<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/NCT03290378</url>
  </required_header>
  <id_info>
    <org_study_id>AVE-901-102</org_study_id>
    <nct_id>NCT03290378</nct_id>
  </id_info>
  <brief_title>Tramadol Versus Placebo in the Management of Postoperative Pain Following Bunionectomy</brief_title>
  <official_title>A Phase 3, Multicenter, Randomized, Double Blind, Three-Arm Study to Evaluate the Efficacy and Safety of Tramadol Infusion (AVE-901) Versus Placebo in the Management of Postoperative Pain Following Bunionectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Avenue Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Avenue Therapeutics, Inc.</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 study evaluates the effectiveness and safety of IV tramadol compared to placebo managing&#xD;
      postoperative pain following a bunionectomy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      (Non-clinical summary)&#xD;
&#xD;
      Tramadol is a centrally-acting synthetic analgesic of the aminocyclohexanol group with&#xD;
      opioidlike effects. Tramadol is extensively metabolized following administration, which&#xD;
      results in a number of enantiomeric metabolites that display different opioid-receptor&#xD;
      binding properties, and monoaminergic reuptake inhibition.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 19, 2017</start_date>
  <completion_date type="Actual">April 23, 2018</completion_date>
  <primary_completion_date type="Actual">April 11, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Sum of Pain Intensity Differences (SPID) Through 48 Hours Post First Dose</measure>
    <time_frame>48 hours post first dose</time_frame>
    <description>Pain intensity was recorded using the Numerical Pain Rating Scale (NPRS) from 0 to 10, where 0 was no pain and 10 was the worst pain imaginable at hrs: .5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48. As higher pain scores indicate worse pain, a negative Pain Intensity Difference (PID) indicates less pain (improvement from baseline). Thus, SPID scores are expected to be negative if a patient's pain decreases over time, with the lower SPID values indicating greater reduction in pain intensity.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">409</enrollment>
  <condition>Pain Management</condition>
  <arm_group>
    <arm_group_label>AVE-901 50 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>AVE-901 25 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tramadol</intervention_name>
    <description>IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
    <arm_group_label>AVE-901 25 mg</arm_group_label>
    <arm_group_label>AVE-901 50 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  The patient is male or female 18-75 years of age undergoing unilateral first&#xD;
             metatarsal bunionectomy surgery&#xD;
&#xD;
          -  Willing to give consent and able to understand the study procedures&#xD;
&#xD;
          -  Female patients must be of non-childbearing potential or be practicing a highly&#xD;
             effective contraception&#xD;
&#xD;
          -  The patient must be willing to be housed in a healthcare facility and able to receive&#xD;
             parenteral analgesia for at least 72 hours after surgery.&#xD;
&#xD;
          -  The patient meets definition of American Society of Anesthesiologists (ASA) Physical&#xD;
             Class 1, or 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient is not expected to receive a continuous infusion nerve block as described in&#xD;
             the Post-Op anesthetic procedures protocol&#xD;
&#xD;
          -  Patient is undergoing bilateral or revision bunionectomy surgery&#xD;
&#xD;
          -  The patient has allergy or hypersensitivity (or is intolerant) to opioids or tramadol&#xD;
             The patient has known physical dependence on opioids&#xD;
&#xD;
          -  The patient has taken other prior/concurrent chronic medications that have not been at&#xD;
             a stable dose for at least 2 weeks prior to screening&#xD;
&#xD;
          -  The patient is taking herbal or dietary supplements or medications that are moderate&#xD;
             or strong inhibitors of CYP2D6 or CYP3A4 or inducers of CYP3A4&#xD;
&#xD;
          -  The patient has taken monoamine oxidase (MAO) inhibitors, trazodone, or&#xD;
             cyclobenzaprine within 14 days prior to surgery&#xD;
&#xD;
          -  The patient cannot be withdrawn from medications (at least 7 days prior to surgery)&#xD;
             that may lower the seizure threshold (e.g. anti-psychotic agents, MAOI inhibitors) or&#xD;
             which increase serotonergic tone (e.g. selective serotonin reuptake inhibitors&#xD;
             (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic&#xD;
             antidepressants, triptans).&#xD;
&#xD;
          -  The patient has a history of epilepsy, or is known to be susceptible to seizures&#xD;
&#xD;
          -  The patient has a history of Long QT Syndrome or a relative with this condition&#xD;
&#xD;
          -  The patient has expressed suicidal ideation or is considered to be at risk of suicide.&#xD;
&#xD;
          -  The patient is morbidly obese (body mass index [BMI] ≥ 40 kg/m2) or has documented&#xD;
             sleep apnea requiring pharmacological or device intervention.&#xD;
&#xD;
          -  Clinically significant abnormalities in the judgement of the Investigator&#xD;
&#xD;
          -  The patient was administered an investigational product within 30 days prior to&#xD;
             Screening.&#xD;
&#xD;
          -  The patient has previously participated in a clinical study with AVE-901.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Trovare Clinical Research</name>
      <address>
        <city>Bakersfield</city>
        <state>California</state>
        <zip>93301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lotus Clinical Research</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cheseapeake Research Group, LLC</name>
      <address>
        <city>Pasadena</city>
        <state>Maryland</state>
        <zip>21122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H.D. Research Corporation</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Endeavor Clinical Trials, PA</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 21, 2017</study_first_posted>
  <results_first_submitted>May 10, 2019</results_first_submitted>
