<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/NCT01728246</url>
  </required_header>
  <id_info>
    <org_study_id>CR013696</org_study_id>
    <secondary_id>TRAMAPNAP4002</secondary_id>
    <nct_id>NCT01728246</nct_id>
  </id_info>
  <brief_title>An Efficacy, Safety and Effects on Quality of Life of Tramadol/Paracetamol as Add-on Therapy in Chronic Osteoarthritis</brief_title>
  <official_title>A Randomized Controlled Trial on the Efficacy, Safety and Quality of Life Effects of Add-on Tramadol/Paracetamol Combination in Chronic Osteoarthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Pharmaceutica</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Pharmaceutica</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy, safety and effects on Quality of Life&#xD;
      (QOL) of tramadol/paracetamol (APAP) as an add-on therapy (medication taken in addition to&#xD;
      another medication) in Filipino participants with chronic (lasting a long time)&#xD;
      osteoarthritis (disorder, which is seen mostly in older persons, in which the joints become&#xD;
      painful and stiff).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label (all people know the identity of the intervention), randomized (study&#xD;
      drug assigned by chance), controlled study to evaluate the efficacy, safety and effects on&#xD;
      QOL of tramadol/APAP as an add-on therapy in Filipino participants suffering from chronic&#xD;
      pain because of chronic osteoarthritis. Participants will be randomly assigned to 2 groups:&#xD;
      tramadol/APAP group and non tramadol/APAP group. Participants in tramadol/APAP group will&#xD;
      receive celecoxib 200 milligram (mg) and fixed dose combination of tramadol (37.5 mg)/APAP&#xD;
      (325 mg) as add on therapy, while the participants in non-tramadol/APAP group will receive&#xD;
      celecoxib 200 mg only. The total duration of the study will be 4 weeks. The participants in&#xD;
      both the groups will be given celecoxib 200 mg once daily for 4 weeks. In addition, the&#xD;
      participants in the tramadol/APAP group will be given add-on tramadol/APAP doses 3 times a&#xD;
      day for 4 weeks. Participants will be asked to return for follow-up at Weeks 2 and 4.&#xD;
      Efficacy will be assessed using 100 millimeter (mm) Visual Analog Scale (VAS) while QOL will&#xD;
      be assessed using the Oswestry Disability Index (ODI). Participant safety will be monitored&#xD;
      throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2007</start_date>
  <completion_date type="Actual">May 2008</completion_date>
  <primary_completion_date type="Actual">May 2008</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>VAS is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in VAS-pain Score at Week 4</measure>
    <time_frame>Baseline and Week 4 Last Observation Carried Forward (LOCF)</time_frame>
    <description>VAS is a 100 mm scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Oswestry Disability Index (ODI) Score at Week 2</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in ODI Score at Week 4</measure>
    <time_frame>Baseline and Week 4 (LOCF)</time_frame>
    <description>The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Who Discontinued Because of Rescue Medication</measure>
    <time_frame>Baseline up to Week 4</time_frame>
    <description>Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Discontinuation Because of Rescue Medication</measure>
    <time_frame>Baseline up to Week 4</time_frame>
    <description>Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">473</enrollment>
  <condition>Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>Tramadol/Paracetamol (APAP)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Tramadol/APAP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tramadol/Paracetamol (APAP)</intervention_name>
    <description>Celecoxib 200 milligram (mg) once daily for 4 weeks and fixed dose combination of Tramadol 37.5 mg/Paracetamol 325 mg thrice daily for 4 weeks as add-on therapy.</description>
    <arm_group_label>Tramadol/Paracetamol (APAP)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Non-Tramadol/APAP</intervention_name>
    <description>Celecoxib 200 mg alone once daily for 4 weeks.</description>
    <arm_group_label>Non-Tramadol/APAP</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with chronic osteoarthritis of knee or hip for greater than (&gt;) or equal to&#xD;
             (=) 1 year (based on the American College of Rheumatology (ACR) diagnostic criteria&#xD;
             for osteoarthritis), who are experiencing at least moderate osteoarthritis pain (&gt;=50&#xD;
             millimeter [mm] in 100 mm Visual Analog Scale [VAS])&#xD;
&#xD;
          -  On any Cyclooxygenase - 2 (COX-2) inhibitors for at least 2 weeks preceding the study&#xD;
&#xD;
          -  Women with childbearing potential must have negative pregnancy test&#xD;
&#xD;
          -  Women of child bearing potential must agree to use accepted methods of contraception&#xD;
&#xD;
          -  Participant has signed the written informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants taking Monoamine oxydase (MAO) inhibitors, neuroleptics or drugs for&#xD;
             seizures&#xD;
&#xD;
          -  Severe hepatic impairment (the impaired ability of the liver to fulfill its role in&#xD;
             metabolism)&#xD;
&#xD;
          -  On maintenance tramadol and/or paracetamol(APAP)&#xD;
&#xD;
          -  On sedative hypnotics, short-acting analgesics, topical medications and anesthetics,&#xD;
             and/or muscle relaxants&#xD;
&#xD;
          -  Pregnant, lactating or breastfeeding participants&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Pharmaceutica Clinical trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Pharmaceutica</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Janssen Philippines</name>
      <address>
        <city>Paranaque City</city>
        <state>Metro Manila</state>
