<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03249103</url>
  </required_header>
  <id_info>
    <org_study_id>NYX-2925-2002</org_study_id>
    <nct_id>NCT03249103</nct_id>
  </id_info>
  <brief_title>Evaluate the Efficacy and Safety of NYX-2925 in Subjects With Fibromyalgia</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aptinyx</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>inVentiv Health Clinical</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Aptinyx</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective is to determine whether daily dosing with NYX-2925 changes markers of&#xD;
      central pain processing in subjects with fibromyalgia by evaluating changes in evoked pain,&#xD;
      and visual stimulation, functional magnetic resonance imaging (fMRI), resting state function&#xD;
      connectivity magnetic resonance imaging (rs-fcMRI) and proton magnetic resonance spectroscopy&#xD;
      (H-MRS) in fibromyalgia subjects on active drug versus placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-blind, exploratory, placebo-controlled, pilot study to assess the efficacy&#xD;
      and safety of daily oral NYX-2925 in fibromyalgia subjects. The study will include a&#xD;
      screening period (up to 30 days), a placebo period, an active treatment period with, and a&#xD;
      follow-up period as follows:&#xD;
&#xD;
        -  Placebo PO Every Day (QD) for 2 weeks&#xD;
&#xD;
        -  NYX-2925 PO QD for 2 weeks (2x)&#xD;
&#xD;
        -  Follow-up for 1 week&#xD;
&#xD;
      Eligible subjects will receive MRIs during the screening period, during the placebo period,&#xD;
      during the NYX-2925 PO QD period. Safety assessments will be conducted and adverse events&#xD;
      will be collected during the study. Daily pain scores and other fibromyalgia scales will be&#xD;
      collected during the study. Daily pain scores and other fibromyalgia scales will be collected&#xD;
      for exploratory analysis. During the follow-up period, an optional MRI will be completed for&#xD;
      consenting subjects in order to evaluate duration of effect.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 14, 2017</start_date>
  <completion_date type="Actual">April 18, 2019</completion_date>
  <primary_completion_date type="Actual">April 18, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <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.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <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.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>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.</measure>
    <time_frame>Week 2, Week 4, Week 6</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>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.</measure>
    <time_frame>Week 2, Week 4, and Week 6</time_frame>
  </primary_outcome>
  <other_outcome>
    <measure>Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours</measure>
    <time_frame>Change from Baseline, Week 2 (Placebo), Week 4, and Week 6 (NYX-2925)</time_frame>
    <description>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.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Fibromyalgia</condition>
  <arm_group>
    <arm_group_label>All subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NYX-2925</intervention_name>
    <description>NYX-2925 is a novel small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).</description>
    <arm_group_label>All subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Matching placebo capsules.</description>
    <arm_group_label>All subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects meets the 2010 American College of Rheumatology (ACR) criteria for&#xD;
             fibromyalgia.&#xD;
&#xD;
          2. Self-reported clinical pain ≥ 4 and on the Numeric Pain Rating Scale (NPRS) at&#xD;
             screening and baseline.&#xD;
&#xD;
          3. Subject receives and agrees to remain on their stable fibromyalgia treatment plan&#xD;
             established at least 14 days prior to dosing.&#xD;
&#xD;
          4. Subject agrees to use only non-steroidal anti-inflammatory (NSAID) or acetaminophen&#xD;
             treatment as needed for breakthrough pain, and/or, zopiclone, zolpidem, zaleplon, or&#xD;
             eszopiclone for sleep (if needed).&#xD;
&#xD;
          5. Right handed.&#xD;
&#xD;
          6. Calculates creatinine clearance ≥ 60 mL/minute.&#xD;
&#xD;
          7. Female subjects of child bearing potential with a negative serum pregnancy test prior&#xD;
             to entry into the study and who are practicing an adequate method of birth control&#xD;
             (e.g., surgical sterilization, oral or parenteral contraceptives, intrauterine device&#xD;
             that is considered safe for MRI procedures, barrier [condom with spermicide]) and who&#xD;
             do not plan to become pregnant, breastfeed, or donate ova during the course of the&#xD;
             study and for 28 days after the final administration of investigational product.&#xD;
&#xD;
          8. Ability to understand the requirements of the study, provide written informed consent,&#xD;
             abide by the study restrictions, and agree to return for the required assessments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current or expected use of opioid or narcotic analgesics, monoamine oxidase inhibitors&#xD;
             (MAOIs), tricyclic antidepressants, gabapentins, topiramate, anticonvulsants,&#xD;
