<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/NCT03287219</url>
  </required_header>
  <id_info>
    <org_study_id>CB-17-01/03</org_study_id>
    <nct_id>NCT03287219</nct_id>
  </id_info>
  <brief_title>Colon Staining Efficacy of Single Oral Doses of Methylene Blue MMX</brief_title>
  <acronym>CRO-11-108</acronym>
  <official_title>Colon Staining Efficacy of Single Oral Doses of Methylene Blue MMX® Modified Release Tablets Administered to Patients Undergoing Colonoscopy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cosmo Technologies Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cross S.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cosmo Pharmaceuticals NV</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To describe and evaluate the mucosal staining efficacy of Methylene Blue MMX® tablets after&#xD;
      total oral doses of 150 or 200 mg in patients undergoing a full colonoscopy for various&#xD;
      reasons.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives:&#xD;
&#xD;
      To describe and evaluate the mucosal staining efficacy of Methylene Blue MMX® tablets after&#xD;
      total oral doses of 150 or 200 mg in patients undergoing a full colonoscopy for various&#xD;
      reasons.&#xD;
&#xD;
      Primary end-point(s):&#xD;
&#xD;
      To evaluate the mucosal staining efficacy of Methylene Blue MMX® tablets after total oral&#xD;
      doses of 150 or 200 mg.&#xD;
&#xD;
      Secondary end-point(s):&#xD;
&#xD;
      Bowel cleansing quality evaluated according to the validated Boston Bowel Preparation Scale&#xD;
      (BBPS) after intake of 150 or 200 mg of Methylene Blue MMX® tablets during the intake of the&#xD;
      bowel cleansing preparation.&#xD;
&#xD;
      To collect data about safety and tolerability of Methylene Blue MMX® tablets after&#xD;
      administration of single oral doses of 150 or 200 mg.&#xD;
&#xD;
      Methodology:&#xD;
&#xD;
      Open label, staining efficacy exploratory study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2, 2011</start_date>
  <completion_date type="Actual">January 16, 2012</completion_date>
  <primary_completion_date type="Actual">January 16, 2012</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Open label, staining efficacy exploratory study.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>None. Open label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of Mucosal Staining Efficacy</measure>
    <time_frame>One day- mucosal staining efficacy is assessed during the colonoscopy procedure</time_frame>
    <description>Mucosal staining efficacy of Methylene Blue MMX tablets after total oral doses of 150 or 200 mg.&#xD;
Methylene blue staining efficacy was assessed by scoring the observed percentage of staining as reported below for each colon region (AC, TC, DC, RES) 0 - no staining&#xD;
- traces (poor traces in colon mucosa)&#xD;
- detectable (at least the 25% of colon mucosa is stained)&#xD;
- acceptable (at least the 50% of colon mucosa is stained)&#xD;
- good (at least the 75% of colon mucosa is stained)&#xD;
- over stained ( the 100% of the colon mucosa is over stained) After scoring (SC) separately each colonic segment, the total staining score (TSC) was also calculated and the number of regions with an SC&gt;2 (NSA) was determined.&#xD;
For each patient, the best effective TSC was set at 16, when SC=4 was detected in all 4 regions. SC=5 detected in any region and TSC&gt;16, both denoting an overstaining of the mucosa, were defined as suboptimal results in colon staining.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure)</measure>
    <time_frame>until study completion (until 2 days after dose)</time_frame>
    <description>safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (blood pressure)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability of Methylene Blue MMX as Determined by AEs</measure>
    <time_frame>Until study completion (until 2 days after dose)</time_frame>
    <description>Safety and tolerability of Methylene Blue MMX® tablets after administration of total oral doses of 150 or 200 mg.AEs were assessed throughout the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate</measure>
    <time_frame>until study completion (until 2 days after dose)</time_frame>
    <description>incidence of treatment emergent by measurement of vital signs (heart rate) to determine Safety and Tolerability of Methylene Blue MMX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood)</measure>
    <time_frame>until study completion (until 2 days after dose)</time_frame>
    <description>safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (Oxygen Saturation in peripheral blood)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and Tolerability of Methylene Blue MMX as Determined Body Weight.</measure>
    <time_frame>until study completion (until 2 days after dose)</time_frame>
