xml: <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/NCT05995912</url>
    </required_header>
    <id_info>
      <org_study_id>LT-04-20</org_study_id>
      <secondary_id>LT-04-20</secondary_id>
      <nct_id>NCT05995912</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of Etoricoxib-tramadol Tablet in Acute Postoperative Pain</brief_title>
    <official_title>Efficacy and Safety of Etoricoxib-tramadol 120mg/100mg on Acute Pain After Impacted Lower Third Molar Extraction: A Double Blind Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Laboratorios Liomont</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Infinite Clinical Research, S.A. de C.V.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Laboratorios Liomont</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of the present phase IIb clinical trial was to compare the safety and efficacy of&#xD;
        the fixed-dose combination etoricoxib-tramadol 120mg/100mg tablet (once a day, for three&#xD;
        days) versus naproxen 220mg tablet plus tramadol 50 mg capsule in patients with acute&#xD;
        postoperative pain after impacted third molar extraction. The main research question was: Is&#xD;
        the analgesic efficacy of etoricoxib-tramadol 120mg/100mg tablet non-inferior to naproxen 220&#xD;
        mg tablet + tramadol 50 mg capsule in a clinical model of moderate to severe acute pain?&#xD;
        After informed consent, patients were randomly assigned to one of the two arms: test product&#xD;
        (etoricoxib-tramadol 120mg/100mg tablet) or active comparator (naproxen 220mg tablet +&#xD;
        tramadol 50 mg capsule). After surgery, patients were requested to start the treatment with&#xD;
        study drugs (test product was administered once daily for three days; meanwhile reference&#xD;
        drug was administered twice a day for three days).&#xD;
  &#xD;
        Investigators compared the effects of both treatments on pain intensity at different time&#xD;
        frames using the visual analogue scale. Furthermore, the safety of investigational drugs was&#xD;
        assessed during the study.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">September 29, 2021</start_date>
    <completion_date type="Actual">August 29, 2022</completion_date>
    <primary_completion_date type="Actual">May 23, 2022</primary_completion_date>
    <phase>Phase 2</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>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Pain intensity difference (PID)</measure>
      <time_frame>At 4 h (Day 0, postdosing) respect the baseline (Day 0, before dosing)</time_frame>
      <description>The difference in pain intensity at 4 h after drug administration versus time 0 (baseline, before dosing)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pain intensity difference (PID)</measure>
      <time_frame>At 1, 2, 3, 6, 12, 24, 48, and 72 hours postdosing respecto the baseline (Day 0, before dosing)</time_frame>
      <description>The difference in pain intensity at 1, 2, 3, 6, 12, 24, 48, and 72 hours after drug administration versus time 0 (baseline, before dosing)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total pain relief (TOTPAR)</measure>
      <time_frame>At 4, 6, 12, 24, 48, 72 hours postdosing respect to the baseline (Day 0, before dosing)</time_frame>
      <description>TOTPAR is a time-weighted measure of AUC or total area under the pain relief curve and is a summary measure that integrates serial assessments of a subject's pain over the duration of the study or in any time frime.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Trismus control</measure>
      <time_frame>At the end of the study (Day 7) respect to the baseline (Day 0, before dosing)</time_frame>
      <description>Measurement the difference of mouth opening (in mm) at baseline (before dosing) and at the end of the study (Day 7).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events</measure>
      <time_frame>From informed consent (Day -28) to the end of the study (Day 7)</time_frame>
      <description>Characteristics and frequency of adverse events</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Actual">58</enrollment>
    <condition>Acute Pain</condition>
    <condition>Postoperative Pain</condition>
    <arm_group>
      <arm_group_label>Etoricoxib-Tramadol</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Etoricoxib-Tramadol 120mg/100mg tablet, once-daily, for 3 days</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Naproxen + Tramadol</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Naproxen 220 mg tablet + Tramadol 50 mg capsule, twice a day, for 3 days.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>etoricoxib-tramadol</intervention_name>
      <description>Oral administration (with or without food)</description>
      <arm_group_label>Etoricoxib-Tramadol</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Naproxen</intervention_name>
      <description>Oral administration (with or without food)</description>
      <arm_group_label>Naproxen + Tramadol</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tramadol</intervention_name>
      <description>Oral administration (with or without food)</description>
