<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/NCT01684943</url>
  </required_header>
  <id_info>
    <org_study_id>2010P001005</org_study_id>
    <nct_id>NCT01684943</nct_id>
  </id_info>
  <brief_title>Selecting Insulin Analogs for Closed-Loop Control Using Multiplex Pharmacokinetic Profiling</brief_title>
  <official_title>Selecting Insulin Analogs for Closed-Loop Control Using Multiplex Pharmacokinetic Profiling</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are doing this research study to compare the pharmacokinetics (PK) (rate of&#xD;
      absorption) of insulin lispro (Humalog), insulin aspart (Novolog), and insulin glulisine&#xD;
      (Apidra) within individual subjects.&#xD;
&#xD;
      Additionally, the investigators will perform a preliminary feasibility evaluation of a&#xD;
      minimally invasive continuous insulin monitoring (CIM) device and its use to derive PK&#xD;
      parameters in human subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2010</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>All subjects participated in the single arm of the study. Some subjects participated in the continuous insulin monitoring sub-study in addition to the main protocol, or separate from the main protocol.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>For Multiplex PK Profiling: Aggregate Mean Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax for Individuals</measure>
    <time_frame>10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose</time_frame>
    <description>The average difference in tmax between lispro and aspart in all participants</description>
  </primary_outcome>
  <primary_outcome>
    <measure>For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin</measure>
    <time_frame>10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual</measure>
    <time_frame>Baseline</time_frame>
    <description>Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average A1c for each of the three categories is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiplex PK: Count of Subjects With Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax That is &gt; 25%</measure>
    <time_frame>10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog With Tmax &lt; 60 Minutes vs. Use of an Insulin Analog With Tmax &gt; 60 Minutes for Each Individual</measure>
    <time_frame>Baseline</time_frame>
    <description>Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with tmax less than or equal to 60 minutes or using insulin with tmax &gt; 60 minutes. The average A1c per group is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiplex PK: Average Number of Hypoglycemia Events Over the Last Month at Baseline Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual</measure>
    <time_frame>1 month prior to study entry</time_frame>
    <description>Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average number of hypoglycemic events per month per group is reported.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Multiplex pharmacokinetic profiling</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiplex pharmacokinetic profiling of regular human insulin, insulin aspart, insulin lispro, insulin glulisine, and regular human insulin. All subjects participated in the single study arm and received injections of each type of insulin. Blood samples were drawn at intervals for pharmacokinetic profiling.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous insulin monitoring</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Continuous insulin monitoring (CIM) of insulin lispro. Some subjects participated in the CIM sub-study, which is distinct from the Multiplex Pharmacokinetic Profiling study. This intervention involved administering insulin lispro and monitoring pharmacokinetic profile of the drug using blood samples and an investigational continuous insulin monitoring system.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Multiplex pharmacokinetic profiling</intervention_name>
    <arm_group_label>Multiplex pharmacokinetic profiling</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Continuous insulin monitoring</intervention_name>
    <arm_group_label>Continuous insulin monitoring</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older with clinical type 1 diabetes for at least five years&#xD;
&#xD;
          -  Diabetes managed using an insulin infusion pump and rapid- or very-rapid-acting&#xD;
             insulins including insulin aspart (NovoLog), insulin lispro (Humalog), and insulin&#xD;
             glulisine (Apidra).&#xD;
&#xD;
          -  Ability to consume a sufficient amount of carbohydrates over 2-3 hours to cover 9&#xD;
             units of rapid acting insulin&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to provide informed consent&#xD;
&#xD;
          -  Unable to comply with study procedures&#xD;
&#xD;
          -  Inadequate venous access as determined by study nurse or physician at time of&#xD;
             screening.&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  History of gastric banding, gastric bypass, or other gastrointestinal condition that&#xD;
             may prevent a subject from consuming a normal sized meal&#xD;
&#xD;
          -  Hemoglobin &lt;13.5 for men, &lt; 12 for women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <results_first_submitted>August 19, 2019</results_first_submitted>
  <results_first_submitted_qc>November 21, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">December 12, 2019</results_first_posted>
  <last_update_submitted>November 21, 2019</last_update_submitted>
  <last_update_submitted_qc>November 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Steven J. Russell, MD, PhD</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>29 enrolled in Multiplex PK profiling, 9 were ineligible. 21 completed.&#xD;
3 enrolled in the CIM arm of the trial. 2 completed, 1 was excluded from analysis.&#xD;
1 subject enrolled in both study phases. They completed the MultiPK profiling experiments, but were excluded from the CIM analysis.&#xD;
Total protocol enrollment was 33.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Multiplex Pharmacokinetic (PK) Profiling</title>