    <description>safety and tolerability of Methylene Blue MMX in relation to incidence of treatment emergent by body weight.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bowel Cleansing Quality-Boston Bowel Preparation Score</measure>
    <time_frame>One day- bowel cleansing quality is assessed during the colonoscopy procedure</time_frame>
    <description>Bowel cleansing quality evaluated according to the validated Boston Bowel Preparation Scale (BBPS).&#xD;
Colon was divided into 4 target regions: ascending colon (AC), transverse colon (TC), descending colon (DC) and rectosigmoid (RES). Methylene blue staining efficacy was assessed scoring the observed staining percentage as reported below for each colon region:&#xD;
0 - no staining&#xD;
- traces (poor traces in colon mucosa)&#xD;
- detectable (at least the 25% of colon mucosa is stained)&#xD;
- acceptable (at least the 50% of colon mucosa is stained)&#xD;
- good (at least the 75% of colon mucosa is stained)&#xD;
- over stained ( the 100% of the colon mucosa is over stained)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">114</enrollment>
  <condition>Colon Staining in Preparation for Colonoscopy</condition>
  <arm_group>
    <arm_group_label>150 mg Methylene Blue-MMX tablets</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>take 6 x 25mg Methylene Blue-MMX tablets equivalent to 150 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200 mg Methylene Blue-MMX tablets</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>take 8 x 25mg Methylene Blue-MMX tablets equivalent to 200 mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylene Blue MMX 25 mg modified release tablets</intervention_name>
    <description>Methylene Blue MMX 25 mg modified release tablets administered with a full dose regimen of a 4-L PEG-based bowel cleansing preparation.</description>
    <arm_group_label>150 mg Methylene Blue-MMX tablets</arm_group_label>
    <arm_group_label>200 mg Methylene Blue-MMX tablets</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Sex: males and females;&#xD;
&#xD;
          2. Age:18 to 70 years;&#xD;
&#xD;
          3. Colonoscopy: out-patients with indication for colonoscopy including faecal occult&#xD;
             blood test positive colorectal cancer screening, polypectomy follow-up and&#xD;
             inflammatory bowel disease check;&#xD;
&#xD;
          4. Contraception: either sterile subjects or subjects practising at least one reliable&#xD;
             methods of contraception or in post-menopausal status for at least 1 year;&#xD;
&#xD;
          5. Informed Consent: signed written informed consent prior to inclusion in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnancy: pregnant or lactating women or at a risk of becoming pregnant;&#xD;
&#xD;
          2. Allergy: known or suspected hypersensitivity to the active principle and/or&#xD;
             formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in&#xD;
             general;&#xD;
&#xD;
          3. Diseases: known or suspected gastrointestinal obstruction or perforation, toxic&#xD;
             megacolon, major colonic resection, inflammatory bowel diseases in active phase,&#xD;
             severe diverticulosis with diverticulitis, heart failure (Class III or IV), serious&#xD;
             cardiovascular disease, severe liver failure, end-stage renal insufficiency, any other&#xD;
             relevant disease that might interfere with the aim of the study.&#xD;
&#xD;
          4. Comprehension: inability to comprehend the full nature and purpose of the study and&#xD;
             unwillingness to co-operate with the Investigator and to comply with the requirements&#xD;
             of the entire study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <results_first_submitted>December 1, 2017</results_first_submitted>
  <results_first_submitted_qc>January 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 28, 2021</results_first_posted>
  <last_update_submitted>January 8, 2021</last_update_submitted>
  <last_update_submitted_qc>January 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylene Blue</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>150 mg Methylene Blue-MMX Tablets</title>
          <description>take 6 x 25mg Methylene Blue-MMX tablets equivalent to 150 mg&#xD;
Methylene Blue MMX 25 mg modified release tablets: Methylene Blue MMX 25 mg modified release tablets administered with a full dose regimen of a 4-L PEG-based bowel cleansing preparation.</description>
        </group>
        <group group_id="P2">
          <title>200 mg Methylene Blue-MMX Tablets</title>
          <description>take 8 x 25mg Methylene Blue-MMX tablets equivalent to 200 mg&#xD;
Methylene Blue MMX 25 mg modified release tablets: Methylene Blue MMX 25 mg modified release tablets administered with a full dose regimen of a 4-L PEG-based bowel cleansing preparation.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="90"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="88"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Methylene Blue MMX 150mg</title>
