robinson-Papp, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization assignment will be blinded from study participants, staff from clinical sites, investigators, asset owner, IND sponsors, and/or designees.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chair, Department of Anesthesiology, Perioperative and Pain Medicine

Model Details: This study is an interventional, prospective, parallel-group, multicenter, randomized, double-blind, placebo-controlled, Phase 2 study.

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: July 29, 2022
• Study Start: September 21, 2022
• Primary Completion: August 31, 2025
• Study Completion: August 31, 2025
• Last Updated: March 19, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (26)