          <description>Multiplex pharmacokinetic profiling of regular human insulin, insulin aspart, insulin lispro, insulin glulisine, and regular human insulin&#xD;
Multiplex pharmacokinetic profiling</description>
        </group>
        <group group_id="P2">
          <title>Continuous Insulin Monitoring (CIM)</title>
          <description>Continuous insulin monitoring of insulin lispro&#xD;
Continuous insulin monitoring</description>
        </group>
        <group group_id="P3">
          <title>Multiplex PK Profiling and Continuous Insulin Monitoring</title>
          <description>Subjects that participated in both the multiplex PK profiling experiments and the continuous insulin monitoring experiments</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Inadequate Venous Access</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Principal Investigator Determination</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Excluded from Analysis</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Planning Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Multiplex Pharmacokinetic Profiling</title>
          <description>Multiplex pharmacokinetic profiling of regular human insulin, insulin aspart, insulin lispro, insulin glulisine, and regular human insulin&#xD;
Multiplex pharmacokinetic profiling</description>
        </group>
        <group group_id="B2">
          <title>Continuous Insulin Monitoring</title>
          <description>Continuous insulin monitoring of insulin lispro&#xD;
Continuous insulin monitoring</description>
        </group>
        <group group_id="B3">
          <title>Multiplex PK Profiling and Continuous Insulin Monitoring</title>
          <description>Participated in both study phases, the multiplex PK profiling visits and the CIM visits</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="29"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="1"/>
            <count group_id="B4" value="33"/>
          </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="47.09" spread="14.83"/>
                    <measurement group_id="B2" value="37.97" spread="26.40"/>
                    <measurement group_id="B3" value="74.65"/>
                    <measurement group_id="B4" value="47.09" spread="16.25"/>
                  </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="15"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>For Multiplex PK Profiling: Aggregate Mean Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax for Individuals</title>
        <description>The average difference in tmax between lispro and aspart in all participants</description>
        <time_frame>10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>All participants who completed the MultiPK visits</description>
          </group>
        </group_list>
        <measure>
          <title>For Multiplex PK Profiling: Aggregate Mean Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax for Individuals</title>
          <description>The average difference in tmax between lispro and aspart in all participants</description>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.28" spread="41.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin</title>
        <time_frame>10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose</time_frame>
        <population>Only 2 of the 4 experiments conducted under the Continuous Insulin Monitoring sub-study protocol produced usable data for analysis. Those two experiments are both reported here</population>
        <group_list>
          <group group_id="O1">
            <title>Experiment #3</title>
            <description>This includes the data from experiment #3. Only 2 of the 4 experiments conducted under the Continuous Insulin Monitoring sub-study protocol produced usable data for analysis. Those two experiments are both reported here.</description>
          </group>
          <group group_id="O2">
            <title>Experiment #4</title>
            <description>This includes the data from experiment #4. Only 2 of the 4 experiments conducted under the Continuous Insulin Monitoring sub-study protocol produced usable data for analysis. Those two experiments are both reported here.</description>
          </group>
        </group_list>
        <measure>
          <title>For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin</title>
          <population>Only 2 of the 4 experiments conducted under the Continuous Insulin Monitoring sub-study protocol produced usable data for analysis. Those two experiments are both reported here</population>
          <units>minutes</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Plasma insulin tmax</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                    <measurement group_id="O2" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CIM insulin tmax</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual</title>
        <description>Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average A1c for each of the three categories is reported.</description>
        <time_frame>Baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants Using the Faster Insulin</title>
            <description>Participants who were using the insulin analog at baseline that we determined had a faster tmax for this individual</description>
          </group>
          <group group_id="O2">
            <title>Participants Using the Slower Insulin</title>
            <description>Participants who were using the insulin analog at baseline that we determined had a slower tmax for this individual</description>
          </group>
          <group group_id="O3">
            <title>Participants Where the Two Insulins Were the Same</title>
            <description>Participants who we determined had no difference in the tmax between the two analogs</description>
          </group>
        </group_list>
        <measure>
          <title>Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual</title>
          <description>Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average A1c for each of the three categories is reported.</description>
