<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/NCT01688635</url>
  </required_header>
  <id_info>
    <org_study_id>14973</org_study_id>
    <secondary_id>I4L-MC-ABEO</secondary_id>
    <nct_id>NCT01688635</nct_id>
  </id_info>
  <brief_title>A Study to Compare LY2963016 and US-approved Lantus® After Single Dose Administration to Healthy Participants</brief_title>
  <official_title>Comparative Pharmacokinetics and Pharmacodynamics of LY2963016 and US-Approved Lantus® After Single-Dose Subcutaneous Administration to 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the pharmacokinetics and pharmacodynamics of&#xD;
      LY2963016 and US-approved Lantus®. The study involves four single injections; two doses of&#xD;
      LY2963016 and two doses of US-approved Lantus®. The study will have 4 periods. In each&#xD;
      period, a single injection will be administered before undergoing a euglycemic clamp that&#xD;
      lasts for 24 hours. There will be at least a 7 day washout between each period. Side effects&#xD;
      will be documented. Study participation is expected to last up to 14 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">February 2013</completion_date>
  <primary_completion_date type="Actual">February 2013</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus</measure>
    <time_frame>30 minutes predose up to 24 hours postdose in all treatment periods</time_frame>
    <description>The AUC from time 0 to 24 hours (AUC0-24) of LY2963016 and US-Approved Lantus was measured.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus</measure>
    <time_frame>30 minutes predose up to 24 hours postdose in all treatment periods</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Glucose Infusion Rate (Rmax)</measure>
    <time_frame>30 minutes predose up to 24 hours postdose in all treatment periods</time_frame>
    <description>Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain target blood glucose level and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure</measure>
    <time_frame>30 minutes predose up to 24 hours postdose in all treatment periods</time_frame>
    <description>Gtot was the total glucose infusion over the clamp duration and was used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations were held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">91</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>LY2963016</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single 0.5 units per kilogram (U/kg) dose of LY2963016 administered subcutaneously, twice during the study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>US-approved Lantus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single 0.5 U/kg dose of US-approved Lantus administered subcutaneously, twice during the study</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY2963016</intervention_name>
    <description>Administered subcutaneously</description>
    <arm_group_label>LY2963016</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>US Approved Lantus</intervention_name>
    <description>Administered subcutaneously</description>
    <arm_group_label>US-approved Lantus</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Are overtly healthy males or females&#xD;
&#xD;
          -  Have body mass index between 18.5 and 29.9 kilograms per meter square (kg/m^2)&#xD;
&#xD;
          -  Are nonsmokers and have not smoked for at least 2 months prior to entering the study&#xD;
&#xD;
          -  Have normal blood pressure and pulse rates at screening&#xD;
&#xD;
          -  Have electrocardiograms (ECGs) at screening considered as within normal limits&#xD;
&#xD;
          -  Have clinical laboratory test results within normal reference ranges&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Are currently enrolled in or discontinued within the last 30 days from a clinical&#xD;
             study involving an investigational drug or device or are concurrently enrolled in any&#xD;
             other type of medical research&#xD;
&#xD;
          -  Have known allergies to insulin, its excipients, or related drugs or have history of&#xD;
             relevant allergic reactions of any origin&#xD;
&#xD;
          -  Have significant history of or current cardiovascular, respiratory, hepatic, renal,&#xD;
             gastrointestinal, endocrine, hematological, or neurological disorders&#xD;
&#xD;
          -  Show evidence of significant active neuropsychiatric disease, including taking&#xD;
             prescription medication for such diseases&#xD;
&#xD;
          -  Show evidence of current use of known drugs of abuse or a history of use within the&#xD;
             past year&#xD;
&#xD;
          -  Have a history of first-degree relatives known to have diabetes mellitus&#xD;
&#xD;
          -  Show evidence of human immunodeficiency virus (HIV) infection and/or positive human&#xD;
             HIV antibodies at screening&#xD;
&#xD;
          -  Have positive hepatitis B surface antigen at screening&#xD;
&#xD;
          -  Intend to use over-the-counter or prescription medication within 7 or 14 days,&#xD;
             respectively, prior to dosing (apart from vitamin/mineral supplements, occasional&#xD;
             paracetamol, thyroid replacement medication, or birth control methods)&#xD;
&#xD;
          -  Have donated or had a blood loss of 450 milliliters (mL) within 3 months prior to&#xD;
             study enrollment&#xD;
&#xD;
          -  Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14&#xD;
             units per week (females) or are unwilling to stop alcohol consumption from 24 hours&#xD;
             prior to each dosing until discharged from the clinical research unit (CRU)&#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 from 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>October 2014</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <results_first_submitted>October 3, 2014</results_first_submitted>
  <results_first_submitted_qc>October 3, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 7, 2014</results_first_posted>
  <last_update_submitted>October 3, 2014</last_update_submitted>
  <last_update_submitted_qc>October 3, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 7, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Volunteers</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Glargine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>The study comprised 2 sequences with 4 treatment periods. Participants were randomly assigned to 1 of the 2 sequences.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>LY/Lantus/LY/Lantus</title>
          <description>A single 0.5-units/kilogram (U/kg) dose of LY2963016 (LY) administered subcutaneously during Periods 1 and 3.&#xD;
A single 0.5-U/kg dose of US-approved Lantus (Lantus) administered subcutaneously during Periods 2 and 4.&#xD;