             benzodiazepines, and sedatives, or hypnotics.&#xD;
&#xD;
          2. Unstable doses of allowed antidepressants or muscle relaxants. Use of NSAIDs or&#xD;
             acetaminophen 24 hours prior to imaging procedures is prohibited.&#xD;
&#xD;
          3. Pain due to concurrent disease such as rheumatoid arthritis, systemic lupus&#xD;
             erythematosus, inflammatory bowel disease, or other chronic widespread pain&#xD;
             condition(s) that may confound fibromyalgia pain.&#xD;
&#xD;
          4. Untreated endocrine disorder that may confound fibromyalgia assessments.&#xD;
&#xD;
          5. Psychiatric or cognitive disorder (e.g., current schizophrenia, severe depression,&#xD;
             suicidal ideation, dementia, etc.).&#xD;
&#xD;
          6. Clinically significant alcohol or other substance abuse within the last 2 years.&#xD;
&#xD;
          7. Positive screen for medically inappropriate or illegal use of drugs of abuse.&#xD;
&#xD;
          8. Current treatment with medications such as ketamine, amantadine, dextromethorphan,&#xD;
             memantine, methadone, dextropropoxyphene, or ketobemidone.&#xD;
&#xD;
          9. History of allergy, sensitivity, or intolerance to medications such as ketamine,&#xD;
             amantadine, dextromethorphan, memantine, methadone, dextropropoxyphene, or&#xD;
             ketobemidone.&#xD;
&#xD;
         10. Women, who are pregnant, breast feeding, or planning to become pregnant or donate ova&#xD;
             during the course of the study and for 28 days after the final administration of&#xD;
             investigational product.&#xD;
&#xD;
         11. Huntington's, Parkinson's, Alzheimer's, Multiple Sclerosis, or history of seizures,&#xD;
             epilepsy, or strokes.&#xD;
&#xD;
         12. Contraindications to fMRI procedures. These may include but are not limited to:&#xD;
             surgical clips, surgical staples, metal implants, and certain metallic dental&#xD;
             material.&#xD;
&#xD;
         13. Current or habitual use (within the last 12 months) of artificial nails, nails&#xD;
             enhancements, or nail extensions that cover any portion of either thumbnail.&#xD;
&#xD;
         14. Abnormal laboratory results, medical history, or concurrent conditions that would&#xD;
             preclude safe study participation, or interfere with study procedures/assessments.&#xD;
&#xD;
         15. Impaired liver function.&#xD;
&#xD;
         16. Known history of significant heart condition or high blood pressure.&#xD;
&#xD;
         17. Current evidence of dysplasia or history of cancer malignancy (including lymphoma and&#xD;
             leukemia) in the last 5 years.&#xD;
&#xD;
         18. Human immunodeficiency virus (HIV) infection, hepatitis, or other ongoing infectious&#xD;
             disease.&#xD;
&#xD;
         19. History of severe kidney or liver impairment.&#xD;
&#xD;
         20. History of migraine.&#xD;
&#xD;
         21. History of lower limb vascular surgery or current lower limb vascular dysfunction.&#xD;
&#xD;
         22. Received an investigational drug or device within 30 days of dosing.&#xD;
&#xD;
         23. Previous treatment with NYX-2925.&#xD;
&#xD;
         24. Resting heart rate &lt; 45 or ≥ 95 beats per minute.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Aptinyx Clinical Site</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aptinyx Clinical Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <results_first_submitted>October 3, 2021</results_first_submitted>
  <results_first_submitted_qc>August 23, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 16, 2022</results_first_posted>
  <last_update_submitted>August 23, 2022</last_update_submitted>
  <last_update_submitted_qc>August 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fibromyalgia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibromyalgia</mesh_term>
    <mesh_term>Myofascial Pain Syndromes</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 7, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT03249103/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 26, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT03249103/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Approximately 24 subjects were planned to be enrolled. Twenty-two (22) subjects were enrolled.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Treated Subjects</title>
          <description>Subjects received Placebo, 20 mg NYX-2925 once daily (QD), and 200 mg NYX-2925 QD</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Treated Subjects</title>
          <description>Subjects received Placebo, 20 mg NYX-2925 QD, and 200 mg NYX-2925 QD</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="22"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="47.3" spread="15.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fibromyalgia disease history, years</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14.57" spread="14.476"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>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.</title>
        <time_frame>Week 2, Week 4, Week 6</time_frame>
        <population>Population includes study subjects with analyzable images (n=20)</population>
        <group_list>
          <group group_id="O1">
            <title>All Treated Subjects</title>
            <description>Subjects received Placebo, 20 mg NYX-2925 QD, and 200 mg NYX-2925 QD</description>
          </group>
        </group_list>