          <description>Patients under going Colonoscpy taking Methylene Blue-MMX tablets equivalent to 150 mg</description>
        </group>
        <group group_id="B2">
          <title>Methylene Blue MMX 200mg</title>
          <description>Patients under going Colonoscpy taking Methylene Blue-MMX tablets equivalent to 200 mg</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="24"/>
            <count group_id="B2" value="88"/>
            <count group_id="B3" value="112"/>
          </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="50.4" spread="11.0"/>
                    <measurement group_id="B2" value="55.6" spread="11.2"/>
                    <measurement group_id="B3" value="54.5" spread="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>Centimetres</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="166.5" spread="8.4"/>
                    <measurement group_id="B2" value="168.5" spread="8.7"/>
                    <measurement group_id="B3" value="167.4" spread="8.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body 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="68" spread="13.3"/>
                    <measurement group_id="B2" value="70.6" spread="14.2"/>
                    <measurement group_id="B3" value="69" spread="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Evaluation of Mucosal Staining Efficacy</title>
        <description>Mucosal staining efficacy of Methylene Blue MMX tablets after total oral doses of 150 or 200 mg.&#xD;
Methylene blue staining efficacy was assessed by scoring the observed percentage of staining as reported below for each colon region (AC, TC, DC, RES) 0 - no staining&#xD;
- traces (poor traces in colon mucosa)&#xD;
- detectable (at least the 25% of colon mucosa is stained)&#xD;
- acceptable (at least the 50% of colon mucosa is stained)&#xD;
- good (at least the 75% of colon mucosa is stained)&#xD;
- over stained ( the 100% of the colon mucosa is over stained) After scoring (SC) separately each colonic segment, the total staining score (TSC) was also calculated and the number of regions with an SC&gt;2 (NSA) was determined.&#xD;
For each patient, the best effective TSC was set at 16, when SC=4 was detected in all 4 regions. SC=5 detected in any region and TSC&gt;16, both denoting an overstaining of the mucosa, were defined as suboptimal results in colon staining.</description>
        <time_frame>One day- mucosal staining efficacy is assessed during the colonoscopy procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>A (Dose:150mg)</title>
            <description>Number of tablets taken in relation to the intake of the bowel cleansing preparation:&#xD;
At the beginning - 2 After the 1st L - 2 After the 2nd L - 2 After the 3rd L - 0 At the end - 0</description>
          </group>
          <group group_id="O2">
            <title>B (Dose:150mg)</title>
            <description>Number of tablets taken in relation to the intake of the bowel cleansing preparation:&#xD;
At the beginning - 6 After the 1st L - 0 After the 2nd L- 0 After the 3rd L- 0 At the end- 0</description>
          </group>
          <group group_id="O3">
            <title>C (Dose:150mg)</title>
            <description>Number of tablets taken in relation to the intake of the bowel cleansing preparation:&#xD;
At the beginning - 0 After the 1st L - 0 After the 2nd L - 0 After the 3rd L - 0 At the end - 6</description>
          </group>
          <group group_id="O4">
            <title>D (Dose:200mg)</title>
            <description>Number of tablets taken in relation to the intake of the bowel cleansing preparation At the beginning -4 After the 1st L-2 After the 2nd L-2 After the 3rd L-0 At the end-0</description>
          </group>
          <group group_id="O5">
            <title>E (Dose:200mg)</title>
            <description>Number of tablets taken in relation to the intake of the bowel cleansing preparation At the beginning -0 After the 1st L-0 After the 2nd L-0 After the 3rd L-0 At the end-8</description>
          </group>
          <group group_id="O6">
            <title>F (Dose:200mg)</title>
            <description>Number of tablets taken in relation to the intake of the bowel cleansing preparation At the beginning -2 After the 1st L-2 After the 2nd L-2 After the 3rd L-0 At the end-2</description>
          </group>
          <group group_id="O7">
            <title>G (Dose 200mg)</title>
            <description>Number of tablets taken in relation to the intake of the bowel cleansing preparation At the beginning -4 After the 1st L-2 After the 2nd L-2 After the 3rd L-0 At the end-0</description>
          </group>
          <group group_id="O8">
            <title>H (Dose:200mg)</title>
            <description>Number of tablets taken in relation to the intake of the bowel cleansing preparation At the beginning -0 After the 1st L-0 After the 2nd L-0 After the 3rd L-4 At the end-4</description>
