<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/NCT03232983</url>
  </required_header>
  <id_info>
    <org_study_id>16639</org_study_id>
    <secondary_id>I8B-MC-ITRT</secondary_id>
    <nct_id>NCT03232983</nct_id>
  </id_info>
  <brief_title>A Study of LY900014 Formulation at Different Injection Sites in Healthy Participants</brief_title>
  <official_title>Effect of Injection Site on the Relative and Absolute Bioavailability of Single Dose of LY900014 in Healthy Subjects</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates a new formulation of insulin lispro, LY900014, a drug that lowers blood&#xD;
      sugar. It is administered by injection into the vein and under the skin of the abdomen, thigh&#xD;
      and arm.&#xD;
&#xD;
      The study will be conducted in healthy people to investigate the effect of different&#xD;
      injection sites on the amount of insulin lispro in the bloodstream.&#xD;
&#xD;
      Side effects and tolerability will be documented. The study will last for about 10 weeks for&#xD;
      each participant, including screening and follow up. Screening is required within 28 days&#xD;
      prior to entering the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 14, 2017</start_date>
  <completion_date type="Actual">November 9, 2017</completion_date>
  <primary_completion_date type="Actual">November 9, 2017</primary_completion_date>
  <phase>Phase 1</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration</measure>
    <time_frame>Day 1: Pre-dose, 2.5, 5, 10, 15, 20, 25, 30, 40, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose</time_frame>
    <description>Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose [AUC(0-10h)].</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure</measure>
    <time_frame>Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 120 to 480 minutes and every 10 minutes for 480 to 600 minutes post-dose</time_frame>
    <description>Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure. During the euglycemic clamp procedure, blood glucose concentrations are held constant after the administration of LY900014 by adjusting the exogenous glucose infusion rate.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>LY900014 (SC Abdomen)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of 15-U of LY900014 administered subcutaneously (SC) into the abdomen in one period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LY900014 (SC Thigh)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of 15-U of LY900014 administered SC into the thigh in one period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LY900014 (SC Arm)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of 15-U of LY900014 administered SC into the arm (deltoid) in one period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LY900014 (IV)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single dose of 15-U of LY900014 administered intravenously (IV) in one period</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY900014 (SC)</intervention_name>
    <description>Administered SC</description>
    <arm_group_label>LY900014 (SC Abdomen)</arm_group_label>
    <arm_group_label>LY900014 (SC Arm)</arm_group_label>
    <arm_group_label>LY900014 (SC Thigh)</arm_group_label>
    <other_name>Ultra-Rapid Lispro</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY900014 (IV)</intervention_name>
    <description>Administered IV</description>
    <arm_group_label>LY900014 (IV)</arm_group_label>
    <other_name>Ultra-Rapid Lispro</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Overtly healthy male or a female (not pregnant and agreeable to take birth control&#xD;
             measures until study completion)&#xD;
&#xD;
          -  Have a body mass index (BMI) of 18 to 30 kilogram per square meter (kg/m²)&#xD;
&#xD;
          -  Have normal blood pressure, pulse rate, electrocardiogram (ECG), blood and urine&#xD;
             laboratory test results that are acceptable for the study&#xD;
&#xD;
          -  Are nonsmokers, have not smoked for at least 6 months prior to entering the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Are currently participating in or completed a clinical trial within the last 30 days&#xD;
             or any other type of medical research judged to be incompatible with this study&#xD;
&#xD;
          -  Have previously participated or withdrawn from this study&#xD;
&#xD;
          -  Had blood loss of more than 450 milliliters (mL) within the last 3 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</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>For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.</name>
      <address>
        <city>Singapore</city>
        <zip>117597</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <results_first_submitted>April 20, 2020</results_first_submitted>
  <results_first_submitted_qc>April 20, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 30, 2020</results_first_posted>
  <last_update_submitted>April 20, 2020</last_update_submitted>
  <last_update_submitted_qc>April 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 30, 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 2</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>
  <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>July 14, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03232983/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>August 4, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03232983/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>This is an open-label, randomized, crossover, up to 10-hour euglycemic clamp study in which participants were randomized into one of four treatment sequences. Participants received single doses of 15 units of LY900014 on 4 occasions (treatment Periods 1 through 4) with a wash-out period of at least 3 days between study drug administration.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>LY900014 Treatment Sequence 1: Abdomen,Thigh, Deltoid(Arm), IV</title>
          <description>Single dose of 15-U of LY900014 administered subcutaneously (SC) into the abdomen in Period 1, Thigh in Period 2, Deltoid (Arm) in Period 3, and single 15-U intravenous (IV) bolus injection in Period 4.</description>
        </group>
        <group group_id="P2">
          <title>LY900014 Treatment Sequence 2: Deltoid, Abdomen, IV, Thigh</title>
