Clinical trial NCT02345291 (phase 2, status: completed)
Conditions: diabetic peripheral neuropathic pain
ICD codes: E85.1, E85.0, N31.0, N31.1, N31.2, E10.610, E11.610
Drugs: nrd135s.e1, placebo to match nrd135s.e1
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          1. -Males agree to use condoms throughout treatment and follow up study periods.

               -  Females must not be of childbearing potential as evidenced by at least one of the
                  following:

                  ≥ 62 years old and amenorrheic for ≥ 1 year

               -  Amenorrheic ≥ 12 consecutive months and a documented serum follicle stimulating
                  hormone (FSH) level > 35 mIU/mL

               -  Irregular menstrual periods and a documented FSH level > 35 mIU/mL

               -  On hormone replacement therapy and prior clinical evidence of menopause based on
                  any of the criteria above

               -  Surgically sterile

          2. Known stable diabetes mellitus for the last 3 months. (No oral hypoglycemic
             medications change allowed. Maximum insulin change allowed is ± 20%).

          3. Evidence of peripheral neuropathy associated with diabetes mellitus diagnosed by DN4
             criteria.

          4. Presence of ongoing pain due to DPN for at least 3 months.

          5. Mean DPN pain intensity of 4 to 9 on the NPS at screening.

          6. HbA1c ≤ 9% of total hemoglobin at screening.

          7. Willing to stop pain medications for DPN (except for limited use of paracetamol).

          8. Signed written informed consent.

               -  Subjects must have signed and dated an Institutional Review Board / Independent
                  Ethics Committee approved written informed consent form in accordance with
                  regulatory and institutional guidelines. This must be obtained before the
                  performance of any protocol related procedures that are not part of normal
                  subject care.

               -  Subjects must be willing and able to comply with scheduled visits, treatment
                  schedule, laboratory testing, and other requirements of the study.

        Exclusion Criteria

          1. Female of childbearing potential.

          2. Neurologic disorders unrelated to DPN that may interfere with the assessment of DPN.

          3. Known allergy or intolerance to paracetamol.

          4. Evidence of non-DPN polyneuropathy.

          5. The presence of severe pain associated with conditions other than DPN (e.g.,
             peripheral vascular disease, phantom pain, etc.) that could confound the
             self-evaluation of pain due to DPN.

          6. Any anti-epileptic or anti-depressive treatment. Amityptiline (Elatrol/Elatrolet) or
             duloxetine (Cymbalta) are permitted at screening but not later.

          7. Constant use of non-steroidal anti-inflammatory drugs or opiates that cannot be
             withdrawn during the washout period and the whole study duration.

          8. Participation in another clinical trial in the last 3 months.

          9. Poor compliance with prescribed medication or alcohol or drug abuse within 2 years
             before screening.

         10. Hypersensitivity to paracetamol or any of the inactive ingredients in NRD135S.E1
             capsules.

         11. Any serious medical condition, including the presence of laboratory abnormalities,
             that places the patient at an unacceptable risk if he or she participates in this
             study or confounds the ability to interpret data from the study.

         12. Patients with any hematological disorder.

         13. Prisoners or subjects who are involuntarily incarcerated.

         14. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (e.g. infectious disease) illness.

         15. Patients whose judgment has been impaired by their physical ir mental condition