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

Study Overview
=================
Brief Summary
-----------------
The primary objective is to determine whether daily dosing with NYX-2925 changes markers of central pain processing in subjects with fibromyalgia by evaluating changes in evoked pain, and visual stimulation, functional magnetic resonance imaging (fMRI), resting state function connectivity magnetic resonance imaging (rs-fcMRI) and proton magnetic resonance spectroscopy (H-MRS) in fibromyalgia subjects on active drug versus placebo.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase 2, Single-Blind, Exploratory, Placebo-controlled, Pilot Study to Assess the Efficacy and Safety of Daily Oral NYX-2925 in Subjects With Fibromyalgia

Conditions
-----------------
Fibromyalgia

Intervention / Treatment
-----------------
* Drug: NYX-2925
* Drug: Placebo oral capsule


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects meets the 2010 American College of Rheumatology (ACR) criteria for fibromyalgia. Self-reported clinical pain ≥ 4 and on the Numeric Pain Rating Scale (NPRS) at screening and baseline. Subject receives and agrees to remain on their stable fibromyalgia treatment plan established at least 14 days prior to dosing. 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). Right handed. Calculates creatinine clearance ≥ 60 mL/minute. 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. 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: Current or expected use of opioid or narcotic analgesics, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, gabapentins, topiramate, anticonvulsants, benzodiazepines, and sedatives, or hypnotics. Unstable doses of allowed antidepressants or muscle relaxants. Use of NSAIDs or acetaminophen 24 hours prior to imaging procedures is prohibited. 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. Untreated endocrine disorder that may confound fibromyalgia assessments. Psychiatric or cognitive disorder (e.g., current schizophrenia, severe depression, suicidal ideation, dementia, etc.). Clinically significant alcohol or other substance abuse within the last 2 years. Positive screen for medically inappropriate or illegal use of drugs of abuse. Current treatment with medications such as ketamine, amantadine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone. History of allergy, sensitivity, or intolerance to medications such as ketamine, amantadine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone. 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. Huntington's, Parkinson's, Alzheimer's, Multiple Sclerosis, or history of seizures, epilepsy, or strokes. Contraindications to fMRI procedures. These may include but are not limited to: surgical clips, surgical staples, metal implants, and certain metallic dental material. Current or habitual use (within the last 12 months) of artificial nails, nails enhancements, or nail extensions that cover any portion of either thumbnail. Abnormal laboratory results, medical history, or concurrent conditions that would preclude safe study participation, or interfere with study procedures/assessments. Impaired liver function. Known history of significant heart condition or high blood pressure. Current evidence of dysplasia or history of cancer malignancy (including lymphoma and leukemia) in the last 5 years. Human immunodeficiency virus (HIV) infection, hepatitis, or other ongoing infectious disease. History of severe kidney or liver impairment. History of migraine. History of lower limb vascular surgery or current lower limb vascular dysfunction. Received an investigational drug or device within 30 days of dosing. Previous treatment with NYX-2925. Resting heart rate < 45 or ≥ 95 beats per minute.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects will receive placebo, NYX-2925 20 mg QD, NYX-2925 200 mg QD for sequential 2 week treatment periods, then go into Follow-up for 1 week.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All subjects<br>Up to 24 subjects will receive placebo, NYX-2925 20 mg QD, and NYX-2925 200 mg QD for sequential 2 week treatment periods, then go into Follow-up for 1 week. | Drug: NYX-2925<br>* NYX-2925 is a novel small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).<br>Drug: Placebo oral capsule<br>* Matching placebo capsules.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fibromyalgia