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Painful Diabetic NeuropathyPhase 2EN21-01NCT05480228

EPPIC-Net: Novaremed Painful Diabetic Peripheral Neuropathy ISA

A Phase 2 study testing NRD135SE.1 in people with Painful Diabetic Neuropathy, run by James P. Rathmell, MD at 26 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Painful Diabetic Neuropathy
What is being tested?
NRD135SE.1
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
127 participants
Where
26 sitesUnited States
Study dates
21 Sep 2022to 31 Aug 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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):
  4. A QTcF > 500 ms prior to starting IP, up to and including the V3 pre-dose ECG.
  5. A history of the following additional risk factors for torsade de pointes: heart failure, hypokalemia, history or family history of long QT syndrome.
  6. History of myocardial infarction, other clinically active significant heart disease, or stroke. This criterion is more stringent than a related Platform Protocol criterion.
  7. Participants known to have participated in four or more studies for investigational pain drugs.
  8. 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.
  9. Known hypersensitivity or contraindication to any excipients of the study drug formulation.
  10. Taking prohibited medications as described in Appendix A, "Prohibited Medications."
  11. 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:
  12. 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);
  13. 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;
  14. A lifetime history of suicide attempt (V1).
  15. Previous known or possible exposure to NRD135S.E1.

Waivers to the exclusion criteria will not be allowed.

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

United States26 sites

  • University of Maryland - Baltimore

    Baltimore, Maryland, 21201

  • Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21205

  • Clinical Inquest Center

    Beavercreek, Ohio, 45431

  • MGH Department of Anesthesia, Critical Care, and Pain

    Boston, Massachusetts, 02114

  • Northwestern Department of Neurology

    Chicago, Illinois, 60611

  • South Lake Pain Institute

    Clermont, Florida, 34711

  • Healthcare Research Network (Flossmoor)

    Flossmoor, Illinois, 60422

  • SIMEDHealth LLC

    Gainesville, Florida, 32607

  • University of Florida

    Gainesville, Florida, 32611

  • Healthcare Research Network (Hazelwood)

    Hazelwood, Missouri, 63042

  • Nerve and Muscle Center of Texas

    Houston, Texas, 77030

  • Clinicore International

    Houston, Texas, 77077

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • University of Wisconsin

    Madison, Wisconsin, 53706

  • NYU Langone Manhattan

    New York, New York, 10017

  • Mount Sinai School of Medicine

    New York, New York, 10029

  • Columbia University Medical Center/Neurological Institute

    New York, New York, 10032

  • Eastern Virginia Medical School

    Norfolk, Virginia, 23510

  • Low Country Pain Center

    Orangeburg, South Carolina, 29118

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15260

  • American Indian Clinical Trials Research Network

    Rapid City, South Dakota, 57701

  • VCU Department of Neurology

    Richmond, Virginia, 23298

  • University of Rochester

    Rochester, New York, 14627

  • University of Utah School of Medicine

    Salt Lake City, Utah, 84132

  • University of California, San Diego

    San Diego, California, 92037

  • University of Washington

    Seattle, Washington, 98195

Other trials in United States

About this study

Official title: 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.

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.

Read the 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.

Being tested
NRD135SE.1, Placebo
Medical subject headings
Diabetic Neuropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NRD135SE.1Drug

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

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

  • PlaceboOther

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

Study groups in NCT05480228
Study groupRoleWhat they receive
NRD135S.E1 80mg/dayExperimentalNRD135S.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.
Receives: Drug: NRD135SE.1
Matching placeboPlacebo comparatorA matching placebo comparator will be used.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 13 weeks

  2. 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.

    Measured: 13 weeks

Secondary outcomes (2)

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

    Weekly Average Pain is abbreviated as WAP.

    Measured: 13 weeks

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

    Weekly Average Pain is abbreviated as WAP.

    Measured: 13 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2022
  2. Study start21 Sep 2022
  3. Primary completion31 Aug 2025
  4. Study completion31 Aug 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This study is an interventional, prospective, parallel-group, multicenter, randomized, double-blind, placebo-controlled, Phase 2 study.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
127 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05480228
Sponsor's protocol ID
2022P002381 (EN21-01)
Other IDs
OT2NS122680-01
Acronym
EN21-01
Status last verified
Oct 2025
First submitted
25 Jul 2022
Last updated
19 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: No The use of Global Unique Identifiers (GUIDs) allows data to be linked with a given research participant, without revealing any of the participant's identifiable information. All participants in NIH-funded research must have a GUID. This study is using the Biomedical Research Informatics Computing System (BRICS) GUID platform to assign GUIDs. This ID should be generated at the time of Informed Consent since it requires several pieces of patient information (e.g., last name at birth, first name at birth, sex at birth, day, month and year of birth, city and country of birth, etc.). The GUID will be a combination of letters and numbers to form a unique identifier, e.g. TBIAC412JJK. Sites should maintain a list to link the GUID to the participant.

Publications

  • 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.

    PubMed 20202753

  • 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.

    PubMed 34316322

  • 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.

    PubMed 21494314

  • 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/

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NRD135SE.1 in people with Painful Diabetic Neuropathy, run by James P. Rathmell, MD at 26 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To demonstrate that NRD135S.E1 80 mg daily is superior to placebo in relieving neuropathic pain associated with PDPN, after 13 weeks' treatment. (time frame: 13 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05480228, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.

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