Efficacy and Safety of NYX-2925 in Subjects With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy

This is a randomized, double-blind, parallel-group, placebo-controlled, multiple-dose study
to assess the efficacy and safety of NYX-2925 in subjects with neuropathic pain associated
with diabetic peripheral neuropathy.

The study will be a 6 to 9-week study, including a 1 to 4-week (dependent on duration of
washout period) Screening Period, followed by a 4-week double-blind, randomized,
placebo-controlled Treatment Period, and a 1-week Follow Up Period. Subjects eligible for the
study will randomize to receive either NYX-2925 or placebo for 4 weeks.

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 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 S-STS (Sheehan - Suicidality
Tracking Scale) at Visit 1 or Visit 2.

Waivers to the exclusion criteria will NOT be allowed.