        <zip>1700</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Philippines</country>
  </location_countries>
  <verification_date>February 2013</verification_date>
  <study_first_submitted>November 13, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 19, 2012</study_first_posted>
  <results_first_submitted>December 7, 2012</results_first_submitted>
  <results_first_submitted_qc>December 7, 2012</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 14, 2013</results_first_posted>
  <last_update_submitted>February 6, 2013</last_update_submitted>
  <last_update_submitted_qc>February 6, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 12, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Osteoarthritis</keyword>
  <keyword>Celecoxib</keyword>
  <keyword>Tramadol</keyword>
  <keyword>Paracetamol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Tramadol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Tramadol/Paracetamol (APAP)</title>
          <description>Celecoxib 200 milligram (mg) administered orally once daily for 4 weeks and fixed dose combination of tramadol 37.5 mg/paracetamol 325 mg administered orally thrice daily for 4 weeks as add-on therapy.</description>
        </group>
        <group group_id="P2">
          <title>Non-Tramadol/APAP</title>
          <description>Celecoxib 200 mg administered orally once daily for 4 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="242"/>
                <participants group_id="P2" count="231"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="206"/>
                <participants group_id="P2" count="195"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Participant needed rescue medication</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Tramadol/Paracetamol (APAP)</title>
          <description>Celecoxib 200 milligram (mg) administered orally once daily for 4 weeks and fixed dose combination of tramadol 37.5 mg/paracetamol 325 mg administered orally thrice daily for 4 weeks as add-on therapy.</description>
        </group>
        <group group_id="B2">
          <title>Non-Tramadol/APAP</title>
          <description>Celecoxib 200 mg administered orally once daily for 4 weeks.</description>
        </group>
        <group group_id="B3">
          <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="242"/>
            <count group_id="B2" value="231"/>
            <count group_id="B3" value="473"/>
          </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="61.991" spread="12.084"/>
                    <measurement group_id="B2" value="62.40" spread="12.437"/>
                    <measurement group_id="B3" value="62.19" spread="12.248"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Female</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="171"/>
                    <measurement group_id="B2" value="177"/>
                    <measurement group_id="B3" value="348"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Male</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2</title>
        <description>VAS is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>Intent-to-treat (ITT) population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Tramadol/Paracetamol (APAP)</title>
            <description>Celecoxib 200 milligram (mg) administered orally once daily for 4 weeks and fixed dose combination of tramadol 37.5 mg/paracetamol 325 mg administered orally thrice daily for 4 weeks as add-on therapy.</description>
          </group>
          <group group_id="O2">
            <title>Non-Tramadol/APAP</title>
            <description>Celecoxib 200 mg administered orally once daily for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2</title>
          <description>VAS is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.</description>
          <population>Intent-to-treat (ITT) population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment.</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="242"/>
                <count group_id="O2" value="231"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.86" spread="13.485"/>
                    <measurement group_id="O2" value="68.03" spread="13.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-29.721" spread="16.936"/>
                    <measurement group_id="O2" value="-21.972" spread="12.906"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in VAS-pain Score at Week 4</title>
        <description>VAS is a 100 mm scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.</description>
        <time_frame>Baseline and Week 4 Last Observation Carried Forward (LOCF)</time_frame>
        <population>ITT population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment. LOCF method was used.</population>
        <group_list>
          <group group_id="O1">
            <title>Tramadol/Paracetamol (APAP)</title>
            <description>Celecoxib 200 milligram (mg) administered orally once daily for 4 weeks and fixed dose combination of tramadol 37.5 mg/paracetamol 325 mg administered orally thrice daily for 4 weeks as add-on therapy.</description>
          </group>
          <group group_id="O2">
            <title>Non-Tramadol/APAP</title>
            <description>Celecoxib 200 mg administered orally once daily for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in VAS-pain Score at Week 4</title>
          <description>VAS is a 100 mm scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.</description>
          <population>ITT population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment. LOCF method was used.</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="242"/>
                <count group_id="O2" value="231"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-45.027" spread="19.963"/>
                    <measurement group_id="O2" value="-34.266" spread="15.665"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Oswestry Disability Index (ODI) Score at Week 2</title>