There was at least a 7-day washout between treatment periods.</description>
        </group>
        <group group_id="P2">
          <title>Lantus/LY/Lantus/LY</title>
          <description>A single 0.5-U/kg dose of US-approved Lantus administered subcutaneously during Periods 1 and 3.&#xD;
A single 0.5-U/kg dose of LY2963016 administered subcutaneously during Periods 2 and 4.&#xD;
There was at least a 7-day washout between treatment periods.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="46"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="46"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="46"/>
              </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>Washout 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="46"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </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_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="44"/>
              </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>Washout 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
                <participants group_id="P2" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Sponsor Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 3</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
                <participants group_id="P2" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
                <participants group_id="P2" count="42"/>
              </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>Washout 3</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
                <participants group_id="P2" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" 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_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 4</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="42"/>
              </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</population>
      <group_list>
        <group group_id="B1">
          <title>LY2963016 and US-approved Lantus</title>
          <description>Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study; Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study. There was at least a 7-day washout between treatment periods.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="91"/>
          </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="32.7" spread="9.0"/>
                  </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="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Singapore</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus</title>
        <description>The AUC from time 0 to 24 hours (AUC0-24) of LY2963016 and US-Approved Lantus was measured.</description>
        <time_frame>30 minutes predose up to 24 hours postdose in all treatment periods</time_frame>
        <population>Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable PK data to calculate AUC(0-24). Participants were analyzed based on the treatment they received.</population>
        <group_list>
          <group group_id="O1">
            <title>LY2963016</title>
            <description>Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study. There was at least a 7-day washout between treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>US-approved Lantus</title>
            <description>Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study.&#xD;
There was at least a 7-day washout between treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus</title>
          <description>The AUC from time 0 to 24 hours (AUC0-24) of LY2963016 and US-Approved Lantus was measured.</description>
          <population>Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable PK data to calculate AUC(0-24). Participants were analyzed based on the treatment they received.</population>
          <units>picomoles*hour/liter (pmol*h/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="87"/>
                <count group_id="O2" value="89"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1720" spread="42"/>
                    <measurement group_id="O2" value="1900" spread="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus</title>
        <time_frame>30 minutes predose up to 24 hours postdose in all treatment periods</time_frame>
        <population>Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable PK data to calculate Cmax. Participants were analyzed based on the treatment they received</population>
        <group_list>
          <group group_id="O1">
            <title>LY2963016</title>
            <description>Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study.&#xD;
There was at least a 7-day washout between treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>US-approved Lantus</title>
            <description>Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study.&#xD;
There was at least a 7-day washout between treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus</title>
          <population>Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable PK data to calculate Cmax. Participants were analyzed based on the treatment they received</population>
          <units>picomoles/liter (pmol/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="88"/>
                <count group_id="O2" value="89"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="103" spread="41"/>
                    <measurement group_id="O2" value="111" spread="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Glucose Infusion Rate (Rmax)</title>
        <description>Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain target blood glucose level and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.</description>
        <time_frame>30 minutes predose up to 24 hours postdose in all treatment periods</time_frame>
        <population>Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data to calculate Rmax. Participants were analyzed based on the treatment they received.</population>
        <group_list>
          <group group_id="O1">
            <title>LY2963016</title>
            <description>Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study.&#xD;
There was at least a 7-day washout between treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>US-approved Lantus</title>
            <description>Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study.&#xD;
There was at least a 7-day washout between treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Glucose Infusion Rate (Rmax)</title>
          <description>Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain target blood glucose level and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.</description>
          <population>Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data to calculate Rmax. Participants were analyzed based on the treatment they received.</population>