      <arm_group_label>Naproxen + Tramadol</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients of both sexes aged from 18 to 40 years.&#xD;
  &#xD;
            -  Patients who agreed to participate in the study by signing the informed consent.&#xD;
  &#xD;
            -  Patients with indication for surgical extraction of impacted lower third molars&#xD;
               according to the Pell and Gregory classification.&#xD;
  &#xD;
            -  Healthy subjects or with history of controlled chronic non-communicable diseases or&#xD;
               that can be controlled prior to surgery, which, in the investigator's opinion, do not&#xD;
               represent an additional risk for the patient.&#xD;
  &#xD;
            -  Patients who, at the investigator's discretion, meet personal and family conditions&#xD;
               that allow them to properly comply with the activities described in the protocol and&#xD;
               adherence to treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Findings in the clinical history, vital signs, physical examination or laboratory&#xD;
               studies suggesting abnormal conditions which represent a risk for subject's health at&#xD;
               the investigator´s discretion.&#xD;
  &#xD;
            -  Hypersensitivity to any of the active ingredients and/or excipients of the&#xD;
               investigational drugs.&#xD;
  &#xD;
            -  Patients with active peptic or gastroduodenal ulcer or diagnosis 30 days prior to&#xD;
               signing the informed consent.&#xD;
  &#xD;
            -  Patients with history of allergic asthma reactions.&#xD;
  &#xD;
            -  Patients with severe hepatic dysfunction, classified as Child Pugh C or when being&#xD;
               less, the investigator considers it an additional risk for patients.&#xD;
  &#xD;
            -  Patients with a creatinine clearance &lt;30 mL/min.&#xD;
  &#xD;
            -  Patients with coagulation disorders.&#xD;
  &#xD;
            -  Patients with Systemic Lupus Erythematosus.&#xD;
  &#xD;
            -  Patients with congestive heart failure (NYHA class II-IV), ischemic heart disease,&#xD;
               peripheral arterial disease, or cerebrovascular disease who have recently (3 months)&#xD;
               undergone coronary artery bypass grafting or angioplasty procedures.&#xD;
  &#xD;
            -  Patients at high risk of acute cardiovascular events (intense smoking, hypertension or&#xD;
               uncontrolled diabetes mellitus).&#xD;
  &#xD;
            -  Patients with a history of systemic neoplastic diseases or under treatment with&#xD;
               chemotherapy.&#xD;
  &#xD;
            -  Patients with a history of illicit drug abuse or addiction to alcohol or tobacco.&#xD;
  &#xD;
            -  Patients with monoamine oxidase inhibitors (MAOIs) treatment or during the last 2&#xD;
               weeks prior to the study drug administration.&#xD;
  &#xD;
            -  Patients with opioid analgesics, neuromodulators, or long-acting NSAIDs therapy who,&#xD;
               according to medical criteria, cannot carry out a withdrawal scheme for at least five&#xD;
               half-lives prior to surgery.&#xD;
  &#xD;
            -  Patients with history of seizures or who are under treatment with medications that&#xD;
               reduce the seizure threshold and who, according to medical criteria, cannot carry out&#xD;
               a withdrawal scheme within 30 days prior to surgery.&#xD;
  &#xD;
            -  Positive pregnancy test or lactating women.&#xD;
  &#xD;
            -  Positive rapid urine drug test.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>40 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Tania A. Sibaja Ponce, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Oaxaca Site Management Organization, S.C.</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Oaxaca Site Management Organization</name>
        <address>
          <city>Oaxaca</city>
          <zip>68000</zip>
          <country>Mexico</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Mexico</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Etoricoxib-tramadol</keyword>
    <keyword>Third molar extraction</keyword>
    <keyword>Analgesia</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pain, Postoperative</mesh_term>
      <mesh_term>Acute Pain</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Naproxen</mesh_term>
      <mesh_term>Etoricoxib</mesh_term>
      <mesh_term>Tramadol</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05995912
  org study id: LT-04-20
  secondary id: LT-04-20
  nct id: NCT05995912
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of the present phase IIb clinical trial was to compare the safety and efficacy of
        the fixed-dose combination etoricoxib-tramadol 120mg/100mg tablet (once a day, for three
        days) versus naproxen 220mg tablet plus tramadol 50 mg capsule in patients with acute
        postoperative pain after impacted third molar extraction. The main research question was: Is
        the analgesic efficacy of etoricoxib-tramadol 120mg/100mg tablet non-inferior to naproxen 220
        mg tablet + tramadol 50 mg capsule in a clinical model of moderate to severe acute pain?