          </group>
          <group group_id="O9">
            <title>I (Dose:200mg)</title>
            <description>Number of tablets taken in relation to the intake of the bowel cleansing preparation At the beginning -0 After the 1st L-0 After the 2nd L-4 After the 3rd L-4 At the end-0</description>
          </group>
          <group group_id="O10">
            <title>J (Dose:200mg)</title>
            <description>Number of tablets taken in relation to the intake of the bowel cleansing preparation:&#xD;
At the beginning - 0 After the 1st L - 0 After the 2nd L - 2 After the 3rd L - 3 At the end - 3</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluation of Mucosal Staining Efficacy</title>
          <description>Mucosal staining efficacy of Methylene Blue MMX tablets after total oral doses of 150 or 200 mg.&#xD;
Methylene blue staining efficacy was assessed by scoring the observed percentage of staining as reported below for each colon region (AC, TC, DC, RES) 0 - no staining&#xD;
- traces (poor traces in colon mucosa)&#xD;
- detectable (at least the 25% of colon mucosa is stained)&#xD;
- acceptable (at least the 50% of colon mucosa is stained)&#xD;
- good (at least the 75% of colon mucosa is stained)&#xD;
- over stained ( the 100% of the colon mucosa is over stained) After scoring (SC) separately each colonic segment, the total staining score (TSC) was also calculated and the number of regions with an SC&gt;2 (NSA) was determined.&#xD;
For each patient, the best effective TSC was set at 16, when SC=4 was detected in all 4 regions. SC=5 detected in any region and TSC&gt;16, both denoting an overstaining of the mucosa, were defined as suboptimal results in colon staining.</description>
          <units>scores 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="8"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="20"/>
                <count group_id="O5" value="9"/>
                <count group_id="O6" value="8"/>
                <count group_id="O7" value="2"/>
                <count group_id="O8" value="20"/>
                <count group_id="O9" value="16"/>
                <count group_id="O10" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" spread="4.0"/>
                    <measurement group_id="O2" value="2.3" spread="2.4"/>
                    <measurement group_id="O3" value="8.1" spread="3.6"/>
                    <measurement group_id="O4" value="7.0" spread="5.0"/>
                    <measurement group_id="O5" value="9.8" spread="4.1"/>
                    <measurement group_id="O6" value="10.5" spread="4.1"/>
                    <measurement group_id="O7" value="10.5" spread="7.8"/>
                    <measurement group_id="O8" value="10.0" spread="3.2"/>
                    <measurement group_id="O9" value="11.4" spread="3.8"/>
                    <measurement group_id="O10" value="11.6" spread="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure)</title>
        <description>safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (blood pressure)</description>
        <time_frame>until study completion (until 2 days after dose)</time_frame>
        <population>Safety population: the safety population was defined as all enrolled subjects who received at least one dose of the study drug. This population was used for safety evaluation</population>
        <group_list>
          <group group_id="O1">
            <title>Pre Colonoscopy - 150mg Dose</title>
            <description>Vital Signs - safety Population -- 150mg dose</description>
          </group>
          <group group_id="O2">
            <title>Pre Colonoscopy- 200mg Dose</title>
            <description>Vital Signs - safety Population- 200mg dose</description>
          </group>
          <group group_id="O3">
            <title>During Colonoscopy- 150mg Dose</title>
            <description>Vital Signs - safety Population- 150mg dose</description>
          </group>
          <group group_id="O4">
            <title>During Colonoscopy- 200mg Dose</title>
            <description>Vital Signs - safety Population- 200mg dose</description>
          </group>
          <group group_id="O5">
            <title>Post Colonoscopy- 150mg Dose</title>
            <description>Vital Signs - safety Population- 150mg dose</description>
          </group>
          <group group_id="O6">
            <title>Post Colonoscopy- 200mg Dose</title>
            <description>Vital Signs - safety Population- 200mg dose</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure)</title>
          <description>safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (blood pressure)</description>
          <population>Safety population: the safety population was defined as all enrolled subjects who received at least one dose of the study drug. This population was used for safety evaluation</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="88"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="86"/>