          <units>milligrams/kilograms/minute (mg/kg/min)</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="88"/>
                <count group_id="O2" value="88"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.12" spread="54"/>
                    <measurement group_id="O2" value="2.27" spread="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure</title>
        <description>Gtot was the total glucose infusion over the clamp duration and was used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations were held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.</description>
        <time_frame>30 minutes predose up to 24 hours postdose in all treatment periods</time_frame>
        <population>Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data to calculate Gtot. Participants were analyzed based on the treatment they received.</population>
        <group_list>
          <group group_id="O1">
            <title>LY2963016</title>
            <description>Single 0.5-units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study.&#xD;
There was at least a 7-day washout between treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>US-approved Lantus</title>
            <description>Single 0.5-U/kg dose of US-approved Lantus administered subcutaneously twice during the study.&#xD;
There was at least a 7-day washout between treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure</title>
          <description>Gtot was the total glucose infusion over the clamp duration and was used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations were held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.</description>
          <population>Full analysis set (FAS): All randomized participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data to calculate Gtot. Participants were analyzed based on the treatment they received.</population>
          <units>milligrams/kilogram (mg/kg)</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="88"/>
                <count group_id="O2" value="88"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1670" spread="60"/>
                    <measurement group_id="O2" value="1820" spread="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Randomization to study completion</time_frame>
      <desc>Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.</desc>
      <group_list>
        <group group_id="E1">
          <title>LY2963016</title>
          <description>Single 0.5 units per kilogram (U/kg) dose of LY2963016 administered subcutaneously twice during the study.&#xD;
There was at least a 7-day washout between the treatment periods.</description>
        </group>
        <group group_id="E2">
          <title>US-approved Lantus</title>
          <description>Single 0.5 U/kg dose of US-approved Lantus administered subcutaneously twice during the study.&#xD;
There was at least a 7-day washout between the treatment periods.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="89"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>4</frequency_threshold>
        <default_vocab>MedDRA 15.0</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="42" subjects_at_risk="89"/>
                <counts group_id="E2" subjects_affected="42" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site haematoma</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="89"/>
                <counts group_id="E2" events="11" subjects_affected="9" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="89"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Catheter site swelling</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="89"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Infusion site pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="89"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Infusion site swelling</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="89"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="90"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="89"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural site reaction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="89"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="89"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="90"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="89"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="90"/>
              </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>
    </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/NCT01688635
org study id: 14973
secondary id: I4L-MC-ABEO
nct id: NCT01688635
lead sponsor: 
has dmc: No
The purpose of this study is to compare the pharmacokinetics and pharmacodynamics of
      LY2963016 and US-approved Lantus®. The study involves four single injections; two doses of
      LY2963016 and two doses of US-approved Lantus®. The study will have 4 periods. In each
      period, a single injection will be administered before undergoing a euglycemic clamp that
      lasts for 24 hours. There will be at least a 7 day washout between each period. Side effects
      will be documented. Study participation is expected to last up to 14 weeks.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus
time frame: 30 minutes predose up to 24 hours postdose in all treatment periods
description: The AUC from time 0 to 24 hours (AUC0-24) of LY2963016 and US-Approved Lantus was measured.
measure: Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus
time frame: 30 minutes predose up to 24 hours postdose in all treatment periods
measure: Maximum Glucose Infusion Rate (Rmax)
time frame: 30 minutes predose up to 24 hours postdose in all treatment periods
description: Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain target blood glucose level and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.
measure: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure
time frame: 30 minutes predose up to 24 hours postdose in all treatment periods
description: Gtot was the total glucose infusion over the clamp duration and was used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations were held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.
arm group label: LY2963016
arm group type: Experimental
description: Single 0.5 units per kilogram (U/kg) dose of LY2963016 administered subcutaneously, twice during the study
arm group label: US-approved Lantus
arm group type: Experimental
description: Single 0.5 U/kg dose of US-approved Lantus administered subcutaneously, twice during the study
intervention type: Drug
intervention name: LY2963016
description: Administered subcutaneously
arm group label: LY2963016
intervention type: Drug
intervention name: US Approved Lantus
description: Administered subcutaneously
arm group label: US-approved Lantus
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: Insulin Glargine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 