<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/NCT01716039</url>
  </required_header>
  <id_info>
    <org_study_id>RP1204</org_study_id>
    <nct_id>NCT01716039</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC)</brief_title>
  <official_title>A Study to Evaluate the Pharmacokinetics of Adalimumab in Combination With Methotrexate for the Treatment of Patients With Ulcerative Colitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alimentiv Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Abbott</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Alimentiv Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Assess the body's reaction to dose-response relationship for the adalimumab/Methotrexate&#xD;
      interaction in subjects with moderately to severely active ulcerative colitis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Assess the Pharmacokinetic dose-response relationship for the adalimumab/Methotrexate&#xD;
      interaction in subjects with moderately to severely active UC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Unable to achieve recruitment target.&#xD;
  </why_stopped>
  <start_date>June 2013</start_date>
  <completion_date type="Actual">July 18, 2016</completion_date>
  <primary_completion_date type="Actual">July 18, 2016</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups</measure>
    <time_frame>Baseline up to Week 18</time_frame>
    <description>The modified Baron score is scored on a 0-4 scale that evaluates friability, vascular pattern, bleeding and ulceration on a 5-point grading scale with a higher score indicating more severe disease activity.&#xD;
The mean change and 95% CI are based on least square means from the analysis of covariance</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.</measure>
    <time_frame>Baseline up to Week 18</time_frame>
    <description>UCEIS is a simple scoring tool that contains3 items (vascular pattern, bleeding, and ulceration).&#xD;
The UCEIS scores 3 endoscopic items: vascular pattern (ranges 0-2 points), bleeding (ranges 0-3 points), and the presence of ulcers and erosions (ranges 0-3 points).The total UCEIS is calculated by adding up the 3 item scores(range,0-8points), with higher scores representing more severe disease activity.&#xD;
The mean change and 95% CI are based on least square means from the analysis of covariance</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>MTX 12.5</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Receive once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX and/or placebo in addition to doses of adalimumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MTX 25 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX in addition to doses of adalimumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Once weekly oral dosing with placebo (n=20) two weeks prior to the initiation of adalimumab. Subjects will receive 18 weekly doses of placebo in addition to doses of adalimumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MTX 12.5</intervention_name>
    <description>once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score ≤9 or &gt;9).&#xD;
Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab</description>
    <arm_group_label>MTX 12.5</arm_group_label>
    <other_name>MTX</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MTX 25</intervention_name>
    <description>once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score ≤9 or &gt;9).&#xD;
Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab</description>
    <arm_group_label>MTX 25 mg</arm_group_label>
    <other_name>MTX</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adalimumab</intervention_name>
    <description>Subjects will receive 18 weekly doses of adalimumab</description>
    <arm_group_label>MTX 12.5</arm_group_label>
    <arm_group_label>MTX 25 mg</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Humira</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or non-pregnant, non-lactating females. Females of child bearing potential must&#xD;
             have a negative serum pregnancy test prior to randomization, and must use a hormonal&#xD;
             (oral, implantable or injectable) or barrier method of birth control throughout the&#xD;
             study. Females unable to bear children must have documentation of such in the source&#xD;
             records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum&#xD;
             of one year since the last menstrual period]).&#xD;
&#xD;
          -  Diagnosis of UC confirmed by established criteria, regardless of disease duration.&#xD;
&#xD;
          -  Moderate to severely active UC, defined by a modified Mayo Score ≥6, with confirmed&#xD;
             endoscopic activity by central reader (Mayo endoscopic subscore ≥2).&#xD;
&#xD;
          -  Require initiation with adalimumab for induction of remission.&#xD;
&#xD;
          -  Ability of subject to swallow study drug capsules.&#xD;
&#xD;
          -  Ability of subject to participate fully in all aspects of this clinical trial.&#xD;
&#xD;
          -  Written informed consent must be obtained and documented.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with a TNF antagonist or biological therapy.&#xD;
&#xD;
          -  Prior treatment with MTX.&#xD;
&#xD;
          -  Disease limited to the rectum (proctitis).&#xD;
&#xD;
          -  Documented presence of antibodies against adalimumab.&#xD;
&#xD;
          -  Contraindication for anti-TNF or MTX therapy.&#xD;
&#xD;
          -  Contraindication for endoscopy.&#xD;
&#xD;
          -  Ostomy.&#xD;
&#xD;
          -  Planned surgery.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brian Feagan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Robarts Research Institute - Western University</affiliation>
  </overall_official>
  <reference>
    <citation>Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516. Erratum In: N Engl J Med. 2006 May 18;354(20):2200.</citation>
    <PMID>16339095</PMID>