                <count group_id="O5" value="24"/>
                <count group_id="O6" value="87"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Systolic Blood Pressure (mmHg)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="122.6" spread="14.6"/>
                    <measurement group_id="O2" value="124.3" spread="17.7"/>
                    <measurement group_id="O3" value="122.6" spread="14.6"/>
                    <measurement group_id="O4" value="124.3" spread="17.7"/>
                    <measurement group_id="O5" value="122.7" spread="14.5"/>
                    <measurement group_id="O6" value="124.2" spread="17.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic Blood Pressure(mmHg)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.7" spread="8.1"/>
                    <measurement group_id="O2" value="74.0" spread="11.9"/>
                    <measurement group_id="O3" value="74.9" spread="8.2"/>
                    <measurement group_id="O4" value="74.0" spread="11.9"/>
                    <measurement group_id="O5" value="75" spread="8.2"/>
                    <measurement group_id="O6" value="74.0" spread="11.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety and Tolerability of Methylene Blue MMX as Determined by AEs</title>
        <description>Safety and tolerability of Methylene Blue MMX® tablets after administration of total oral doses of 150 or 200 mg.AEs were assessed throughout the study.</description>
        <time_frame>Until study completion (until 2 days after dose)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pre Colonoscopy - 150mg Dose</title>
            <description>Vital Signs - safety Population -- 150mg dose</description>
          </group>
          <group group_id="O2">
            <title>Pre Colonoscopy- 200mg Dose</title>
            <description>Vital Signs - safety Population- 200mg dose</description>
          </group>
          <group group_id="O3">
            <title>During Colonoscopy- 150mg Dose</title>
            <description>Vital Signs - safety Population- 150mg dose</description>
          </group>
          <group group_id="O4">
            <title>During Colonoscopy- 200mg Dose</title>
            <description>Vital Signs - safety Population- 200mg dose</description>
          </group>
          <group group_id="O5">
            <title>Post Colonoscopy- 150mg Dose</title>
            <description>Vital Signs - safety Population- 150mg dose</description>
          </group>
          <group group_id="O6">
            <title>Post Colonoscopy- 200mg Dose</title>
            <description>Vital Signs - safety Population- 200mg dose</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability of Methylene Blue MMX as Determined by AEs</title>
          <description>Safety and tolerability of Methylene Blue MMX® tablets after administration of total oral doses of 150 or 200 mg.AEs were assessed throughout the study.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="88"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="86"/>
                <count group_id="O5" value="24"/>
                <count group_id="O6" value="87"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate</title>
        <description>incidence of treatment emergent by measurement of vital signs (heart rate) to determine Safety and Tolerability of Methylene Blue MMX</description>
        <time_frame>until study completion (until 2 days after dose)</time_frame>
        <population>Safety population: the safety population was defined as all enrolled subjects who received at least one dose of the study drug. This population was used for safety evaluation</population>
        <group_list>
          <group group_id="O1">
            <title>Pre Colonoscopy - 150mg Dose</title>
            <description>Vital Signs - safety Population - 150mg dose</description>
          </group>
          <group group_id="O2">
            <title>Pre Colonoscopy- 200mg Dose</title>
            <description>Vital Signs - safety Population - 200mg dose</description>
          </group>
          <group group_id="O3">
            <title>During Colonoscopy - 150mg Dose</title>
            <description>Vital Signs - safety Population - 150mg dose</description>
          </group>
          <group group_id="O4">
            <title>During Colonoscopy- 200mg Dose</title>
            <description>Vital Signs - safety Population - 200mg dose</description>
          </group>
          <group group_id="O5">
            <title>Post Colonoscopy- 150mg Dose</title>
            <description>Vital Signs - safety Population - 150mg dose</description>
          </group>
          <group group_id="O6">
            <title>Post Colonoscopy- 200mg Dose</title>
            <description>Vital Signs - safety Population - 200mg dose</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate</title>
          <description>incidence of treatment emergent by measurement of vital signs (heart rate) to determine Safety and Tolerability of Methylene Blue MMX</description>