          <description>Single dose of 15-U of LY900014 administered SC into the: Deltoid in Period 1, Abdomen in Period 2, single 15-U IV bolus injection in Period 3, and single 15-U SC administration into the Thigh in Period 4.</description>
        </group>
        <group group_id="P3">
          <title>LY900014 Treatment Sequence 3: IV, Deltoid, Thigh, Abdomen</title>
          <description>Single 15-U IV bolus injection of LY900014 administered in Period 1, single 15-U dose administered SC in the Deltoid in Period 2, Thigh in Period 3, and Abdomen in Period 4.</description>
        </group>
        <group group_id="P4">
          <title>LY900014 Treatment Sequence 4: Thigh, IV, Abdomen, Deltoid</title>
          <description>Single dose of 15-U of LY900014 administered SC in Thigh in Period 1, single 15-U IV bolus injection in Period 2, single dose of 15-U administered SC in the Abdomen in Period 3, and Deltoid in Period 4.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least One Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Washout Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" 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="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 3</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout Period 3</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Period 4</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants.</population>
      <group_list>
        <group group_id="B1">
          <title>Overall</title>
          <description>Single 15-U dose of LY900014 administered in treatment Period 1- 4, as SC injection into the abdomen, the thigh, the deltoid or an IV bolus injection, per randomized treatment sequence.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="28"/>
          </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="39.8" spread="8.6"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </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_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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>Singapore</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kilograms (kg)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.11" spread="10.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration</title>
        <description>Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose [AUC(0-10h)].</description>
        <time_frame>Day 1: Pre-dose, 2.5, 5, 10, 15, 20, 25, 30, 40, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose</time_frame>
        <population>All participants who have received at least one dose of study drug and have measurable insulin lispro concentrations and evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>LY900014 (SC Abdomen)</title>
            <description>Single 15-U dose of LY900014 administered subcutaneously (SC) into the abdomen in one period.</description>
          </group>
          <group group_id="O2">
            <title>LY900014 (SC Deltoid)</title>
            <description>Single 15-U dose of LY900014 administered SC into the deltoid in one period.</description>
          </group>
          <group group_id="O3">
            <title>LY900014 (IV)</title>
            <description>Single 15-U injection IV bolus of LY900014 administered in one period.</description>
          </group>
          <group group_id="O4">
            <title>LY900014 (SC Thigh)</title>
            <description>Single 15-U dose of LY900014 administered SC into the thigh in one period.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration</title>
          <description>Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose [AUC(0-10h)].</description>
          <population>All participants who have received at least one dose of study drug and have measurable insulin lispro concentrations and evaluable PK data.</population>
          <units>picomole * hour/Liter (pmol * hr/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
                <count group_id="O3" value="27"/>
                <count group_id="O4" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1760" spread="20"/>
                    <measurement group_id="O2" value="1800" spread="16"/>
                    <measurement group_id="O3" value="2770" spread="22"/>
                    <measurement group_id="O4" value="1750" spread="19"/>
                  </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>
            <groups_desc>Geometric Least Squares Means (LSMeans) were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio of Geometric Least Squares Means</param_type>
            <param_value>1.03</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.992</ci_lower_limit>
            <ci_upper_limit>1.07</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio of Geometric Least Squares Means</param_type>
            <param_value>1.00</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.962</ci_lower_limit>
            <ci_upper_limit>1.04</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure</title>
        <description>Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure. During the euglycemic clamp procedure, blood glucose concentrations are held constant after the administration of LY900014 by adjusting the exogenous glucose infusion rate.</description>
        <time_frame>Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 120 to 480 minutes and every 10 minutes for 480 to 600 minutes post-dose</time_frame>
        <population>All participants who have received at least one dose of study drug administered and have completed at least one clamp procedure. The IV treatment arm was needed only for PK as it served as the reference to determine the absolute bioavailability.</population>
        <group_list>
          <group group_id="O1">
            <title>LY900014 (SC Abdomen)</title>
            <description>Single 15-U dose of LY900014 administered subcutaneously (SC) into the abdomen in one period.</description>
          </group>
          <group group_id="O2">
            <title>LY900014 (SC Deltoid)</title>
            <description>Single 15-U dose of LY900014 administered SC into the arm in one period.</description>
          </group>
          <group group_id="O3">
            <title>LY900014 (SC Thigh)</title>
            <description>Single 15-U dose of LY900014 administered SC into the thigh in one period.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure</title>
          <description>Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure. During the euglycemic clamp procedure, blood glucose concentrations are held constant after the administration of LY900014 by adjusting the exogenous glucose infusion rate.</description>
