<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/NCT03760640</url>
  </required_header>
  <id_info>
    <org_study_id>16917</org_study_id>
    <secondary_id>I8B-MC-ITSM</secondary_id>
    <nct_id>NCT03760640</nct_id>
  </id_info>
  <brief_title>A Study of LY900014 in a Medtronic Pump</brief_title>
  <official_title>Evaluation of LY900014 in a Medtronic Pump</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eli Lilly and Company</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>
      The purpose of this study is to compare the study drug LY900014 to insulin lispro (Humalog)&#xD;
      when both are delivered by the Medtronic MiniMed 670G System in adults with type 1 diabetes&#xD;
      (T1D). The study will consist of two treatment periods of 4 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 18, 2019</start_date>
  <completion_date type="Actual">October 7, 2019</completion_date>
  <primary_completion_date type="Actual">October 7, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Time With Sensor Glucose Values Between 70 and 180 Milligrams Per Deciliter (mg/dL) (24-Hour)</measure>
    <time_frame>Week 2 through Week 4</time_frame>
    <description>Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with baseline, period, sequence, strata (Hemoglobin A1c (HbA1c) [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Sensor Glucose Value (24-Hour)</measure>
    <time_frame>Week 2 through Week 4</time_frame>
    <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Time Spent in Auto Mode</measure>
    <time_frame>Week 2 through Week 4</time_frame>
    <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Time With Sensor Glucose Values &lt;54 mg/dL (24-Hour)</measure>
    <time_frame>Week 2 through Week 4</time_frame>
    <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Severe Hypoglycemic Events</measure>
    <time_frame>Week 2 through Week 4</time_frame>
    <description>Severe hypoglycemic is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience coma with or without seizures, and may require parenteral therapy. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group *36525. No severe hypoglycemia was reported for this study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Daily Insulin Dose</measure>
    <time_frame>Week 2 through Week 4</time_frame>
    <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Type1 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>LY900014</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 100 units per milliliter (U/mL) of LY900014 administered via continuous subcutaneous insulin infusion (CSII) by the Medtronic MiniMed 670G insulin pump.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Insulin Lispro (Humalog)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants received 100 U/mL of Insulin lispro (Humalog) administered via CSII by the Medtronic MiniMed 670G insulin pump.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY900014</intervention_name>
    <description>Administered SC</description>
    <arm_group_label>LY900014</arm_group_label>
    <other_name>Ultra-Rapid Lispro</other_name>
    <other_name>Lyumjev</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin Lispro</intervention_name>
    <description>Administered SC</description>
    <arm_group_label>Insulin Lispro (Humalog)</arm_group_label>
    <other_name>Humalog</other_name>
    <other_name>LY275585</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must have been diagnosed with type 1 diabetes and have been using insulin&#xD;
             continuously for at least 12 months&#xD;
&#xD;
          -  Participants must be using an insulin pump with &quot;rapid-acting insulin&quot; for at least 6&#xD;
             months and the same &quot;rapid acting insulin&quot; for at least the past 30 days&#xD;
&#xD;
          -  Participants must have hemoglobin A1c (HbA1c) values ≥6.0% and ≤8.0%&#xD;
&#xD;
          -  Participants must have been using the MiniMed 670G insulin pump for at least the past&#xD;
             90 days&#xD;
&#xD;
          -  Participants must use their Guardian (3) sensor at least an average of 75% of the time&#xD;
             and remain in Auto Mode an average of 70% of the time&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants must not have had more than 1 emergency treatment for very low blood&#xD;
             glucose or any hospitalizations for poor glucose control (very high blood sugar or&#xD;
             diabetic ketoacidosis) in the last 6 months&#xD;
&#xD;
          -  Participants must not have significant abnormal accumulation of fat, loss of fat&#xD;
             tissue, or scars just under the skin in areas of infusion or have a history of an&#xD;
             infection at an infusion site within 90 days prior to screening&#xD;
&#xD;
          -  Participants must not have a total daily insulin dose &gt;100 units&#xD;
&#xD;
          -  Participants must not be receiving any oral or injectable medication intended for the&#xD;
             treatment of diabetes other than rapid-acting analog insulin via CSII in the 30 days&#xD;
             prior to screening&#xD;
&#xD;
          -  Participants must not have major problems with their heart, kidneys, liver, or have a&#xD;
             blood disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)</last_name>
    <role>Study Director</role>
    <affiliation>Eli Lilly and Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Atlanta Diabetes Associates</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30318</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>International Diabetes Center</name>
      <address>
        <city>Saint Louis Park</city>
        <state>Minnesota</state>
        <zip>55416</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 15, 2019</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <results_first_submitted>October 2, 2020</results_first_submitted>
  <results_first_submitted_qc>October 2, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 29, 2020</results_first_posted>
  <last_update_submitted>October 2, 2020</last_update_submitted>
  <last_update_submitted_qc>October 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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 Lispro</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.</ipd_time_frame>
    <ipd_access_criteria>A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.</ipd_access_criteria>
    <ipd_url>http://www.clinicalstudydatarequest.com</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 13, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/40/NCT03760640/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 29, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/40/NCT03760640/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sequence 1</title>
          <description>Participants received 100 units per milliliter (U/mL) of LY900014 or Insulin lispro delivered via continuous subcutaneous insulin infusion (CSII) using the Medtronic MiniMed 670G insulin pump.&#xD;
Period 1: LY900014 Period 2: Insulin Lispro (Humalog)</description>
        </group>
        <group group_id="P2">
          <title>Sequence 2</title>