  </reference>
  <reference>
    <citation>Rutgeerts P, Van Assche G, Sandborn WJ, Wolf DC, Geboes K, Colombel JF, Reinisch W; EXTEND Investigators; Kumar A, Lazar A, Camez A, Lomax KG, Pollack PF, D'Haens G. Adalimumab induces and maintains mucosal healing in patients with Crohn's disease: data from the EXTEND trial. Gastroenterology. 2012 May;142(5):1102-1111.e2. doi: 10.1053/j.gastro.2012.01.035. Epub 2012 Feb 8.</citation>
    <PMID>22326435</PMID>
  </reference>
  <reference>
    <citation>Reinisch W, Sandborn WJ, Hommes DW, D'Haens G, Hanauer S, Schreiber S, Panaccione R, Fedorak RN, Tighe MB, Huang B, Kampman W, Lazar A, Thakkar R. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011 Jun;60(6):780-7. doi: 10.1136/gut.2010.221127. Epub 2011 Jan 5.</citation>
    <PMID>21209123</PMID>
  </reference>
  <reference>
    <citation>Baert F, Noman M, Vermeire S, Van Assche G, D' Haens G, Carbonez A, Rutgeerts P. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003 Feb 13;348(7):601-8. doi: 10.1056/NEJMoa020888.</citation>
    <PMID>12584368</PMID>
  </reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>October 15, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <results_first_submitted>April 26, 2021</results_first_submitted>
  <results_first_submitted_qc>June 1, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 23, 2021</results_first_posted>
  <last_update_submitted>June 1, 2021</last_update_submitted>
  <last_update_submitted_qc>June 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Moderately to severely active Ulcerative Colitis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adalimumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
        </group>
        <group group_id="P2">
          <title>MTX 12.5 mg</title>
          <description>Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
        </group>
        <group group_id="P3">
          <title>MTX 25 mg</title>
          <description>Participants randomized to receive Methotrexate 25.0 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
        </group>
        <group group_id="B2">
          <title>MTX 12.5 mg</title>
          <description>Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab:18 weekly doses of adalimumab</description>
        </group>
        <group group_id="B3">
          <title>MTX 25 mg</title>
          <description>Participants randomized to receive Methotrexate 25.0 mg at Week 00 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab: 18 weekly doses of adalimumab</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="4"/>
            <count group_id="B2" value="8"/>
            <count group_id="B3" value="10"/>
            <count group_id="B4" value="22"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.9" spread="14.6"/>
                    <measurement group_id="B2" value="46.2" spread="13.7"/>
                    <measurement group_id="B3" value="48.5" spread="13.5"/>
                    <measurement group_id="B4" value="46.5" spread="13.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Male</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Female</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease Duration (Years)</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.8" spread="8.0"/>
                    <measurement group_id="B2" value="5.1" spread="3.7"/>
                    <measurement group_id="B3" value="7.0" spread="9.3"/>
                    <measurement group_id="B4" value="7.0" spread="7.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75.0" spread="15.3"/>
                    <measurement group_id="B2" value="75.5" spread="15.2"/>
                    <measurement group_id="B3" value="89.6" spread="20.5"/>
                    <measurement group_id="B4" value="81.8" spread="18.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>C-Reactive protein (CRP)</title>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.6" spread="3.9"/>
                    <measurement group_id="B2" value="5.2" spread="2.7"/>
                    <measurement group_id="B3" value="15.1" spread="16.1"/>
                    <measurement group_id="B4" value="9.9" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fecal Calprotectin</title>
          <units>ug/g</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="606.7" spread="566.6"/>
                    <measurement group_id="B2" value="675.8" spread="431.6"/>
                    <measurement group_id="B3" value="545.2" spread="362.0"/>
                    <measurement group_id="B4" value="603.7" spread="400.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mayo Clinic Score</title>
          <description>The Mayo Clinic Score includes 4 variables: stool frequency, rectal bleeding, a physician's global assessment, and endoscopic findings with flexible sigmoidoscopy. Each variable is scored on a 4-point scale (0-3 points) and summed to give a total disease activity score (maximum score = 12), with higher scores representing more severe disease activity</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.0" spread="1.2"/>
                    <measurement group_id="B2" value="8.6" spread="2.1"/>
                    <measurement group_id="B3" value="8.7" spread="2.1"/>
                    <measurement group_id="B4" value="8.7" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups</title>
        <description>The modified Baron score is scored on a 0-4 scale that evaluates friability, vascular pattern, bleeding and ulceration on a 5-point grading scale with a higher score indicating more severe disease activity.&#xD;
The mean change and 95% CI are based on least square means from the analysis of covariance</description>
        <time_frame>Baseline up to Week 18</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks.&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
          </group>
          <group group_id="O2">
            <title>MTX 12.5mg</title>