          <units>percentage of glycosylated hemoglobin</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1" spread="1.1"/>
                    <measurement group_id="O2" value="8.6" spread="1.8"/>
                    <measurement group_id="O3" value="7.5" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Multiplex PK: Count of Subjects With Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax That is &gt; 25%</title>
        <time_frame>10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>All participants who completed the MultiPK visits</description>
          </group>
        </group_list>
        <measure>
          <title>Multiplex PK: Count of Subjects With Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax That is &gt; 25%</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog With Tmax &lt; 60 Minutes vs. Use of an Insulin Analog With Tmax &gt; 60 Minutes for Each Individual</title>
        <description>Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with tmax less than or equal to 60 minutes or using insulin with tmax &gt; 60 minutes. The average A1c per group is reported.</description>
        <time_frame>Baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subjects Using Insulin With a Tmax &lt; 60 Minutes</title>
            <description>Participants who were using the insulin analog at baseline that we determined had a tmax of less than 60 minutes for this individual.</description>
          </group>
          <group group_id="O2">
            <title>Subjects Using Insulin With a Tmax of &gt; 60 Minutes</title>
            <description>Participants who were using the insulin analog at baseline that we determined had a tmax of more than 60 minutes for this individual.</description>
          </group>
        </group_list>
        <measure>
          <title>Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog With Tmax &lt; 60 Minutes vs. Use of an Insulin Analog With Tmax &gt; 60 Minutes for Each Individual</title>
          <description>Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with tmax less than or equal to 60 minutes or using insulin with tmax &gt; 60 minutes. The average A1c per group is reported.</description>
          <units>percentage of glycosylated hemoglobin</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8" spread="1.2"/>
                    <measurement group_id="O2" value="7.3" spread="NA">Only one subject used an insulin analog at baseline that had a tmax &gt; 60 minutes, so no standard deviation calculation is possible</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Multiplex PK: Average Number of Hypoglycemia Events Over the Last Month at Baseline Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual</title>
        <description>Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average number of hypoglycemic events per month per group is reported.</description>
        <time_frame>1 month prior to study entry</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Participants Using the Faster Insulin</title>
            <description>Participants who were using the insulin analog at baseline that we determined had a faster tmax for this individual</description>
          </group>
          <group group_id="O2">
            <title>Participants Using the Slower Insulin</title>
            <description>Participants who were using the insulin analog at baseline that we determined had a slower tmax for this individual</description>
          </group>
          <group group_id="O3">
            <title>Participants Where the Two Insulins Were the Same</title>
            <description>Participants who we determined had no difference in the tmax between the two analogs</description>
          </group>
        </group_list>
        <measure>
          <title>Multiplex PK: Average Number of Hypoglycemia Events Over the Last Month at Baseline Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual</title>
          <description>Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average number of hypoglycemic events per month per group is reported.</description>
          <units>events in the month prior to study entry</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.6" spread="12.1"/>
                    <measurement group_id="O2" value="15.0" spread="15.6"/>
                    <measurement group_id="O3" value="13.1" spread="13.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>During the 5-hour in-clinic visits, visits occurred over the course of 1 year on average</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Multiplex Pharmacokinetic Profiling Only</title>
          <description>Multiplex pharmacokinetic profiling of regular human insulin, insulin aspart, insulin lispro, insulin glulisine, and regular human insulin. This only includes subjects that participated in the Multiplex PK profiling part of the protocol and not the continuous insulin monitoring part of the protocol.&#xD;
Multiplex pharmacokinetic profiling</description>
        </group>
        <group group_id="E2">
          <title>Continuous Insulin Monitoring Only</title>
          <description>Continuous insulin monitoring of insulin lispro. This only includes subjects that participated in the continuous insulin monitoring part of the protocol and did not participate in the Multiplex PK profiling part of the protocol.&#xD;
Continuous insulin monitoring</description>
        </group>
        <group group_id="E3">
          <title>Both Multiplex PK and Continuous Insulin Monitoring</title>
          <description>Participants that enrolled and completed both parts of the trial.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Courtney A Balliro</name_or_title>
      <organization>Massachusetts General Hospital</organization>
      <phone>617-726-1242</phone>
      <email>cballiro@partners.org</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/NCT01684943
org study id: 2010P001005
nct id: NCT01684943
lead sponsor: 
has dmc: Yes
The investigators are doing this research study to compare the pharmacokinetics (PK) (rate of
      absorption) of insulin lispro (Humalog), insulin aspart (Novolog), and insulin glulisine
      (Apidra) within individual subjects.

