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

• ClinicalTrials.gov Identifier: NCT03249103
• Recruitment Status: Completed
• First Posted: August 15, 2017
• Last Update Posted: June 25, 2019
• Sponsor: Aptinyx
• Collaborator: inVentiv Health Clinical
• Information provided by (Responsible Party): Aptinyx

Tracking Information

• First Submitted Date: August 2, 2017
• First Posted Date: August 15, 2017
• Last Update Posted Date: June 25, 2019
• Actual Study Start Date: August 14, 2017
• Actual Primary Completion Date: April 18, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 10, 2017): Changes in markers of central pain processing as measured by functional magnetic resonance imaging. [ Time Frame: Screening through Week 6 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 10, 2017)

• Evaluate safety as measured by the incidence of adverse events [ Time Frame: Screening through Week 7 ]
• Evaluate the safety as measure by the change in vital sign measurements [ Time Frame: Screening through Week 7 ]
• Evaluate the changes in clinical laboratory test results [ Time Frame: Screening through Week 7 ]
• Evaluate the changes in electrocardiogram results [ Time Frame: Screening through Week 7 ]
• Evaluate the changes in physical examination findings [ Time Frame: Screening through Week 7 ]
• Evaluating suicidal ideation and behavior as measure by the Columbia-Suicide Severity Rating Scale [ Time Frame: Screening through Week 7 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluate the Efficacy and Safety of NYX-2925 in Subjects With Fibromyalgia
• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

All subjects will receive NYX-2925 Low Dose, NYX-2925 High Dose, and placebo PO QD for 2 week treatment periods, then go into Follow-up for 1 week.

Masking: Single (Participant)
Masking Description:

Subjects are masked to when they taking NYX-2925 High Dose, NYX-2925 Low Dose, and Placebo.

Primary Purpose: Treatment

• Condition: Fibromyalgia

Intervention

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

Study Arms

• Placebo Comparator: Placebo
  Up to 24 subjects will receive Placebo, NYX-2925 Low Dose, and NYX-2925 High Dose
  Intervention: Drug: Placebo oral capsule
• Experimental: NYX-2925 High Dose
  Up to 24 subjects will receive High Dose of NYX-2925
  Intervention: Drug: NYX-2925
• Experimental: NYX-2925 Low Dose
  Up to 24 subjects will receive Low Dose of NYX-2925
  Intervention: Drug: NYX-2925

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 21, 2019): 22
• Original Estimated Enrollment (submitted: August 10, 2017): 24
• Actual Study Completion Date: April 18, 2019
• Actual Primary Completion Date: April 18, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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, gabapentinoids, 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03249103
• Other Study ID Numbers: NYX-2925-2002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Aptinyx
• Study Sponsor: Aptinyx
• Collaborators: inVentiv Health Clinical
• Investigators: Not Provided
• PRS Account: Aptinyx
• Verification Date: June 2019