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Investigating a new treatment for painful diabetic neuropathy

EPPIC-Net EN21-01 A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of 80 mg Daily of NRD135S.E1 Versus Placebo in Adult and Elderly Participants With Painful Diabetic Peripheral Neuropathy.

Phase 2 Interventional Massachusetts General Hospital · NCT05480228

This study is testing a new capsule treatment for people with painful diabetic neuropathy to see if it can help relieve their pain better than a placebo.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment122 (estimated)
Ages18 Years and up
SexAll
SponsorMassachusetts General Hospital Academic / other
Locations26 sites (San Diego, California and 25 other locations)
Trial IDNCT05480228 on ClinicalTrials.gov

What this trial studies

This Phase II clinical trial evaluates the safety and efficacy of NRD135S.E1, a hard gelatin capsule formulation, administered at a dose of 80 mg once daily for 13 weeks in patients with painful diabetic peripheral neuropathy (PDPN). The study employs a double-blind design, comparing the active treatment to a placebo, and focuses on pharmacokinetics, pharmacodynamics, safety, and tolerability. Participants will be monitored for pain relief and other relevant outcomes throughout the trial period.

Who should consider this trial

Good fit: Ideal candidates include adults diagnosed with painful diabetic peripheral neuropathy who meet specific inclusion criteria related to pain levels.

Not a fit: Patients with conditions that may confound the results or those who do not meet the stringent eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly alleviate pain for patients suffering from diabetic peripheral neuropathy.

How similar studies have performed: Previous studies have shown promise in treating painful diabetic neuropathy, but this specific approach with NRD135S.E1 is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
7.1 ISA-Specific Inclusion Criteria (To be used in conjunction with Platform Protocol criteria; note, some ISA criteria may be more stringent than Platform criteria; always follow the more stringent criteria when determining eligibility.)

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.

Waivers to the inclusion criteria will not be allowed. 7.2 ISA-Specific Exclusion Criteria (To be used in conjunction with Platform Protocol criteria; note, some ISA criteria may be more stringent than Platform criteria; always follow the more stringent criteria when determining eligibility.) Participants fulfilling any of the following criteria are not eligible for the study.

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.

Waivers to the exclusion criteria will not be allowed.

Where this trial is running

San Diego, California and 25 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Painful Diabetic Neuropathy
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.