      Additionally, the investigators will perform a preliminary feasibility evaluation of a
      minimally invasive continuous insulin monitoring (CIM) device and its use to derive PK
      parameters in human subjects.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: All subjects participated in the single arm of the study. Some subjects participated in the continuous insulin monitoring sub-study in addition to the main protocol, or separate from the main protocol.
primary purpose: Treatment
masking: None (Open Label)
measure: For Multiplex PK Profiling: Aggregate Mean Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax for Individuals
time frame: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose
description: The average difference in tmax between lispro and aspart in all participants
measure: For Continuous Insulin Monitoring: Time to Maximum Plasma Insulin and Time to Maximum Continuous Insulin Monitoring Insulin
time frame: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose
measure: Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual
time frame: Baseline
description: Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average A1c for each of the three categories is reported.
measure: Multiplex PK: Count of Subjects With Difference in Tmax Between the Analog With Greatest and the Analog With the Least Value of Tmax That is > 25%
time frame: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 minutes after dose
measure: Multiplex PK: Average Baseline HbA1c Categorized According to Baseline Use of Insulin Analog With Tmax < 60 Minutes vs. Use of an Insulin Analog With Tmax > 60 Minutes for Each Individual
time frame: Baseline
description: Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with tmax less than or equal to 60 minutes or using insulin with tmax > 60 minutes. The average A1c per group is reported.
measure: Multiplex PK: Average Number of Hypoglycemia Events Over the Last Month at Baseline Categorized According to Baseline Use of Insulin Analog Found to Have the Most Favorable PK Profile for Each Individual
time frame: 1 month prior to study entry
description: Subjects with a difference in tmax between analogs will be categorized as follows: using insulin with best PK for them, using insulin with worst PK for them, or using insulin with intermediate PK for them. The average number of hypoglycemic events per month per group is reported.
arm group label: Multiplex pharmacokinetic profiling
arm group type: Experimental
description: Multiplex pharmacokinetic profiling of regular human insulin, insulin aspart, insulin lispro, insulin glulisine, and regular human insulin. All subjects participated in the single study arm and received injections of each type of insulin. Blood samples were drawn at intervals for pharmacokinetic profiling.
arm group label: Continuous insulin monitoring
arm group type: Experimental
description: Continuous insulin monitoring (CIM) of insulin lispro. Some subjects participated in the CIM sub-study, which is distinct from the Multiplex Pharmacokinetic Profiling study. This intervention involved administering insulin lispro and monitoring pharmacokinetic profile of the drug using blood samples and an investigational continuous insulin monitoring system.
intervention type: Other
intervention name: Multiplex pharmacokinetic profiling
arm group label: Multiplex pharmacokinetic profiling
intervention type: Other
intervention name: Continuous insulin monitoring
arm group label: Continuous insulin monitoring
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Steven J. Russell, MD, PhD
investigator title: Associate Professor
mesh term: Diabetes Mellitus, Type 1
mesh term: Insulin
sharing ipd: Yes
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 