          <description>Participants received 100 U/mL of LY900014 or Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.&#xD;
Period 1: Insulin Lispro (Humalog) Period 2: LY900014</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All randomized participants who received at least one dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Sequence 1</title>
          <description>Participants received 100 units per milliliter (U/mL) of LY900014 or Humalog delivered via continuous subcutaneous insulin infusion (CSII) using the Medtronic MiniMed 670G insulin pump.&#xD;
Period 1: LY900014 Period 2: Humalog</description>
        </group>
        <group group_id="B2">
          <title>Sequence 2</title>
          <description>Participants received 100 U/mL of LY900014 or Humalog delivered via CSII using the Medtronic MiniMed 670G insulin pump.&#xD;
Period 1: Humalog Period 2: LY900014</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="20"/>
            <count group_id="B2" value="22"/>
            <count group_id="B3" value="42"/>
          </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="47.5" spread="14.9"/>
                    <measurement group_id="B2" value="48.1" spread="13.1"/>
                    <measurement group_id="B3" value="47.8" spread="13.8"/>
                  </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="12"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Time With Sensor Glucose Values Between 70 and 180 Milligrams Per Deciliter (mg/dL) (24-Hour)</title>
        <description>Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with baseline, period, sequence, strata (Hemoglobin A1c (HbA1c) [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
        <time_frame>Week 2 through Week 4</time_frame>
        <population>All randomized participants who received at least one dose of study drug and had at least one post-baseline data.</population>
        <group_list>
          <group group_id="O1">
            <title>LY900014</title>
            <description>Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Lispro (Humalog)</title>
            <description>Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Time With Sensor Glucose Values Between 70 and 180 Milligrams Per Deciliter (mg/dL) (24-Hour)</title>
          <description>Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with baseline, period, sequence, strata (Hemoglobin A1c (HbA1c) [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
          <population>All randomized participants who received at least one dose of study drug and had at least one post-baseline data.</population>
          <units>Percentage of Time</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="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.98" spread="0.857"/>
                    <measurement group_id="O2" value="77.84" spread="0.857"/>
                  </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</non_inferiority_type>
            <p_value>0.339</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.86</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.35</ci_lower_limit>
            <ci_upper_limit>0.63</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Sensor Glucose Value (24-Hour)</title>
        <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
        <time_frame>Week 2 through Week 4</time_frame>
        <population>All randomized participants who received at least one dose of study drug and had at least one post-baseline data.</population>
        <group_list>
          <group group_id="O1">
            <title>LY900014</title>
            <description>Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Lispro (Humalog)</title>
            <description>Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Sensor Glucose Value (24-Hour)</title>
          <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
          <population>All randomized participants who received at least one dose of study drug and had at least one post-baseline data.</population>
          <units>milligrams per deciliter (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="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="148.64" spread="1.193"/>
                    <measurement group_id="O2" value="145.64" spread="1.193"/>
                  </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</non_inferiority_type>
            <p_value>0.011</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>3.00</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.10</ci_lower_limit>
            <ci_upper_limit>4.90</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Time Spent in Auto Mode</title>
        <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
        <time_frame>Week 2 through Week 4</time_frame>
        <population>All randomized participants who received at least one dose of study drug and had at least post-baseline data.</population>
        <group_list>
          <group group_id="O1">
            <title>LY900014</title>
            <description>Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Lispro (Humalog)</title>
            <description>Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Time Spent in Auto Mode</title>
          <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
          <population>All randomized participants who received at least one dose of study drug and had at least post-baseline data.</population>
          <units>Percentage of Time</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="42"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.98" spread="0.829"/>
                    <measurement group_id="O2" value="91.42" spread="0.838"/>
                  </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</non_inferiority_type>
            <p_value>0.557</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.56</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.02</ci_lower_limit>
            <ci_upper_limit>2.14</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Time With Sensor Glucose Values &lt;54 mg/dL (24-Hour)</title>
        <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
        <time_frame>Week 2 through Week 4</time_frame>
        <population>All randomized participants who received at least one dose of study drug and had at least one post-baseline data.</population>
        <group_list>
          <group group_id="O1">
            <title>LY900014</title>
            <description>Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Lispro (Humalog)</title>
            <description>Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Time With Sensor Glucose Values &lt;54 mg/dL (24-Hour)</title>
          <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
          <population>All randomized participants who received at least one dose of study drug and had at least one post-baseline data.</population>
          <units>Percentage of Time</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="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.34" spread="0.067"/>
                    <measurement group_id="O2" value="0.38" spread="0.067"/>
                  </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</non_inferiority_type>