          <population>Safety population: the safety population was defined as all enrolled subjects who received at least one dose of the study drug. This population was used for safety evaluation</population>
          <units>beats per minute (BPM)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="87"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="85"/>
                <count group_id="O5" value="24"/>
                <count group_id="O6" value="87"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.9" spread="10.6"/>
                    <measurement group_id="O2" value="75.2" spread="15.1"/>
                    <measurement group_id="O3" value="74.3" spread="10.9"/>
                    <measurement group_id="O4" value="75.3" spread="15.1"/>
                    <measurement group_id="O5" value="74.2" spread="10.9"/>
                    <measurement group_id="O6" value="7.1" spread="15.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood)</title>
        <description>safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (Oxygen Saturation in peripheral blood)</description>
        <time_frame>until study completion (until 2 days after dose)</time_frame>
        <population>Safety population: the safety population was defined as all enrolled subjects who received at least one dose of the study drug. This population was used for safety evaluation</population>
        <group_list>
          <group group_id="O1">
            <title>Pre Colonoscopy - 150mg Dose</title>
            <description>Vital Signs - safety Population</description>
          </group>
          <group group_id="O2">
            <title>Pre Colonoscopy- 200mg Dose</title>
          </group>
          <group group_id="O3">
            <title>During Colonoscopy- 150mg Dose</title>
            <description>Vital Signs - safety Population</description>
          </group>
          <group group_id="O4">
            <title>During Colonoscopy- 200mg Dose</title>
          </group>
          <group group_id="O5">
            <title>Post Colonoscopy- 150mg Dose</title>
            <description>Vital Signs - safety Population</description>
          </group>
          <group group_id="O6">
            <title>Post Colonoscopy- 200mg Dose</title>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood)</title>
          <description>safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (Oxygen Saturation in peripheral blood)</description>
          <population>Safety population: the safety population was defined as all enrolled subjects who received at least one dose of the study drug. This population was used for safety evaluation</population>
          <units>percentage of saturation</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="88"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="86"/>
                <count group_id="O5" value="24"/>
                <count group_id="O6" value="87"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.4" spread="1.8"/>
                    <measurement group_id="O2" value="98.7" spread="6.6"/>
                    <measurement group_id="O3" value="98.4" spread="1.8"/>
                    <measurement group_id="O4" value="98.8" spread="6.5"/>
                    <measurement group_id="O5" value="98.4" spread="1.8"/>
                    <measurement group_id="O6" value="98.8" spread="6.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety and Tolerability of Methylene Blue MMX as Determined Body Weight.</title>
        <description>safety and tolerability of Methylene Blue MMX in relation to incidence of treatment emergent by body weight.</description>
        <time_frame>until study completion (until 2 days after dose)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Visit 1-Screening 150mL</title>
            <description>Safety Population 150mL Dose</description>
          </group>
          <group group_id="O2">
            <title>Visit 1-Screening 200mL</title>
            <description>Safety Population 200mL Dose</description>
          </group>
          <group group_id="O3">
            <title>Visit 2-Final 150mL</title>
            <description>Safety Population 150mL Dose</description>
          </group>
          <group group_id="O4">
            <title>Visit 2-Final 200mL</title>
            <description>Safety Population 200mL Dose</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability of Methylene Blue MMX as Determined Body Weight.</title>
          <description>safety and tolerability of Methylene Blue MMX in relation to incidence of treatment emergent by body weight.</description>
          <units>Kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="89"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="89"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.2" spread="13.0"/>
                    <measurement group_id="O2" value="71.3" spread="15.9"/>