        After informed consent, patients were randomly assigned to one of the two arms: test product
        (etoricoxib-tramadol 120mg/100mg tablet) or active comparator (naproxen 220mg tablet +
        tramadol 50 mg capsule). After surgery, patients were requested to start the treatment with
        study drugs (test product was administered once daily for three days; meanwhile reference
        drug was administered twice a day for three days).
  
        Investigators compared the effects of both treatments on pain intensity at different time
        frames using the visual analogue scale. Furthermore, the safety of investigational drugs was
        assessed during the study.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Pain intensity difference (PID)
  time frame: At 4 h (Day 0, postdosing) respect the baseline (Day 0, before dosing)
  description: The difference in pain intensity at 4 h after drug administration versus time 0 (baseline, before dosing)
  measure: Pain intensity difference (PID)
  time frame: At 1, 2, 3, 6, 12, 24, 48, and 72 hours postdosing respecto the baseline (Day 0, before dosing)
  description: The difference in pain intensity at 1, 2, 3, 6, 12, 24, 48, and 72 hours after drug administration versus time 0 (baseline, before dosing)
  measure: Total pain relief (TOTPAR)
  time frame: At 4, 6, 12, 24, 48, 72 hours postdosing respect to the baseline (Day 0, before dosing)
  description: TOTPAR is a time-weighted measure of AUC or total area under the pain relief curve and is a summary measure that integrates serial assessments of a subject's pain over the duration of the study or in any time frime.
  measure: Trismus control
  time frame: At the end of the study (Day 7) respect to the baseline (Day 0, before dosing)
  description: Measurement the difference of mouth opening (in mm) at baseline (before dosing) and at the end of the study (Day 7).
  measure: Adverse events
  time frame: From informed consent (Day -28) to the end of the study (Day 7)
  description: Characteristics and frequency of adverse events
  arm group label: Etoricoxib-Tramadol
  arm group type: Experimental
  description: Etoricoxib-Tramadol 120mg/100mg tablet, once-daily, for 3 days
  arm group label: Naproxen + Tramadol
  arm group type: Active Comparator
  description: Naproxen 220 mg tablet + Tramadol 50 mg capsule, twice a day, for 3 days.
  intervention type: Drug
  intervention name: etoricoxib-tramadol
  description: Oral administration (with or without food)
  arm group label: Etoricoxib-Tramadol
  intervention type: Drug
  intervention name: Naproxen
  description: Oral administration (with or without food)
  arm group label: Naproxen + Tramadol
  intervention type: Drug
  intervention name: Tramadol
  description: Oral administration (with or without food)
  arm group label: Naproxen + Tramadol
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 40 Years
  healthy volunteers: No
  last name: Tania A. Sibaja Ponce, M.D.
  role: Principal Investigator
  affiliation: Oaxaca Site Management Organization, S.C.
  facility: 
  country: Mexico
  responsible party type: Sponsor
  mesh term: Pain, Postoperative
  mesh term: Acute Pain
  mesh term: Naproxen
  mesh term: Etoricoxib
  mesh term: Tramadol
  sharing ipd: Undecided