Evaluate the Efficacy and Safety of NYX-2925 in Subjects With Fibromyalgia

This is a single-blind, exploratory, placebo-controlled, pilot study to assess the efficacy and safety of daily oral NYX-2925 in fibromyalgia subjects. The study will include a screening period (up to 30 days), a placebo period, an active treatment period with, and a follow-up period as follows:

* Placebo PO Every Day (QD) for 2 weeks
* NYX-2925 PO QD for 2 weeks (2x)
* Follow-up for 1 week

Eligible subjects will receive MRIs during the screening period, during the placebo period, during the NYX-2925 PO QD period. Safety assessments will be conducted and adverse events will be collected during the study. Daily pain scores and other fibromyalgia scales will be collected during the study. Daily pain scores and other fibromyalgia scales will be collected for exploratory analysis. During the follow-up period, an optional MRI will be completed for consenting subjects in order to evaluate duration of effect.

• NYX-2925 (Drug): NYX-2925 is a novel small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).
• Placebo oral capsule (Drug): Matching placebo capsules.

Primary outcomes

• Mean (SD) Glx/Total Creatine Levels in Dorsal Anterior Cingulate Cortex (dACC): NYX-2925 20 mg and 200 mg PO QD at Week 4 and Week 6, Respectively. [Week 2, Week 4, Week 6]
• Mean (SD) Changes in Posterior Insula (pINS) Glx/Total Creatine Levels Before and After Acute Painful Pressure Stimulation: NYX-2925 20 mg and 200 mg PO QD at Week 4 and Week 6, Respectively. [Week 2, Week 4, and Week 6]

Other outcomes

• Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours [Change from Baseline, Week 2 (Placebo), Week 4, and Week 6 (NYX-2925)]: Numeric pain rating scale is a unidimensional segmented numeric version of the visual analog scale. A subject selects a whole number (0 to 10) that best indicates the intensity of their pain, where 0 represents no pain and 10 the worst pain imaginable.

Sex: Female, ages: 18 Years to 70 Years

Inclusion Criteria:

1. Subjects meets the 2010 American College of Rheumatology (ACR) criteria for fibromyalgia.
2. Self-reported clinical pain ≥ 4 and on the Numeric Pain Rating Scale (NPRS) at screening and baseline.
3. Subject receives and agrees to remain on their stable fibromyalgia treatment plan established at least 14 days prior to dosing.
4. Subject agrees to use only non-steroidal anti-inflammatory (NSAID) or acetaminophen treatment as needed for breakthrough pain, and/or, zopiclone, zolpidem, zaleplon, or eszopiclone for sleep (if needed).
5. Right handed.
6. Calculates creatinine clearance ≥ 60 mL/minute.
7. Female subjects of child bearing potential with a negative serum pregnancy test prior to entry into the study and who are practicing an adequate method of birth control (e.g., surgical sterilization, oral or parenteral contraceptives, intrauterine device that is considered safe for MRI procedures, barrier \[condom with spermicide\]) and who do not plan to become pregnant, breastfeed, or donate ova during the course of the study and for 28 days after the final administration of investigational product.
8. Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments.

Exclusion Criteria:

1. Current or expected use of opioid or narcotic analgesics, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, gabapentins, topiramate, anticonvulsants, benzodiazepines, and sedatives, or hypnotics.
2. Unstable doses of allowed antidepressants or muscle relaxants. Use of NSAIDs or acetaminophen 24 hours prior to imaging procedures is prohibited.
3. Pain due to concurrent disease such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, or other chronic widespread pain condition(s) that may confound fibromyalgia pain.
4. Untreated endocrine disorder that may confound fibromyalgia assessments.
5. Psychiatric or cognitive disorder (e.g., current schizophrenia, severe depression, suicidal ideation, dementia, etc.).
6. Clinically significant alcohol or other substance abuse within the last 2 years.
7. Positive screen for medically inappropriate or illegal use of drugs of abuse.
8. Current treatment with medications such as ketamine, amantadine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.
9. History of allergy, sensitivity, or intolerance to medications such as ketamine, amantadine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.
10. Women, who are pregnant, breast feeding, or planning to become pregnant or donate ova during the course of the study and for 28 days after the final administration of investigational product.
11. Huntington's, Parkinson's, Alzheimer's, Multiple Sclerosis, or history of seizures, epilepsy, or strokes.
12. Contraindications to fMRI procedures. These may include but are not limited to: surgical clips, surgical staples, metal implants, and certain metallic dental material.
13. Current or habitual use (within the last 12 months) of artificial nails, nails enhancements, or nail extensions that cover any portion of either thumbnail.
14. Abnormal laboratory results, medical history, or concurrent conditions that would preclude safe study participation, or interfere with study procedures/assessments.
15. Impaired liver function.
16. Known history of significant heart condition or high blood pressure.
17. Current evidence of dysplasia or history of cancer malignancy (including lymphoma and leukemia) in the last 5 years.
18. Human immunodeficiency virus (HIV) infection, hepatitis, or other ongoing infectious disease.
19. History of severe kidney or liver impairment.
20. History of migraine.
21. History of lower limb vascular surgery or current lower limb vascular dysfunction.
22. Received an investigational drug or device within 30 days of dosing.
23. Previous treatment with NYX-2925.
24. Resting heart rate < 45 or ≥ 95 beats per minute.

Participant flow

Outcome results

• Mean (SD) Glx/Total Creatine Levels in Dorsal Anterior Cingulate Cortex (dACC): NYX-2925 20 mg and 200 mg PO QD at Week 4 and Week 6, Respectively. (Primary), Mean, ratio: All Treated Subjects 2.1670 +/- 0.17796 (p 0.032)
• Mean (SD) Changes in Posterior Insula (pINS) Glx/Total Creatine Levels Before and After Acute Painful Pressure Stimulation: NYX-2925 20 mg and 200 mg PO QD at Week 4 and Week 6, Respectively. (Primary), Mean, ratio: All Treated Subjects 1.993 +/- 0.13981 (p 0.039)
• Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours (Other pre specified), Mean, units on a scale: All Treated Subjects 5.32 +/- 1.411 (p 0.0072)

Adverse events

Time frame: Adverse events were collected from the time the informed consent was signed to the end of the subject's participation in the study (Week 7).

Other adverse events by term

• Study Protocol (PDF, 2018-03-07)
• Statistical Analysis Plan (PDF, 2018-11-26)