Fibromyalgia
Conditions
Keywords
Fibromyalgia
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.
Interventions
DRUGNYX-2925
NYX-2925 is a novel small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).
DRUGPlacebo oral capsule
Matching placebo capsules.
Sponsors
inVentiv Health Clinical
Aptinyx
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Subjects are masked to the sequence in which they are taking placebo QD, NYX-2925 20 mg QD, NYX-2925 200 mg QD.
Intervention 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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
Approximately 24 subjects were planned to be enrolled. Twenty-two (22) subjects were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| All Treated Subjects Subjects received Placebo, 20 mg NYX-2925 QD, and 200 mg NYX-2925 QD | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | All Treated Subjects |
|---|---|
| Age, Continuous | 47.3 years STANDARD_DEVIATION 15.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fibromyalgia disease history, years | 14.57 years STANDARD_DEVIATION 14.476 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 7 / 22 |
| serious Total, serious adverse events | 0 / 22 |
Outcome results
Primary
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.
Time frame: Week 2, Week 4, and Week 6
Population: Population includes study subjects with analyzable images (n=19)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Treated Subjects | 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. | pINS mean placebo | 1.993 ratio | Standard Deviation 0.13981 |
| All Treated Subjects | 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. | pINS mean NYX-2925 20 mg | 1.911 ratio | Standard Deviation 0.14242 |
| All Treated Subjects | 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. | pINS NYX-2925 200 mg | 1.903 ratio | Standard Deviation 0.16194 |
Comparison: placebo - NYX-2925 200 mgp-value: 0.039t-test, 2 sided
Primary
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.
Time frame: Week 2, Week 4, Week 6
Population: Population includes study subjects with analyzable images (n=20)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Treated Subjects | 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. | dACC mean placebo | 2.1670 ratio | Standard Deviation 0.17796 |
| All Treated Subjects | 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. | dACC mean NYX-2925 20 mg | 2.0550 ratio | Standard Deviation 0.1971 |
| All Treated Subjects | 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. | dACC NYX-2925 200 mg | 2.0975 ratio | Standard Deviation 0.19141 |
Comparison: placebo - NYX-2925 20 mgp-value: 0.032t-test, 2 sided
Other Pre-specified
Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours
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.
Time frame: Change from Baseline, Week 2 (Placebo), Week 4, and Week 6 (NYX-2925)
Population: The efficacy population is based on subjects included in the safety population and have at least one post-baseline visit after receiving NYX-2925 20 mg PO QD.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Treated Subjects | Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours | Baseline | 5.32 units on a scale | Standard Deviation 1.411 |
| All Treated Subjects | Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours | Week 2 | 4.82 units on a scale | Standard Deviation 1.275 |
| All Treated Subjects | Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours | Week 4 | 4.74 units on a scale | Standard Deviation 1.36 |
| All Treated Subjects | Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours | Week 6 | 4.12 units on a scale | Standard Deviation 1.65 |
p-value: 0.0072t-test, 2 sided