            <description>Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks.&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
          </group>
          <group group_id="O3">
            <title>MTX 25 mg</title>
            <description>Participants randomized to receive Methotrexate 25.0 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups</title>
          <description>The modified Baron score is scored on a 0-4 scale that evaluates friability, vascular pattern, bleeding and ulceration on a 5-point grading scale with a higher score indicating more severe disease activity.&#xD;
The mean change and 95% CI are based on least square means from the analysis of covariance</description>
          <units>score 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="4"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="1.2"/>
                    <measurement group_id="O2" value="1.1" spread="1.6"/>
                    <measurement group_id="O3" value="0.9" spread="1.8"/>
                  </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>Other</non_inferiority_type>
            <non_inferiority_desc>Comparing the change in the modified Baron score from baseline to week 18 between the treatment groups</non_inferiority_desc>
            <p_value>0.758</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>1.00</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.</title>
        <description>UCEIS is a simple scoring tool that contains3 items (vascular pattern, bleeding, and ulceration).&#xD;
The UCEIS scores 3 endoscopic items: vascular pattern (ranges 0-2 points), bleeding (ranges 0-3 points), and the presence of ulcers and erosions (ranges 0-3 points).The total UCEIS is calculated by adding up the 3 item scores(range,0-8points), with higher scores representing more severe disease activity.&#xD;
The mean change and 95% CI are based on least square means from the analysis of covariance</description>
        <time_frame>Baseline up to Week 18</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks.&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
          </group>
          <group group_id="O2">
            <title>MTX 12.5 mg</title>
            <description>Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
          </group>
          <group group_id="O3">
            <title>MTX 25 mg</title>
            <description>Participants randomized to receive Methotrexate 25.0 mg at Week 0(two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.</title>
          <description>UCEIS is a simple scoring tool that contains3 items (vascular pattern, bleeding, and ulceration).&#xD;
The UCEIS scores 3 endoscopic items: vascular pattern (ranges 0-2 points), bleeding (ranges 0-3 points), and the presence of ulcers and erosions (ranges 0-3 points).The total UCEIS is calculated by adding up the 3 item scores(range,0-8points), with higher scores representing more severe disease activity.&#xD;
The mean change and 95% CI are based on least square means from the analysis of covariance</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" lower_limit="-2.3" upper_limit="3.4"/>
                    <measurement group_id="O2" value="0.7" lower_limit="-1.0" upper_limit="2.4"/>
                    <measurement group_id="O3" value="1.1" lower_limit="-0.6" upper_limit="2.7"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.908</p_value>
            <p_value_desc>p-value for the overall treatment difference is based on an analysis of covariance adjusting for baseline UCEIS</p_value_desc>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Through study completion, an average of 18 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants randomized to receive placebo at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
        </group>
        <group group_id="E2">
          <title>MTX 12.5 mg</title>
          <description>Participants randomized to receive Methotrexate 12.5 mg at Week 0 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab: 18 weekly doses of adalimumab</description>
        </group>
        <group group_id="E3">
          <title>MTX 25 mg</title>
          <description>Participants randomized to receive Methotrexate 25.0 mg at Week 00 (two weeks prior to the initiation of adalimumab induction therapy) and then every week for 18 weeks&#xD;
Adalimumab:18 weekly doses of adalimumab</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>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="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis ulcerative</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Ocular hyperaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Colitis ulcerative</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Epigastric discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Erythema nodosum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Pallor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </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>The PI of this Investigator-Initiated study had right to prior publication. If PI did not commence publication within 12months after the close of trial at all sites or after PI's manuscript was accepted for publication, whichever occurs first, the Sub-I and Sub-Institution were free to publish or present, provided that the Sub-I provided to the PI any doc. to be submitted for publication at least 30days prior to the planned date of submission for publication to permit a review of the Manuscript.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr.Jenny Jeyarajah (Sr. Biostatistician)</name_or_title>
      <organization>Alimentiv (Formerly Robarts Clinical Trails)</organization>
      <email>jenny.jeyarajah@alimentiv.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/NCT01716039
org study id: RP1204
nct id: NCT01716039
lead sponsor: 
collaborator: 
has dmc: No
Assess the body's reaction to dose-response relationship for the adalimumab/Methotrexate
      interaction in subjects with moderately to severely active ulcerative colitis.
