<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/NCT02220920</url>
  </required_header>
  <id_info>
    <org_study_id>TA-7284-11</org_study_id>
    <nct_id>NCT02220920</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of Canagliflozin (TA-7284) in Combination With Insulin in Patients With Type 2 Diabetes Mellitus</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin (TA-7284) as add-on to Insulin in Subjects With Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mitsubishi Tanabe Pharma Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mitsubishi Tanabe Pharma Corporation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy and safety of Canagliflozin (TA-7284)&#xD;
      in combination with Insulin in patients with type 2 Diabetes for 16 weeks administration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, 2-arm, parallel group, double blind study to evaluate the efficacy and&#xD;
      safety of Canagliflozin (TA-7284) in Japanese patients with type 2 diabetes mellitus, who are&#xD;
      receiving treatment with insulin therapy on diet and exercise and have inadequate glycemic&#xD;
      control. The patients will receive either TA-7284 100mg or Placebo orally for 16 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HbA1c From Baseline</measure>
    <time_frame>baseline and Week 16</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Fasting Plasma Glucose</measure>
    <time_frame>baseline and Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Body Weight</measure>
    <time_frame>baseline and Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Blood Pressure</measure>
    <time_frame>baseline and Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With &quot;Adverse Events&quot; and &quot;Hypoglycemia and Blood Glucose Decreased&quot;</measure>
    <time_frame>Week 16</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">146</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Canagliflozin (TA-7284) ＋insulin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo＋insulin</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Canagliflozin (TA-7284)</intervention_name>
    <description>The patients will receive Canagliflozin orally for 16 weeks</description>
    <arm_group_label>Canagliflozin (TA-7284) ＋insulin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The patients will receive Placebo orally for 16 weeks</description>
    <arm_group_label>Placebo＋insulin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin</intervention_name>
    <arm_group_label>Canagliflozin (TA-7284) ＋insulin</arm_group_label>
    <arm_group_label>Placebo＋insulin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who has been receiving a stable dose and regimen of insulin over 12 weeks&#xD;
             before administration of investigational dug&#xD;
&#xD;
          -  Patients who are under dietary management and taking therapeutic exercise for diabetes&#xD;
             over 12 weeks before administration of investigational drug&#xD;
&#xD;
          -  Patients with HbA1c of ≥7.5% and &lt;10.5%&#xD;
&#xD;
          -  Patients who were not administered diabetes therapeutic drugs prohibited for&#xD;
             concomitant use within 12 weeks before administration of investigational drug&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with type 1 diabetes mellitus, diabetes mellitus resulting from pancreatic&#xD;
             disorder, or secondary diabetes mellitus (Cushing's syndrome, acromegaly, etc.)&#xD;
&#xD;
          -  Patients with severe diabetic complications (proliferative diabetic retinopathy, stage&#xD;
             4 nephropathy, or serious diabetic neuropathy)&#xD;
&#xD;
          -  Patients with hereditary glucose-galactose malabsorption or primary renal glucosuria&#xD;
&#xD;
          -  Patients with systolic blood pressure of ≥160 mmHg or diastolic blood pressure of ≥100&#xD;
             mmHg&#xD;
&#xD;
          -  Patients with serious renal or hepatic disease&#xD;
&#xD;
          -  Patients with eGFR of &lt;45 mL/min/1.73 m2&#xD;
&#xD;
          -  Patients who are the excessive alcohol addicts&#xD;
&#xD;
          -  Patients who are pregnant, lactating and probably pregnant patients and patients who&#xD;
             can not agree to contraception&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kazuoki Kondo, MD</last_name>
    <role>Study Director</role>
    <affiliation>Mitsubishi Tanabe Pharma Corporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Reserch site</name>
      <address>
        <city>Chubu</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reserch site</name>
      <address>
        <city>Chugoku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reserch site</name>
      <address>
        <city>Hokkaido</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reserch site</name>
      <address>
        <city>Kanto</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reserch site</name>
      <address>
        <city>Kinki</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reserch site</name>
      <address>
        <city>Kyushu</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reserch site</name>
      <address>
        <city>Tohoku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <results_reference>
    <citation>Inagaki N, Harashima S, Maruyama N, Kawaguchi Y, Goda M, Iijima H. Efficacy and safety of canagliflozin in combination with insulin: a double-blind, randomized, placebo-controlled study in Japanese patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2016 Jun 18;15:89. doi: 10.1186/s12933-016-0407-4.</citation>
    <PMID>27316668</PMID>
  </results_reference>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <results_first_submitted>August 3, 2016</results_first_submitted>
  <results_first_submitted_qc>October 24, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 15, 2016</results_first_posted>
  <last_update_submitted>October 24, 2016</last_update_submitted>
  <last_update_submitted_qc>October 24, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>insulin resistance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Canagliflozin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Canagliflozin (TA-7284) ＋Insulin</title>
          <description>Canagliflozin, once daily for 16 weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo＋Insulin</title>
          <description>Placebo, once daily for 16 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="76"/>