        <description>The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability.</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>Data was not analyzed at Week 2 as time frame was too short to assess Quality of Life (QOL) by ODI score.</population>
        <group_list>
          <group group_id="O1">
            <title>Tramadol/Paracetamol (APAP)</title>
            <description>Celecoxib 200 milligram (mg) administered orally once daily for 4 weeks and fixed dose combination of tramadol 37.5 mg/paracetamol 325 mg administered orally thrice daily for 4 weeks as add-on therapy.</description>
          </group>
          <group group_id="O2">
            <title>Non-Tramadol/APAP</title>
            <description>Celecoxib 200 mg administered orally once daily for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Oswestry Disability Index (ODI) Score at Week 2</title>
          <description>The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability.</description>
          <population>Data was not analyzed at Week 2 as time frame was too short to assess Quality of Life (QOL) by ODI score.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in ODI Score at Week 4</title>
        <description>The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability.</description>
        <time_frame>Baseline and Week 4 (LOCF)</time_frame>
        <population>ITT population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment. LOCF method was used.</population>
        <group_list>
          <group group_id="O1">
            <title>Tramadol/Paracetamol (APAP)</title>
            <description>Celecoxib 200 milligram (mg) administered orally once daily for 4 weeks and fixed dose combination of tramadol 37.5 mg/paracetamol 325 mg administered orally thrice daily for 4 weeks as add-on therapy.</description>
          </group>
          <group group_id="O2">
            <title>Non-Tramadol/APAP</title>
            <description>Celecoxib 200 mg administered orally once daily for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in ODI Score at Week 4</title>
          <description>The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability.</description>
          <population>ITT population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment. LOCF method was used.</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="242"/>
                <count group_id="O2" value="231"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.24" spread="17.034"/>
                    <measurement group_id="O2" value="57.23" spread="16.780"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 4 (LOCF)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.102" spread="15.103"/>
                    <measurement group_id="O2" value="-15.177" spread="13.328"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Discontinued Because of Rescue Medication</title>
        <description>Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation.</description>
        <time_frame>Baseline up to Week 4</time_frame>
        <population>ITT population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Tramadol/Paracetamol (APAP)</title>
            <description>Celecoxib 200 milligram (mg) administered orally once daily for 4 weeks and fixed dose combination of tramadol 37.5 mg/paracetamol 325 mg administered orally thrice daily for 4 weeks as add-on therapy.</description>
          </group>
          <group group_id="O2">
            <title>Non-Tramadol/APAP</title>
            <description>Celecoxib 200 mg administered orally once daily for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Discontinued Because of Rescue Medication</title>
          <description>Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation.</description>
          <population>ITT population included all the participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="242"/>
                <count group_id="O2" value="231"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.41"/>
                    <measurement group_id="O2" value="2.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to Discontinuation Because of Rescue Medication</title>
        <description>Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation.</description>
        <time_frame>Baseline up to Week 4</time_frame>
        <population>Time to discontinuation because of rescue medication was not analyzed, because dates when the rescue medication was given were not properly filled out in the forms, hence the exact time to discontinuation because of rescue medication could not be determined or analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Tramadol/Paracetamol (APAP)</title>
            <description>Celecoxib 200 milligram (mg) administered orally once daily for 4 weeks and fixed dose combination of tramadol 37.5 mg/paracetamol 325 mg administered orally thrice daily for 4 weeks as add-on therapy.</description>
          </group>
          <group group_id="O2">
            <title>Non-Tramadol/APAP</title>
            <description>Celecoxib 200 mg administered orally once daily for 4 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Discontinuation Because of Rescue Medication</title>
          <description>Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation.</description>
          <population>Time to discontinuation because of rescue medication was not analyzed, because dates when the rescue medication was given were not properly filled out in the forms, hence the exact time to discontinuation because of rescue medication could not be determined or analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From signing of informed consent until 30 days after the last dose of study medication</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Tramadol/Paracetamol (APAP)</title>
          <description>Celecoxib 200 milligram (mg) administered orally once daily for 4 weeks and fixed dose combination of tramadol 37.5 mg/paracetamol 325 mg administered orally thrice daily for 4 weeks as add-on therapy.</description>
