EPPIC-Net: Novaremed Painful Diabetic Peripheral Neuropathy ISA

NCT ID: NCT05480228

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-21
• Study Completion Date: 2025-08-31

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.

Detailed Description

This ISA describes a double-blind Phase II study of the PK/PD, safety, tolerability, and effect of 13 weeks of NRD135S.E1 (80mg/day) as an ISA within the context of the Platform Protocol to Assess Treatments for Painful Diabetic Peripheral Neuropathy, EN21-PP. The ISA is intended to be read and interpreted within the context of the Platform Protocol and focuses on the description of design features that are specific to NRD135S.E1.

Conditions

Painful Diabetic Neuropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

NRD135S.E1 80mg/day

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.

Group Type: EXPERIMENTAL

NRD135SE.1

Intervention Type: DRUG

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

Matching placebo

A matching placebo comparator will be used.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Interventions

NRD135SE.1

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

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

NRD135s.E1, a small chemical entity for treatment of neuropathic pain

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

1. 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.**

2. 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.**

3. Any of the following conditions related to corrected QT intervals using Fridericia's formula (QTcF):

1. A QTcF > 500 ms prior to starting IP, up to and including the V3 pre-dose ECG.

2. A history of the following additional risk factors for torsade de pointes: heart failure, hypokalemia, history or family history of long QT syndrome.

4. History of myocardial infarction, other clinically active significant heart disease, or stroke. **This criterion is more stringent than a related Platform Protocol criterion.**

5. Participants known to have participated in four or more studies for investigational pain drugs.

6. 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.

7. Known hypersensitivity or contraindication to any excipients of the study drug formulation.

8. Taking prohibited medications as described in Appendix A, "Prohibited Medications."

9. 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:

1. 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);

2. 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;

3. A lifetime history of suicide attempt (V1).

10. Previous known or possible exposure to NRD135S.E1.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York University

OTHER

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

James P. Rathmell, MD

OTHER

Sponsor Role: lead

Responsible Party

James P. Rathmell, MD

Chair, Department of Anesthesiology, Perioperative and Pain Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jessica Robinson-Papp, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

University of California, San Diego

San Diego, California, United States

South Lake Pain Institute

Clermont, Florida, United States

SIMEDHealth LLC

Gainesville, Florida, United States

University of Florida

Gainesville, Florida, United States

Northwestern Department of Neurology

Chicago, Illinois, United States

Healthcare Research Network (Flossmoor)

Flossmoor, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

University of Maryland - Baltimore

Baltimore, Maryland, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

MGH Department of Anesthesia, Critical Care, and Pain

Boston, Massachusetts, United States

Healthcare Research Network (Hazelwood)

Hazelwood, Missouri, United States

NYU Langone Manhattan

New York, New York, United States

Mount Sinai School of Medicine

New York, New York, United States

Columbia University Medical Center/Neurological Institute

New York, New York, United States

University of Rochester

Rochester, New York, United States

Clinical Inquest Center

Beavercreek, Ohio, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Low Country Pain Center

Orangeburg, South Carolina, United States

American Indian Clinical Trials Research Network

Rapid City, South Dakota, United States

Nerve and Muscle Center of Texas

Houston, Texas, United States

Clinicore International

Houston, Texas, United States

University of Utah School of Medicine

Salt Lake City, Utah, United States

Eastern Virginia Medical School

Norfolk, Virginia, United States

VCU Department of Neurology

Richmond, Virginia, United States

University of Washington

Seattle, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20202753 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34316322 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21494314 (View on PubMed)

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/

Reference Type: BACKGROUND

Other Identifiers

OT2NS122680-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2022P002381 (EN21-01)

Identifier Type: -

Identifier Source: org_study_id