Efficacy and Safety of NYX-2925 in Subjects With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
Condition: Diabetic Peripheral Neuropathy
MeSH terms: Peripheral Nervous System Diseases; Neuralgia; Diabetic Neuropathies
Intervention: NYX-2925; Placebo
Intervention description: NYX-2925 is a novel small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).; Matching Placebo capsules.
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be randomized to receive placebo or NYX-2925.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Treatment arms, dose levels, and randomization algorithm are masked.
Enrollment: 301.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Type 2 Diabetes; Neuropathic Pain; Peripheral Nervous System

Summary:

      To evaluate the efficacy of multiple dose levels of NYX-2925 versus placebo in treating the
      neuropathic pain associated with Diabetic Peripheral Neuropathy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. An Institutional Review Board-approved written informed consent and privacy language
             (Health Insurance Portability and Accountability Act) authorization must be obtained
             from the subject prior to performing any study-related procedures.

          2. Subjects who consent to being included in a subject registry database.

          3. Male and female subjects ≥18 and ≤75 years of age.

          4. Subjects with a diagnosis of Type 2 diabetes.

          5. Subjects with a score of ≥4 and ≤9 on the 11-point numeric rating scale (NRS) for
             average pain intensity over the past 24 hours at Visit 1.

          6. Hemoglobin A1c (HbA1c) ≤11% (measured at Visit 1).

          7. Stable use of diabetic medications beginning 1 month prior to Visit 1 (Adequate
             glycemic control with only diet and exercise is also permitted.).

          8. Subjects with diabetic peripheral neuropathy, of symmetrical nature and in lower
             extremities for ≥6 months to ≤10 years, and diagnosed by a score of ≥3 on Michigan
             Neuropathy Screening Instrument.

          9. Body mass index of <40 kg/m^2

         10. Calculated creatinine clearance of ≥60 mL/minute (Cockcroft-Gault formula).

         11. Clinical laboratory values must be within normal limits or deemed not clinically
             significant by the investigator and sponsor-designated medical monitor.

        Inclusion Criteria: Randomization Daily pain scores and diary compliance will be
        transferred into the interactive response technology system, which will assess the criteria
        for randomization. Subjects whose mean of the daily average pain intensity score during the
        preceding 7 (±1) days is within the protocol-defined algorithm and with adequate compliance
        with daily diary completion will be eligible for randomization.

        Waivers to the inclusion criteria will NOT be allowed.

        Exclusion Criteria:

          1. Subjects who have a current diagnosis of major psychiatric disorder (including
             schizophrenia, bipolar disorder, or panic disorder), including those who have required
             an antipsychotic or mood stabilizer (e.g., lithium, carbamazepine, valproate) for a
             psychiatric condition in the past year, or subjects who have had a major depressive
             episode (MDE) in the past 6 months. Subjects with major depressive disorder (MDD) or
             generalized anxiety disorder (GAD) who have been on stable medications for the past 3
             months (and are expected to remain stable for the duration of the trial) and whose
             condition is currently well-controlled may be included.

          2. Subjects who have pain that cannot be clearly differentiated from, or could interfere
             with the assessment of peripheral diabetic neuropathy, as measured by the Masquerading
             Disorders Tool at Visit 1.

          3. Neurologic disorders unrelated to diabetic neuropathy (e.g., phantom limb from
             amputation), skin condition in the area of neuropathy that could alter sensation
             (e.g., plantar ulcer), or other painful conditions (e.g., arthritis) that, in the
             judgment of the investigators, could interfere with reporting of pain due to diabetic
             neuropathy.

          4. History of hypoglycemia that disturbed consciousness, or ketoacidosis requiring
             hospitalization within past 3 months.

          5. Subjects with history of severe renal impairment.

          6. Impaired hepatic function.

          7. Known history of significant cardiovascular condition.

          8. History of Huntington's disease, Parkinson's disease, Alzheimer's disease, Multiple
             Sclerosis, or a history of seizures, epilepsy, or strokes.

          9. HIV infection, hepatitis, or other ongoing infectious disease that the investigator
             considers clinically significant.

         10. Concomitant use of antiepileptic drugs, non-steroidal anti-inflammatory drugs (except
             cardiac preventive acetylsalicylic acid), opioids, muscle relaxants, dextromethorphan
             (except low dose intermittent use for cough), tramadol, topical lidocaine, topical
             capsaicin, and selective norepinephrine reuptake inhibitors. Subjects are allowed to
             enter with a maximum of 1 allowed analgesic medication for neuropathic pain that has
             been taken at stable dose for at least 1 month (30 days) prior to Visit 1. Allowed
             analgesics may not be N-methyl-D-aspartate receptor ligands, must be non-opioid and
             non-sedative and must not interfere with subjects' pain reporting. Tricyclic
             antidepressants may be continued if designated as the single analgesic medication for
             the treatment of pain.

         11. Sensitivity to, allergy to, or concomitant use of N-methyl-D-aspartate receptor
             ligands including ketamine, amantadine, dextromethorphan (except low dose intermittent
             use for cough), memantine, methadone, dextropropoxyphene, and/or ketobemidone.

         12. Amputations of lower extremities (toe amputation is allowed).

         13. Any condition, including serious medical conditions that could interfere with the
             ability of the subject to participate in the study or could confound study
             assessments.

         14. Subjects who meet the criteria for suicidal intent, plan and/or behavior by scoring 3
             or 4 on Questions 2 or 13, or 2 or higher on any Questions 1a (only if 1b is coded
             YES), 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 14 based on the Sheehan - Suicidality
             Tracking Scale at Visit 1 or Visit 2.

        Waivers to the exclusion criteria will NOT be allowed.