                <participants group_id="P2" count="70"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="73"/>
                <participants group_id="P2" count="67"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Conflict with the stopping criteria</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <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>Canagliflozin (TA-7284) ＋Insulin</title>
          <description>Canagliflozin, once daily for 16 weeks</description>
        </group>
        <group group_id="B2">
          <title>Placebo＋Insulin</title>
          <description>Placebo, once daily for 16 weeks</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="76"/>
            <count group_id="B2" value="70"/>
            <count group_id="B3" value="146"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="95"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="32"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in HbA1c From Baseline</title>
        <time_frame>baseline and Week 16</time_frame>
        <population>Full analysis set, last observation carried forward</population>
        <group_list>
          <group group_id="O1">
            <title>Canagliflozin (TA-7284) ＋Insulin</title>
            <description>Canagliflozin, once daily for 16 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo＋Insulin</title>
            <description>Placebo, once daily for 16 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change in HbA1c From Baseline</title>
          <population>Full analysis set, last observation carried forward</population>
          <units>Percent</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="76"/>
                <count group_id="O2" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.97" spread="0.08"/>
                    <measurement group_id="O2" value="0.13" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>Least-Squares Mean Difference</param_type>
            <param_value>-1.10</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.11</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.33</ci_lower_limit>
            <ci_upper_limit>-0.87</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Fasting Plasma Glucose</title>
        <time_frame>baseline and Week 16</time_frame>
        <population>Full analysis set, last observation carried forward. There was a lack of measurement of fasting plasma glucose at the end of treatment visit(Week 4) in one participant who was randomized to &quot;Canagliflozin(TA-7284) + Insulin&quot; group.</population>
        <group_list>
          <group group_id="O1">
            <title>Canagliflozin (TA-7284) ＋Insulin</title>
            <description>Canagliflozin, once daily for 16 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo＋Insulin</title>
            <description>Placebo, once daily for 16 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Fasting Plasma Glucose</title>
          <population>Full analysis set, last observation carried forward. There was a lack of measurement of fasting plasma glucose at the end of treatment visit(Week 4) in one participant who was randomized to &quot;Canagliflozin(TA-7284) + Insulin&quot; group.</population>
          <units>mg/dL</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-34.1" spread="4.8"/>
                    <measurement group_id="O2" value="-1.4" spread="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>Least-Squares Mean Difference</param_type>
            <param_value>-32.6</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>6.9</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-46.3</ci_lower_limit>
            <ci_upper_limit>-18.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Body Weight</title>
        <time_frame>baseline and Week 16</time_frame>
        <population>Full analysis set, last observation carried forward. There was a lack of measurement of body weight at the end of treatment visit(Week 4) in one participant who was randomized to &quot;Canagliflozin(TA-7284) + Insulin&quot; group.</population>
        <group_list>
          <group group_id="O1">
            <title>Canagliflozin (TA-7284) ＋Insulin</title>
            <description>Canagliflozin, once daily for 16 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo＋Insulin</title>
            <description>Placebo, once daily for 16 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Body Weight</title>
          <population>Full analysis set, last observation carried forward. There was a lack of measurement of body weight at the end of treatment visit(Week 4) in one participant who was randomized to &quot;Canagliflozin(TA-7284) + Insulin&quot; group.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.13" spread="0.25"/>
                    <measurement group_id="O2" value="0.24" spread="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>Least-Squares Mean Difference</param_type>
            <param_value>-2.37</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.36</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.09</ci_lower_limit>
            <ci_upper_limit>-1.65</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Blood Pressure</title>
        <time_frame>baseline and Week 16</time_frame>
        <population>Full analysis set, last observation carried forward</population>
        <group_list>
          <group group_id="O1">
            <title>Canagliflozin (TA-7284) ＋Insulin</title>
            <description>Canagliflozin, once daily for 16 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo＋Insulin</title>
            <description>Placebo, once daily for 16 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Blood Pressure</title>
          <population>Full analysis set, last observation carried forward</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="76"/>
                <count group_id="O2" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Systolic blood pressure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.58" spread="1.14"/>
                    <measurement group_id="O2" value="-0.40" spread="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diastolic blood pressure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.55" spread="0.71"/>
                    <measurement group_id="O2" value="-0.31" spread="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.058</p_value>
            <method>ANCOVA</method>
            <param_type>Least-Squares Mean Difference</param_type>
            <param_value>-3.19</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.67</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.49</ci_lower_limit>