        </group>
        <group group_id="E2">
          <title>Non-Tramadol/APAP</title>
          <description>Celecoxib 200 mg administered orally once daily for 4 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>No coding system</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Severe Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Generalized Body Rashes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Dizziness / Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Vaginal Bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>No coding system</default_vocab>
        <default_assessment>Non-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="19" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="231"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Drowsiness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Dizziness / Nausea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Increase Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Increase Swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Vomitting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Palpitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Onset of Pain Contralateral to the Reference Point</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Leg Heaviness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Chest Tightening</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="231"/>
              </event>
              <event>
                <sub_title>Sensation of Heat</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="242"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="231"/>
              </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 NOT 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>Medical Affairs Manager</name_or_title>
      <organization>Janssen Pharmaceutica</organization>
      <phone>+632-8247901</phone>
    </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/NCT01728246
org study id: CR013696
secondary id: TRAMAPNAP4002
nct id: NCT01728246
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the efficacy, safety and effects on Quality of Life
      (QOL) of tramadol/paracetamol (APAP) as an add-on therapy (medication taken in addition to
      another medication) in Filipino participants with chronic (lasting a long time)
      osteoarthritis (disorder, which is seen mostly in older persons, in which the joints become
      painful and stiff).
This is an open-label (all people know the identity of the intervention), randomized (study
      drug assigned by chance), controlled study to evaluate the efficacy, safety and effects on
      QOL of tramadol/APAP as an add-on therapy in Filipino participants suffering from chronic
      pain because of chronic osteoarthritis. Participants will be randomly assigned to 2 groups:
      tramadol/APAP group and non tramadol/APAP group. Participants in tramadol/APAP group will
      receive celecoxib 200 milligram (mg) and fixed dose combination of tramadol (37.5 mg)/APAP
      (325 mg) as add on therapy, while the participants in non-tramadol/APAP group will receive
      celecoxib 200 mg only. The total duration of the study will be 4 weeks. The participants in
      both the groups will be given celecoxib 200 mg once daily for 4 weeks. In addition, the
      participants in the tramadol/APAP group will be given add-on tramadol/APAP doses 3 times a
      day for 4 weeks. Participants will be asked to return for follow-up at Weeks 2 and 4.
      Efficacy will be assessed using 100 millimeter (mm) Visual Analog Scale (VAS) while QOL will
      be assessed using the Oswestry Disability Index (ODI). Participant safety will be monitored
      throughout the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) Score at Week 2
time frame: Baseline and Week 2
description: VAS is a 100 millimeter (mm) scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
measure: Change From Baseline in VAS-pain Score at Week 4
time frame: Baseline and Week 4 Last Observation Carried Forward (LOCF)
description: VAS is a 100 mm scale. Intensity of pain range: 0 mm=no pain to 100 mm=worst possible pain. Change=scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
measure: Change From Baseline in Oswestry Disability Index (ODI) Score at Week 2
time frame: Baseline and Week 2
description: The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability.
measure: Change From Baseline in ODI Score at Week 4
time frame: Baseline and Week 4 (LOCF)
description: The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire that is usually completed in less than 5 minutes. The ODI consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). A higher score represents greater disability.
measure: Percentage of Participants Who Discontinued Because of Rescue Medication
time frame: Baseline up to Week 4
description: Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation.
measure: Time to Discontinuation Because of Rescue Medication
time frame: Baseline up to Week 4
description: Rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation.
arm group label: Tramadol/Paracetamol (APAP)
arm group type: Experimental
arm group label: Non-Tramadol/APAP
arm group type: Active Comparator
intervention type: Drug
intervention name: Tramadol/Paracetamol (APAP)
description: Celecoxib 200 milligram (mg) once daily for 4 weeks and fixed dose combination of Tramadol 37.5 mg/Paracetamol 325 mg thrice daily for 4 weeks as add-on therapy.
arm group label: Tramadol/Paracetamol (APAP)
intervention type: Drug
intervention name: Non-Tramadol/APAP
description: Celecoxib 200 mg alone once daily for 4 weeks.
arm group label: Non-Tramadol/APAP
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Janssen Pharmaceutica Clinical trial
role: Study Director
affiliation: Janssen Pharmaceutica
facility: 
country: Philippines
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Acetaminophen
mesh term: Tramadol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 