Assess the Pharmacokinetic dose-response relationship for the adalimumab/Methotrexate
      interaction in subjects with moderately to severely active UC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in the Modified Baron Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups
time frame: Baseline up to Week 18
description: The modified Baron score is scored on a 0-4 scale that evaluates friability, vascular pattern, bleeding and ulceration on a 5-point grading scale with a higher score indicating more severe disease activity.
The mean change and 95% CI are based on least square means from the analysis of covariance
measure: Change in the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Score From Baseline to the Final Visit (Week 18) Between the Treatment Groups.
time frame: Baseline up to Week 18
description: UCEIS is a simple scoring tool that contains3 items (vascular pattern, bleeding, and ulceration).
The UCEIS scores 3 endoscopic items: vascular pattern (ranges 0-2 points), bleeding (ranges 0-3 points), and the presence of ulcers and erosions (ranges 0-3 points).The total UCEIS is calculated by adding up the 3 item scores(range,0-8points), with higher scores representing more severe disease activity.
The mean change and 95% CI are based on least square means from the analysis of covariance
arm group label: MTX 12.5
arm group type: Active Comparator
description: Receive once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX and/or placebo in addition to doses of adalimumab
arm group label: MTX 25 mg
arm group type: Active Comparator
description: Once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab 18 weekly doses of MTX in addition to doses of adalimumab
arm group label: Placebo
arm group type: Placebo Comparator
description: Once weekly oral dosing with placebo (n=20) two weeks prior to the initiation of adalimumab. Subjects will receive 18 weekly doses of placebo in addition to doses of adalimumab
intervention type: Drug
intervention name: MTX 12.5
description: once weekly oral dosing with MTX 12.5 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score ≤9 or >9).
Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab
arm group label: MTX 12.5
other name: MTX
intervention type: Drug
intervention name: MTX 25
description: once weekly oral dosing with MTX 25 mg (n=40) two weeks prior to the initiation of adalimumab. Randomization will be stratified by disease activity (modified Mayo Score ≤9 or >9).
Subjects will receive 18 weekly doses of MTX in addition to doses of adalimumab
arm group label: MTX 25 mg
other name: MTX
intervention type: Drug
intervention name: Adalimumab
description: Subjects will receive 18 weekly doses of adalimumab
arm group label: MTX 12.5
arm group label: MTX 25 mg
arm group label: Placebo
other name: Humira
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Brian Feagan, MD
role: Principal Investigator
affiliation: Robarts Research Institute - Western University
citation: Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516. Erratum In: N Engl J Med. 2006 May 18;354(20):2200.
PMID: 16339095
citation: Rutgeerts P, Van Assche G, Sandborn WJ, Wolf DC, Geboes K, Colombel JF, Reinisch W; EXTEND Investigators; Kumar A, Lazar A, Camez A, Lomax KG, Pollack PF, D'Haens G. Adalimumab induces and maintains mucosal healing in patients with Crohn's disease: data from the EXTEND trial. Gastroenterology. 2012 May;142(5):1102-1111.e2. doi: 10.1053/j.gastro.2012.01.035. Epub 2012 Feb 8.
PMID: 22326435
citation: Reinisch W, Sandborn WJ, Hommes DW, D'Haens G, Hanauer S, Schreiber S, Panaccione R, Fedorak RN, Tighe MB, Huang B, Kampman W, Lazar A, Thakkar R. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011 Jun;60(6):780-7. doi: 10.1136/gut.2010.221127. Epub 2011 Jan 5.
PMID: 21209123
citation: Baert F, Noman M, Vermeire S, Van Assche G, D' Haens G, Carbonez A, Rutgeerts P. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003 Feb 13;348(7):601-8. doi: 10.1056/NEJMoa020888.
PMID: 12584368
responsible party type: Sponsor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
mesh term: Adalimumab
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 