        <measure>
          <title>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.</title>
          <population>Population includes study subjects with analyzable images (n=20)</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>dACC mean placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1670" spread="0.17796"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>dACC mean NYX-2925 20 mg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0550" spread="0.19710"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>dACC NYX-2925 200 mg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0975" spread="0.19141"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>placebo - NYX-2925 20 mg</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.032</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>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.</title>
        <time_frame>Week 2, Week 4, and Week 6</time_frame>
        <population>Population includes study subjects with analyzable images (n=19)</population>
        <group_list>
          <group group_id="O1">
            <title>All Treated Subjects</title>
            <description>Subjects received Placebo, 20 mg NYX-2925 QD, and 200 mg NYX-2925 QD</description>
          </group>
        </group_list>
        <measure>
          <title>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.</title>
          <population>Population includes study subjects with analyzable images (n=19)</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>pINS mean placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.993" spread="0.13981"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>pINS mean NYX-2925 20 mg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.911" spread="0.14242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>pINS NYX-2925 200 mg</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.903" spread="0.16194"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>placebo - NYX-2925 200 mg</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.039</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours</title>
        <description>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.</description>
        <time_frame>Change from Baseline, Week 2 (Placebo), Week 4, and Week 6 (NYX-2925)</time_frame>
        <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.</population>
        <group_list>
          <group group_id="O1">
            <title>All Treated Subjects</title>
            <description>Subjects received Placebo, 20 mg NYX-2925 QD, and 200 mg NYX-2925 QD</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours</title>
          <description>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.</description>
          <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.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.32" spread="1.411"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.82" spread="1.275"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.74" spread="1.360"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.12" spread="1.650"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0072</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>comparing Week 2 (Placebo) to Week 6 (NYX-2925 200 mg)</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_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).</time_frame>
      <desc>Adverse Events were collected and are summarized for all NYX-2925 exposure. Adverse events were not collected with regard to specific dose.</desc>
      <group_list>
        <group group_id="E1">
          <title>All Treated Subjects</title>
          <description>Subjects received Placebo, 20 mg NYX-2925 QD, and 200 mg NYX-2925 QD. Adverse Events were collected and are summarized for all NYX-2925 exposure. Adverse events were not collected with regard to specific dose.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Diarrhoea/</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Eructation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Tension headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Aptinyx Clinical Development</name_or_title>
      <organization>Aptinyx</organization>
      <phone>847-871-0377 ext 1</phone>
      <email>clinicalstudies@aptinyx.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03249103
org study id: NYX-2925-2002
nct id: NCT03249103
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
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.
primary purpose: Treatment
masking: None (Open Label)
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.
measure: 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
measure: 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
measure: Mean Change in Numeric Pain Rating Scale (NPRS) Score Assessing Average Pain in the Past 24 Hours
time frame: Change from Baseline, Week 2 (Placebo), Week 4, and Week 6 (NYX-2925)
description: 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.
arm group label: All subjects
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: NYX-2925
description: NYX-2925 is a novel small molecule that modulates the N-methyl-D-aspartate receptor (NMDAR).
arm group label: All subjects
intervention type: Drug
intervention name: Placebo oral capsule
description: Matching placebo capsules.
arm group label: All subjects
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fibromyalgia
mesh term: Myofascial Pain Syndromes
sharing ipd: Yes
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 