            <ci_upper_limit>0.11</ci_upper_limit>
            <estimate_desc>Estimated P-Value, Least-Squares Mean Difference, Standard Error of the mean, 95% CI are presented for the change from Baseline in systolic blood pressure for week 16.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.232</p_value>
            <method>ANCOVA</method>
            <param_type>Least-Squares Mean Difference</param_type>
            <param_value>-1.24</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.03</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.27</ci_lower_limit>
            <ci_upper_limit>0.80</ci_upper_limit>
            <estimate_desc>Estimated P-Value, Least-Squares Mean Difference, Standard Error of the mean, 95% CI are presented for the change from Baseline in diastolic blood pressure for week 16.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With &quot;Adverse Events&quot; and &quot;Hypoglycemia and Blood Glucose Decreased&quot;</title>
        <time_frame>Week 16</time_frame>
        <population>Safety analysis set. &quot;Safety Population&quot; reflects the &quot;as treated&quot; population, and one &quot;Canagliflozin (TA-7284) + Insulin&quot; participant actually received &quot;Placebo + Insulin&quot;.</population>
        <group_list>
          <group group_id="O1">
            <title>Canagliflozin (TA-7284) ＋Insulin</title>
            <description>Canagliflozin, once daily for 16 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo＋Insulin</title>
            <description>Placebo, once daily for 16 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With &quot;Adverse Events&quot; and &quot;Hypoglycemia and Blood Glucose Decreased&quot;</title>
          <population>Safety analysis set. &quot;Safety Population&quot; reflects the &quot;as treated&quot; population, and one &quot;Canagliflozin (TA-7284) + Insulin&quot; participant actually received &quot;Placebo + Insulin&quot;.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="71"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.0"/>
                    <measurement group_id="O2" value="64.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycemia and Blood glucose decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.0"/>
                    <measurement group_id="O2" value="29.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>&quot;Safety Population&quot; reflects the &quot;as treated&quot; population, and one &quot;Canagliflozin(TA-7284) + Insulin&quot; participant actually received &quot;Placebo + Insulin&quot;.</desc>
      <group_list>
        <group group_id="E1">
          <title>Canagliflozin (TA-7284) ＋Insulin</title>
          <description>Canagliflozin, once daily for 16 weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo＋Insulin</title>
          <description>Placebo, once daily for 16 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 18.0</default_vocab>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="75"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="75"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="75"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Vitreous haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="75"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Alcoholic liver disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="75"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 18.0</default_vocab>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="75"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="75"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood glucose decreased</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="75"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="75"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="75"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="71"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trials, Information Desk</name_or_title>
      <organization>Mitsubishi Tanabe Pharma Corporation</organization>
      <email>cti-inq-ml@ml.mt-pharma.co.jp</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/NCT02220920
org study id: TA-7284-11
nct id: NCT02220920
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the efficacy and safety of Canagliflozin (TA-7284)
      in combination with Insulin in patients with type 2 Diabetes for 16 weeks administration.
This is a randomized, 2-arm, parallel group, double blind study to evaluate the efficacy and
      safety of Canagliflozin (TA-7284) in Japanese patients with type 2 diabetes mellitus, who are
      receiving treatment with insulin therapy on diet and exercise and have inadequate glycemic
      control. The patients will receive either TA-7284 100mg or Placebo orally for 16 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Change in HbA1c From Baseline
time frame: baseline and Week 16
measure: Change in Fasting Plasma Glucose
time frame: baseline and Week 16
measure: Percent Change in Body Weight
time frame: baseline and Week 16
measure: Change in Blood Pressure
time frame: baseline and Week 16
measure: Percentage of Participants With "Adverse Events" and "Hypoglycemia and Blood Glucose Decreased"
time frame: Week 16
arm group label: Canagliflozin (TA-7284) ＋insulin
arm group type: Experimental
arm group label: Placebo＋insulin
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Canagliflozin (TA-7284)
description: The patients will receive Canagliflozin orally for 16 weeks
arm group label: Canagliflozin (TA-7284) ＋insulin
intervention type: Drug
intervention name: Placebo
description: The patients will receive Placebo orally for 16 weeks
arm group label: Placebo＋insulin
intervention type: Drug
intervention name: Insulin
arm group label: Canagliflozin (TA-7284) ＋insulin
arm group label: Placebo＋insulin
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Kazuoki Kondo, MD
role: Study Director
affiliation: Mitsubishi Tanabe Pharma Corporation
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Japan
citation: Inagaki N, Harashima S, Maruyama N, Kawaguchi Y, Goda M, Iijima H. Efficacy and safety of canagliflozin in combination with insulin: a double-blind, randomized, placebo-controlled study in Japanese patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2016 Jun 18;15:89. doi: 10.1186/s12933-016-0407-4.
PMID: 27316668
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Canagliflozin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 