          <population>All participants who have received at least one dose of study drug administered and have completed at least one clamp procedure. The IV treatment arm was needed only for PK as it served as the reference to determine the absolute bioavailability.</population>
          <units>milligram per kilogram (mg/kg)</units>
          <param>Geometric Least Squares Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
                <count group_id="O3" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1490" spread="45"/>
                    <measurement group_id="O2" value="1630" spread="50"/>
                    <measurement group_id="O3" value="1730" spread="38"/>
                  </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>
            <groups_desc>Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio of Geometric LSMeans</param_type>
            <param_value>1.09</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.00</ci_lower_limit>
            <ci_upper_limit>1.20</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Geometric LSMeans were controlled for injection site, study period, and sequence as fixed effects, and subject within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Ratio of Geometric LSMeans</param_type>
            <param_value>1.14</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.04</ci_lower_limit>
            <ci_upper_limit>1.25</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline to end of study (up to 49 days)</time_frame>
      <desc>All participants who received at least one dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>15-U LY900014 Abdomen</title>
          <description>Single dose of 15-U of LY900014 administered subcutaneously (SC) into the abdomen.</description>
        </group>
        <group group_id="E2">
          <title>15-U LY900014 Thigh</title>
          <description>Single dose of 15-U of LY900014 administered SC into the Thigh.</description>
        </group>
        <group group_id="E3">
          <title>15-U LY900014 Deltoid</title>
          <description>Single dose of 15-U of LY900014 administered SC into the Deltoid.</description>
        </group>
        <group group_id="E4">
          <title>15-U LY900014 IV</title>
          <description>Single 15-U LY900014 administered IV bolus injection.</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="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.0</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="6" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="26"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Application site erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Catheter site bruise</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Catheter site erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Catheter site swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Infusion site erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Infusion site pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Infusion site swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Vessel puncture site bruise</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Vessel puncture site pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </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>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/NCT03232983
org study id: 16639
secondary id: I8B-MC-ITRT
nct id: NCT03232983
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study evaluates a new formulation of insulin lispro, LY900014, a drug that lowers blood
      sugar. It is administered by injection into the vein and under the skin of the abdomen, thigh
      and arm.

      The study will be conducted in healthy people to investigate the effect of different
      injection sites on the amount of insulin lispro in the bloodstream.

      Side effects and tolerability will be documented. The study will last for about 10 weeks for
      each participant, including screening and follow up. Screening is required within 28 days
      prior to entering the study.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Pharmacokinetics: Insulin Lispro Area Under the Concentration Versus Time Curve (AUC) Following LY900014 Administration
time frame: Day 1: Pre-dose, 2.5, 5, 10, 15, 20, 25, 30, 40, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose
description: Pharmacokinetics(PK): Insulin lispro AUC from time zero to 10 hours post dose [AUC(0-10h)].
measure: Total Amount of Glucose Infused (Gtot) Over Duration of the Clamp Procedure
time frame: Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 120 to 480 minutes and every 10 minutes for 480 to 600 minutes post-dose
description: Glucodynamics: Gtot is the total glucose infusion over the clamp duration (10 hours) and is used to measure the study drug action over time as measured by the euglycemic clamp procedure. During the euglycemic clamp procedure, blood glucose concentrations are held constant after the administration of LY900014 by adjusting the exogenous glucose infusion rate.
arm group label: LY900014 (SC Abdomen)
arm group type: Experimental
description: Single dose of 15-U of LY900014 administered subcutaneously (SC) into the abdomen in one period
arm group label: LY900014 (SC Thigh)
arm group type: Experimental
description: Single dose of 15-U of LY900014 administered SC into the thigh in one period
arm group label: LY900014 (SC Arm)
arm group type: Experimental
description: Single dose of 15-U of LY900014 administered SC into the arm (deltoid) in one period
arm group label: LY900014 (IV)
arm group type: Active Comparator
description: Single dose of 15-U of LY900014 administered intravenously (IV) in one period
intervention type: Drug
intervention name: LY900014 (SC)
description: Administered SC
arm group label: LY900014 (SC Abdomen)
arm group label: LY900014 (SC Arm)
arm group label: LY900014 (SC Thigh)
other name: Ultra-Rapid Lispro
intervention type: Drug
intervention name: LY900014 (IV)
description: Administered IV
arm group label: LY900014 (IV)
other name: Ultra-Rapid Lispro
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
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: 
country: Singapore
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin Lispro
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 