                    <measurement group_id="O3" value="67.4" spread="13.0"/>
                    <measurement group_id="O4" value="71.2" spread="15.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bowel Cleansing Quality-Boston Bowel Preparation Score</title>
        <description>Bowel cleansing quality evaluated according to the validated Boston Bowel Preparation Scale (BBPS).&#xD;
Colon was divided into 4 target regions: ascending colon (AC), transverse colon (TC), descending colon (DC) and rectosigmoid (RES). Methylene blue staining efficacy was assessed scoring the observed staining percentage as reported below for each colon region:&#xD;
0 - no staining&#xD;
- traces (poor traces in colon mucosa)&#xD;
- detectable (at least the 25% of colon mucosa is stained)&#xD;
- acceptable (at least the 50% of colon mucosa is stained)&#xD;
- good (at least the 75% of colon mucosa is stained)&#xD;
- over stained ( the 100% of the colon mucosa is over stained)</description>
        <time_frame>One day- bowel cleansing quality is assessed during the colonoscopy procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>150 mg Methylene Blue-MMX Tablets</title>
            <description>take 6 x 25mg Methylene Blue-MMX tablets equivalent to 150 mg&#xD;
Methylene Blue MMX 25 mg modified release tablets: Methylene Blue MMX 25 mg modified release tablets administered with a full dose regimen of a 4-L PEG-based bowel cleansing preparation.</description>
          </group>
          <group group_id="O2">
            <title>200 mg Methylene Blue-MMX Tablets</title>
            <description>take 8 x 25mg Methylene Blue-MMX tablets equivalent to 200 mg&#xD;
Methylene Blue MMX 25 mg modified release tablets: Methylene Blue MMX 25 mg modified release tablets administered with a full dose regimen of a 4-L PEG-based bowel cleansing preparation.</description>
          </group>
          <group group_id="O3">
            <title>Overall</title>
            <description>Overall Colon cleansing score</description>
          </group>
        </group_list>
        <measure>
          <title>Bowel Cleansing Quality-Boston Bowel Preparation Score</title>
          <description>Bowel cleansing quality evaluated according to the validated Boston Bowel Preparation Scale (BBPS).&#xD;
Colon was divided into 4 target regions: ascending colon (AC), transverse colon (TC), descending colon (DC) and rectosigmoid (RES). Methylene blue staining efficacy was assessed scoring the observed staining percentage as reported below for each colon region:&#xD;
0 - no staining&#xD;
- traces (poor traces in colon mucosa)&#xD;
- detectable (at least the 25% of colon mucosa is stained)&#xD;
- acceptable (at least the 50% of colon mucosa is stained)&#xD;
- good (at least the 75% of colon mucosa is stained)&#xD;
- over stained ( the 100% of the colon mucosa is over stained)</description>
          <units>Colon cleansing score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="88"/>
                <count group_id="O3" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" spread="1.7"/>
                    <measurement group_id="O2" value="5.4" spread="1.1"/>
                    <measurement group_id="O3" value="5.4" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>AEs Methylene Blue-MMX Tablets Equivalent to 150 mg</title>
          <description>Patients under going Colonoscpy taking Methylene Blue MMX Dose 150mL</description>
        </group>
        <group group_id="E2">
          <title>AEs Methylene Blue-MMX Tablets Equivalent to 200 mg</title>
          <description>Patients under going Colonoscpy taking Methylene Blue MMX dose 200 mg</description>
        </group>
      </group_list>
      <serious_events>
        <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="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>R&amp;D Manager</name_or_title>
      <organization>Cosmo Technologies Ltd</organization>
      <email>rjones@cosmopharma.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/NCT03287219
org study id: CB-17-01/03
nct id: NCT03287219
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To describe and evaluate the mucosal staining efficacy of Methylene Blue MMX® tablets after
      total oral doses of 150 or 200 mg in patients undergoing a full colonoscopy for various
      reasons.
Objectives:

      To describe and evaluate the mucosal staining efficacy of Methylene Blue MMX® tablets after
      total oral doses of 150 or 200 mg in patients undergoing a full colonoscopy for various
      reasons.

      Primary end-point(s):

      To evaluate the mucosal staining efficacy of Methylene Blue MMX® tablets after total oral
      doses of 150 or 200 mg.

      Secondary end-point(s):

      Bowel cleansing quality evaluated according to the validated Boston Bowel Preparation Scale
      (BBPS) after intake of 150 or 200 mg of Methylene Blue MMX® tablets during the intake of the
      bowel cleansing preparation.

