<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/NCT03774836</url>
  </required_header>
  <id_info>
    <org_study_id>AVE-901-103</org_study_id>
    <nct_id>NCT03774836</nct_id>
  </id_info>
  <brief_title>Tramadol Versus Placebo and Morphine in the Management of Post-Operative Pain Abdominoplasty</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 and Morphine in the Management of Postoperative Pain Following Abdominoplasty</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>
      This study is evaluating the analgesic efficacy of intravenous (IV) tramadol (AVE-901)&#xD;
      compared to placebo in the management of postoperative pain following abdominal surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      (Non-clinical summary) Tramadol is a centrally-acting synthetic analgesic of the&#xD;
      aminocyclohexanol group with opioid-like effects. Tramadol is extensively metabolized&#xD;
      following administration, which results in a number of enantiomeric metabolites that display&#xD;
      different opioid-receptor binding properties, and monoaminergic reuptake inhibition.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 14, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2019</completion_date>
  <primary_completion_date type="Anticipated">May 30, 2019</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 through 24 hours</measure>
    <time_frame>24 hours post dose</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">360</enrollment>
  <condition>Pain Management</condition>
  <arm_group>
    <arm_group_label>Tramadol 50 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Morphine 4 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tramadol</intervention_name>
    <description>IV Tramadol 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
    <arm_group_label>Tramadol 50 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>Morphine 4 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44</description>
    <arm_group_label>Morphine 4 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>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>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patient is male or female 18-75 years of age&#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 contraption&#xD;
&#xD;
          -  The patient must be willing to be housed in a healthcare facility and able to receive&#xD;
             parenteral analgesia for at least 48 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;
          -  The patient is undergoing an abdominoplasty of significant complexity defined as&#xD;
             pre-planned surgical time of greater than 180 mins.&#xD;
&#xD;
          -  The patient has a recent (within 5 years) and/or current history of chronic analgesic,&#xD;
             opiate or tranquilizer abuse or dependence or is a user of illicit drugs or has had a&#xD;
             recent history (within 2 years) of drug or alcohol abuse.&#xD;
&#xD;
          -  The patient is taking herbal or dietary supplements or medications that are moderate&#xD;
             or strong inhibitors of CYP2D6 or CYP3A4 (e.g., fluoxetine, paroxetine, amitriptyline,&#xD;
             quinidine, ketoconazole, erythromycin, grapefruit juice) or inducers of CYP3A4 (e.g.,&#xD;
             carbamazepine, rifampin, St. John's Wort) and cannot go through a minimum washout&#xD;
             period of 14 days prior to surgery.&#xD;
&#xD;
          -  The patient has a history of epilepsy, is susceptible to seizures.&#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, cyclobenzaprine triptans).&#xD;
&#xD;
          -  The patient has had a recent cardiovascular event or clinically significant abnormal&#xD;
             ECG finding at screening or baseline.&#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 CPAP or other treatment.&#xD;
&#xD;
          -  Female patient is pregnant and/or undergoing a pregnancy-related surgery, or&#xD;
             breastfeeding.&#xD;
&#xD;
          -  The patient has a history of cardiopulmonary, neurological or psychiatric or other&#xD;
             medical condition that may confound the assessments of efficacy or safety.&#xD;
&#xD;
          -  The patient has cirrhosis, moderate or severe hepatic impairment or an alanine&#xD;
             aminotransferase (ALT) or aspartate aminotransferase (AST) value &gt; 3X upper limit of&#xD;
             normal (ULN) at Screening.&#xD;
&#xD;
          -  The patient has severe renal impairment or a serum creatinine value of &gt; 2.0 mg/dL at&#xD;
             Screening.&#xD;
&#xD;
          -  The patient has potassium, sodium, calcium or magnesium levels outside of the normal&#xD;
             range or any other clinically significant abnormalities in laboratory values at&#xD;
             Screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <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>Hermann Drive Research</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Endeavor Clinical Trials</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>February 2019</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>May 7, 2019</last_update_submitted>
  <last_update_submitted_qc>May 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Tramadol</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>February 16, 2021</submitted>
    <returned>March 2, 2021</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03774836
org study id: AVE-901-103
nct id: NCT03774836
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is evaluating the analgesic efficacy of intravenous (IV) tramadol (AVE-901)
      compared to placebo in the management of postoperative pain following abdominal surgery.
(Non-clinical summary) Tramadol is a centrally-acting synthetic analgesic of the
      aminocyclohexanol group with opioid-like 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 through 24 hours
time frame: 24 hours post dose
arm group label: Tramadol 50 mg
arm group type: Active Comparator
description: Given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
arm group label: Morphine 4 mg
arm group type: Active Comparator
description: Given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
arm group label: Placebo
arm group type: Placebo Comparator
description: Given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
intervention type: Drug
intervention name: Tramadol
description: IV Tramadol 50 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
arm group label: Tramadol 50 mg
intervention type: Drug
intervention name: Morphine
description: Morphine 4 mg, given at Hours 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44
arm group label: Morphine 4 mg
intervention type: Other
intervention name: Placebo
description: 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: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Morphine
mesh term: Tramadol
submitted: February 16, 2021
returned: March 2, 2021