  <results_first_submitted_qc>March 11, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 19, 2020</results_first_posted>
  <last_update_submitted>March 11, 2020</last_update_submitted>
  <last_update_submitted_qc>March 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tramadol</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 24, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/78/NCT03290378/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>AVE-901 50 mg</title>
          <description>Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
        </group>
        <group group_id="P2">
          <title>AVE-901 25 mg</title>
          <description>Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Placebo: IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="140"/>
                <participants group_id="P2" count="133"/>
                <participants group_id="P3" count="136"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="137"/>
                <participants group_id="P2" count="123"/>
                <participants group_id="P3" count="120"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="16"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patient 03-042 was randomized to tramadol 25 mg but received tramadol 50 mg in error.</population>
      <group_list>
        <group group_id="B1">
          <title>AVE-901 50 mg</title>
          <description>Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
        </group>
        <group group_id="B2">
          <title>AVE-901 25 mg</title>
          <description>Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Placebo: IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="139"/>
            <count group_id="B2" value="134"/>
            <count group_id="B3" value="136"/>
            <count group_id="B4" value="409"/>
          </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="45.3" spread="13.51"/>
                    <measurement group_id="B2" value="44.5" spread="13.15"/>
                    <measurement group_id="B3" value="45.0" spread="13.44"/>
                    <measurement group_id="B4" value="45.2" spread="13.35"/>
                  </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="120"/>
                    <measurement group_id="B2" value="116"/>
                    <measurement group_id="B3" value="113"/>
                    <measurement group_id="B4" value="349"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="60"/>
                  </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="51"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="52"/>
                    <measurement group_id="B4" value="149"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="88"/>
                    <measurement group_id="B2" value="88"/>
                    <measurement group_id="B3" value="84"/>
                    <measurement group_id="B4" value="260"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" 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="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="37"/>
                    <measurement group_id="B4" value="104"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="104"/>
                    <measurement group_id="B2" value="88"/>
                    <measurement group_id="B3" value="88"/>
                    <measurement group_id="B4" value="280"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="139"/>
                    <measurement group_id="B2" value="134"/>
                    <measurement group_id="B3" value="136"/>
                    <measurement group_id="B4" value="409"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Previous opioid history</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="47"/>
                    <measurement group_id="B4" value="141"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="97"/>
                    <measurement group_id="B2" value="82"/>
                    <measurement group_id="B3" value="89"/>
                    <measurement group_id="B4" value="268"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>American Society of Anesthesiology (ASA) Physical Classification</title>
          <description>Patient was to meet definition of American Society of Anesthesiologists (ASA) Physical Class of I or II:&#xD;
ASA I) normal healthy patient: healthy, non-smoking, no or minimal alcohol use) or&#xD;
ASA II) A patient with mild systemic disease: Mild diseases only without substantive functional limitations. Examples include (but not limited to): current smoker, social alcohol drinker, pregnancy, obesity (30&lt;BMI&lt;40), well-controlled DM/HTN, mild lug disease.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="71"/>
                    <measurement group_id="B3" value="72"/>
                    <measurement group_id="B4" value="213"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="69"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="64"/>
                    <measurement group_id="B4" value="196"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Qualifying Categorical Pain Score</title>
          <description>The patient reported a score of moderate or severe on a 4-point categorical rating scale (with categories of none, mild, moderate, or severe)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="B1" value="89"/>
                    <measurement group_id="B2" value="80"/>
                    <measurement group_id="B3" value="75"/>
                    <measurement group_id="B4" value="244"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="54"/>
                    <measurement group_id="B3" value="61"/>
                    <measurement group_id="B4" value="165"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <description>BMI Calculation: Sites used the NIH website BMI calculator: https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm</description>
          <units>kg/m2</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.9" spread="4.97"/>
                    <measurement group_id="B2" value="28.1" spread="5.48"/>
                    <measurement group_id="B3" value="28.3" spread="4.91"/>
                    <measurement group_id="B4" value="28.1" spread="5.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Qualifying Numerical Pain Rating Scale (NPRS)</title>
          <description>Patient recorded a pain score ≥5, within 8 hours after removal of popliteal block, on an Numerical Pain Rating Scale (NPRS) where 0 is no pain and 10 is the worst pain imaginable. Patient needed to have a pain score of ≥5 to qualify for the study.&#xD;