      To collect data about safety and tolerability of Methylene Blue MMX® tablets after
      administration of single oral doses of 150 or 200 mg.

      Methodology:

      Open label, staining efficacy exploratory study.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Open label, staining efficacy exploratory study.
primary purpose: Diagnostic
masking: None (Open Label)
masking description: None. Open label
measure: Evaluation of Mucosal Staining Efficacy
time frame: One day- mucosal staining efficacy is assessed during the colonoscopy procedure
description: Mucosal staining efficacy of Methylene Blue MMX tablets after total oral doses of 150 or 200 mg.
Methylene blue staining efficacy was assessed by scoring the observed percentage of staining as reported below for each colon region (AC, TC, DC, RES) 0 - no staining
- traces (poor traces in colon mucosa)
- detectable (at least the 25% of colon mucosa is stained)
- acceptable (at least the 50% of colon mucosa is stained)
- good (at least the 75% of colon mucosa is stained)
- over stained ( the 100% of the colon mucosa is over stained) After scoring (SC) separately each colonic segment, the total staining score (TSC) was also calculated and the number of regions with an SC>2 (NSA) was determined.
For each patient, the best effective TSC was set at 16, when SC=4 was detected in all 4 regions. SC=5 detected in any region and TSC>16, both denoting an overstaining of the mucosa, were defined as suboptimal results in colon staining.
measure: Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Blood Pressure)
time frame: until study completion (until 2 days after dose)
description: safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (blood pressure)
measure: Safety and Tolerability of Methylene Blue MMX as Determined by AEs
time frame: Until study completion (until 2 days after dose)
description: Safety and tolerability of Methylene Blue MMX® tablets after administration of total oral doses of 150 or 200 mg.AEs were assessed throughout the study.
measure: Safety and Tolerability of Methylene Blue MMX as Determined by Heart Rate
time frame: until study completion (until 2 days after dose)
description: incidence of treatment emergent by measurement of vital signs (heart rate) to determine Safety and Tolerability of Methylene Blue MMX
measure: Safety and Tolerability of Methylene Blue MMX as Determined by Vital Signs (Oxygen Saturation in Peripheral Blood)
time frame: until study completion (until 2 days after dose)
description: safety and tolerability of Methylene Blue MMX reviewed by incidence of treatment emergent by measurement of vital signs (Oxygen Saturation in peripheral blood)
measure: Safety and Tolerability of Methylene Blue MMX as Determined Body Weight.
time frame: until study completion (until 2 days after dose)
description: safety and tolerability of Methylene Blue MMX in relation to incidence of treatment emergent by body weight.
measure: Bowel Cleansing Quality-Boston Bowel Preparation Score
time frame: One day- bowel cleansing quality is assessed during the colonoscopy procedure
description: Bowel cleansing quality evaluated according to the validated Boston Bowel Preparation Scale (BBPS).
Colon was divided into 4 target regions: ascending colon (AC), transverse colon (TC), descending colon (DC) and rectosigmoid (RES). Methylene blue staining efficacy was assessed scoring the observed staining percentage as reported below for each colon region:
0 - no staining
- traces (poor traces in colon mucosa)
- detectable (at least the 25% of colon mucosa is stained)
- acceptable (at least the 50% of colon mucosa is stained)
- good (at least the 75% of colon mucosa is stained)
- over stained ( the 100% of the colon mucosa is over stained)
arm group label: 150 mg Methylene Blue-MMX tablets
arm group type: Active Comparator
description: take 6 x 25mg Methylene Blue-MMX tablets equivalent to 150 mg
arm group label: 200 mg Methylene Blue-MMX tablets
arm group type: Active Comparator
description: take 8 x 25mg Methylene Blue-MMX tablets equivalent to 200 mg
intervention type: Drug
intervention name: Methylene Blue MMX 25 mg modified release tablets
description: Methylene Blue MMX 25 mg modified release tablets administered with a full dose regimen of a 4-L PEG-based bowel cleansing preparation.
arm group label: 150 mg Methylene Blue-MMX tablets
arm group label: 200 mg Methylene Blue-MMX tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Sponsor
mesh term: Methylene Blue
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 