            <p_value>0.548</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.04</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.15</ci_lower_limit>
            <ci_upper_limit>0.07</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Severe Hypoglycemic Events</title>
        <description>Severe hypoglycemic is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience coma with or without seizures, and may require parenteral therapy. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group *36525. No severe hypoglycemia was reported for this study.</description>
        <time_frame>Week 2 through Week 4</time_frame>
        <population>All randomized participants with evaluable hypoglycemic data.</population>
        <group_list>
          <group group_id="O1">
            <title>LY900014</title>
            <description>Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Lispro (Humalog)</title>
            <description>Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Severe Hypoglycemic Events</title>
          <description>Severe hypoglycemic is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience coma with or without seizures, and may require parenteral therapy. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group *36525. No severe hypoglycemia was reported for this study.</description>
          <population>All randomized participants with evaluable hypoglycemic data.</population>
          <units>Events/Participant/100 Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Daily Insulin Dose</title>
        <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
        <time_frame>Week 2 through Week 4</time_frame>
        <population>All randomized participants who received at least one dose of study drug and had at least one post-baseline data.</population>
        <group_list>
          <group group_id="O1">
            <title>LY900014</title>
            <description>Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Lispro (Humalog)</title>
            <description>Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Daily Insulin Dose</title>
          <description>LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [&lt;=7.0%, &gt;7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [&lt;=75%, &gt;75%]), treatment (Type III sum of squares) as fixed factors.</description>
          <population>All randomized participants who received at least one dose of study drug and had at least one post-baseline data.</population>
          <units>Units (U)/day</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="42"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.59" spread="1.023"/>
                    <measurement group_id="O2" value="42.10" spread="1.023"/>
                  </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</non_inferiority_type>
            <p_value>0.577</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.49</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.97</ci_lower_limit>
            <ci_upper_limit>1.94</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up To 10 Weeks</time_frame>
      <desc>All randomized participants who received at least one dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>LY900014</title>
          <description>Participants received 100 U/mL of LY900014 delivered via CSII using the Medtronic MiniMed 670G insulin pump.</description>
        </group>
        <group group_id="E2">
          <title>Insulin Lispro (Humalog)</title>
          <description>Participants received 100 U/mL of Insulin lispro delivered via CSII using the Medtronic MiniMed 670G insulin pump.</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="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 22.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Infusion site pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="42"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Medical Officer</name_or_title>
      <organization>Eli Lilly and Company</organization>
      <phone>800-545-5979</phone>
      <email>ClinicalTrials.gov@lilly.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/NCT03760640
org study id: 16917
secondary id: I8B-MC-ITSM
nct id: NCT03760640
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to compare the study drug LY900014 to insulin lispro (Humalog)
      when both are delivered by the Medtronic MiniMed 670G System in adults with type 1 diabetes
      (T1D). The study will consist of two treatment periods of 4 weeks.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of Time With Sensor Glucose Values Between 70 and 180 Milligrams Per Deciliter (mg/dL) (24-Hour)
time frame: Week 2 through Week 4
description: Least Square (LS) mean was determined by mixed-model repeated measures (MMRM) with baseline, period, sequence, strata (Hemoglobin A1c (HbA1c) [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.
measure: Mean Sensor Glucose Value (24-Hour)
time frame: Week 2 through Week 4
description: LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.
measure: Percentage of Time Spent in Auto Mode
time frame: Week 2 through Week 4
description: LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.
measure: Percentage of Time With Sensor Glucose Values <54 mg/dL (24-Hour)
time frame: Week 2 through Week 4
description: LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.
measure: Rate of Severe Hypoglycemic Events
time frame: Week 2 through Week 4
description: Severe hypoglycemic is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience coma with or without seizures, and may require parenteral therapy. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group *36525. No severe hypoglycemia was reported for this study.
measure: Total Daily Insulin Dose
time frame: Week 2 through Week 4
description: LS mean was determined by MMRM with baseline, period, sequence, strata (HbA1c [<=7.0%, >7.0%] and percentage of time with sensor glucose values from 70 to 180 mg/dL over the 2 weeks prior to randomization [<=75%, >75%]), treatment (Type III sum of squares) as fixed factors.
arm group label: LY900014
arm group type: Experimental
description: Participants received 100 units per milliliter (U/mL) of LY900014 administered via continuous subcutaneous insulin infusion (CSII) by the Medtronic MiniMed 670G insulin pump.
arm group label: Insulin Lispro (Humalog)
arm group type: Active Comparator
description: Participants received 100 U/mL of Insulin lispro (Humalog) administered via CSII by the Medtronic MiniMed 670G insulin pump.
intervention type: Drug
intervention name: LY900014
description: Administered SC
arm group label: LY900014
other name: Ultra-Rapid Lispro
other name: Lyumjev
intervention type: Drug
intervention name: Insulin Lispro
description: Administered SC
arm group label: Insulin Lispro (Humalog)
other name: Humalog
other name: LY275585
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: Study Director
affiliation: Eli Lilly and Company
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 1
mesh term: Insulin Lispro
sharing ipd: Yes
ipd description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
ipd access criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
ipd url: http://www.clinicalstudydatarequest.com
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 