Mean pain score per treatment group noted below.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.7" spread="1.66"/>
                    <measurement group_id="B2" value="6.8" spread="1.39"/>
                    <measurement group_id="B3" value="6.9" spread="1.63"/>
                    <measurement group_id="B4" value="6.8" spread="1.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Sum of Pain Intensity Differences (SPID) Through 48 Hours Post First Dose</title>
        <description>Pain intensity was recorded using the Numerical Pain Rating Scale (NPRS) from 0 to 10, where 0 was no pain and 10 was the worst pain imaginable at hrs: .5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48. As higher pain scores indicate worse pain, a negative Pain Intensity Difference (PID) indicates less pain (improvement from baseline). Thus, SPID scores are expected to be negative if a patient's pain decreases over time, with the lower SPID values indicating greater reduction in pain intensity.</description>
        <time_frame>48 hours post first dose</time_frame>
        <population>One patient was randomized to tramadol 25 mg but received tramadol 50 mg in error.</population>
        <group_list>
          <group group_id="O1">
            <title>AVE-901 50 mg</title>
            <description>Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
          </group>
          <group group_id="O2">
            <title>AVE-901 25 mg</title>
            <description>Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo: IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
          </group>
        </group_list>
        <measure>
          <title>The Sum of Pain Intensity Differences (SPID) Through 48 Hours Post First Dose</title>
          <description>Pain intensity was recorded using the Numerical Pain Rating Scale (NPRS) from 0 to 10, where 0 was no pain and 10 was the worst pain imaginable at hrs: .5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48. As higher pain scores indicate worse pain, a negative Pain Intensity Difference (PID) indicates less pain (improvement from baseline). Thus, SPID scores are expected to be negative if a patient's pain decreases over time, with the lower SPID values indicating greater reduction in pain intensity.</description>
          <population>One patient was randomized to tramadol 25 mg but received tramadol 50 mg in error.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="139"/>
                <count group_id="O2" value="134"/>
                <count group_id="O3" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-122.8" lower_limit="-135.14" upper_limit="-110.50"/>
                    <measurement group_id="O2" value="-110.9" lower_limit="-123.64" upper_limit="-98.17"/>
                    <measurement group_id="O3" value="-97.8" lower_limit="-110.60" upper_limit="-85.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;.005</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>AVE-901 50 mg</title>
          <description>Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
        </group>
        <group group_id="E2">
          <title>AVE-901 25 mg</title>
          <description>Tramadol: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Placebo: IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="140"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="136"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="136"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</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="93" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="56" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="60" subjects_at_risk="136"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Pruritus generalized</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="136"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Infusion Site Pain</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="136"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>Muscle Twitching</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="136"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="140"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="133"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="136"/>
              </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>VP of Clinical Operations and Program Management</name_or_title>
      <organization>Avenue Therapeutics</organization>
      <phone>781-652-4514</phone>
      <email>mryan@avenuetx.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/NCT03290378
org study id: AVE-901-102
nct id: NCT03290378
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The study evaluates the effectiveness and safety of IV tramadol compared to placebo managing
      postoperative pain following a bunionectomy
(Non-clinical summary)

      Tramadol is a centrally-acting synthetic analgesic of the aminocyclohexanol group with
      opioidlike effects. Tramadol is extensively metabolized following administration, which
      results in a number of enantiomeric metabolites that display different opioid-receptor
      binding properties, and monoaminergic reuptake inhibition.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: The Sum of Pain Intensity Differences (SPID) Through 48 Hours Post First Dose
time frame: 48 hours post first dose
description: Pain intensity was recorded using the Numerical Pain Rating Scale (NPRS) from 0 to 10, where 0 was no pain and 10 was the worst pain imaginable at hrs: .5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48. As higher pain scores indicate worse pain, a negative Pain Intensity Difference (PID) indicates less pain (improvement from baseline). Thus, SPID scores are expected to be negative if a patient's pain decreases over time, with the lower SPID values indicating greater reduction in pain intensity.
arm group label: AVE-901 50 mg
arm group type: Active Comparator
arm group label: AVE-901 25 mg
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Tramadol
description: IV; 25 mg or 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
arm group label: AVE-901 25 mg
arm group label: AVE-901 50 mg
intervention type: Other
intervention name: Placebo
description: IV; Placebo, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Tramadol
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 