<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/NCT02197520</url>
  </required_header>
  <id_info>
    <org_study_id>15407</org_study_id>
    <secondary_id>I2R-MC-BIDV</secondary_id>
    <nct_id>NCT02197520</nct_id>
  </id_info>
  <brief_title>A Study To Compare the Effects of Insulin Peglispro and Glargine on Insulin Sensitivity and Meal Time Insulin Requirements in Type 2 Diabetics</brief_title>
  <official_title>The Effect of Treatment With Basal Insulin Peglispro or Insulin Glargine on Insulin Sensitivity and the Effect of Prandial Insulin Lispro in Patients With Type 2 Diabetes Mellitus</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>
      This study will look into insulin sensitivity (how the body responds to insulin) and effects&#xD;
      of meals on type 2 diabetics comparing insulin peglispro to insulin glargine. The study has&#xD;
      two treatment periods, each of which will last about four weeks. One drug (insulin peglispro&#xD;
      or insulin glargine) will be administered in each period. Participants will receive both&#xD;
      drugs during the study. Participants may remain on stable dose metformin, as prescribed by&#xD;
      their personal physician.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</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>Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)</measure>
    <time_frame>Day 33, last 30 minutes (final step) of euglycemic 2-step hyperinsulinemic clamp</time_frame>
    <description>During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro</measure>
    <time_frame>Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Curve Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro</measure>
    <time_frame>Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Acetaminophen</measure>
    <time_frame>Day 29:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29</measure>
    <time_frame>Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfast</time_frame>
    <description>VAS was scored from 0 - 100 millimeters (mm) as a perception of appetite and satiety (Flint et al. 2000), 0 being not hungry at all or nothing at all and 100 being extremely hungry and extremely large amount.&#xD;
The questions are abbreviated in table from: How hungry do you feel right now? to Hunger and How much food do you think you could eat right now? to Food amount. Scores were averaged and will be presented and calculated by a sum of the scores dividing by the total by the number of scores reported for timepoints.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp</measure>
    <time_frame>Day 33 during euglycemic 2-step hyperinsulinemic clamp</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Insulin Peglispro (with Insulin Lispro)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Insulin peglispro, a once daily subcutaneous(SC) injection at bedtime for 5 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Insulin Glargine (with Insulin Lispro)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Insulin glargine, a once daily subcutaneous(SC) injection at bedtime for 5 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin Peglispro</intervention_name>
    <description>Administered subcutaneously (SC), (U-100 formulation)</description>
    <arm_group_label>Insulin Peglispro (with Insulin Lispro)</arm_group_label>
    <other_name>LY2605541</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin Glargine</intervention_name>
    <description>Administered subcutaneously (SC), (U-100 formulation)</description>
    <arm_group_label>Insulin Glargine (with Insulin Lispro)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin Lispro</intervention_name>
    <description>Administered subcutaneously (SC), (U-100 formulation)</description>
    <arm_group_label>Insulin Glargine (with Insulin Lispro)</arm_group_label>
    <arm_group_label>Insulin Peglispro (with Insulin Lispro)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Stable glycated hemoglobin (HbA1c) less than (&lt;) 10.0 percent (%)&#xD;
&#xD;
          -  Stable dose of either 0.2 to 1.5 units per kilogram per day (U/kg/day) basal insulin&#xD;
             or a total daily insulin dose l&lt;2.0 units per kilogram (U/kg)&#xD;
&#xD;
          -  C-peptide &lt;0.3 nanomole per liter (nmol/L)&#xD;
&#xD;
          -  Stable body during the last 2 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Corrected QT interval (QTc) prolongation greater than (&gt;) 500 milliseconds (ms) or&#xD;
             have any other abnormality in the 12 lead&#xD;
&#xD;
          -  Abnormal blood pressure&#xD;
&#xD;
          -  A history or presence of cardiovascular, respiratory, hepatic, renal,&#xD;
             gastrointestinal, endocrine (apart from Type 1 Diabetes Mellitus (T1DM)),&#xD;
             hematological, or neurological disorders capable of significantly altering the&#xD;
             absorption, metabolism, or elimination of drugs; of constituting a risk when taking&#xD;
             the study medication; or of interfering with the interpretation of data&#xD;
&#xD;
          -  Currently treated with oral antidiabetic drugs (OADs) (excluding metformin and&#xD;
             dipeptidyl peptidase-4 (DPP4) inhibitors), or glucagon-like peptide-1 (GLP-1) agonists&#xD;
             or intend to use over-the counter or prescription medication, herbal medications, or&#xD;
             nutritional supplements that affect PG or insulin sensitivity, impact on hypoglycemic&#xD;
             awareness or promote weight loss within 4 weeks prior to randomization&#xD;
&#xD;
          -  Fasting triglycerides (TGs) &gt;400 milligrams per deciliter (mg/dL) (4.52 millimoles per&#xD;
             liter (mmol/L))&#xD;
&#xD;
          -  Have used systemic or inhaled corticosteroids/glucocorticoid therapy (excluding&#xD;
             topical, intra-articular, and intraocular preparations) within 4 weeks prior to&#xD;
             randomization&#xD;
&#xD;
          -  Currently receive insulin by pump or insulin degludec&#xD;
&#xD;
          -  Poorly controlled diabetes or known to have poor awareness of hypoglycemia&#xD;
&#xD;
          -  History of gastroparesis or gastrointestinal malabsorption&#xD;
&#xD;
          -  Require treatment with any drug other than insulin to treat diabetes&#xD;
&#xD;
          -  Previous history of proliferative retinopathy&#xD;
&#xD;
          -  Excessive consumers of xanthines&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)</last_name>
    <role>Study Director</role>
    <affiliation>Eli Lilly and Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Profil Institute for Clinical Research Inc</name>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <zip>91911</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <results_first_submitted>March 17, 2018</results_first_submitted>
  <results_first_submitted_qc>October 29, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">November 1, 2018</results_first_posted>
  <last_update_submitted>October 29, 2018</last_update_submitted>
  <last_update_submitted_qc>October 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2018</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</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
    <mesh_term>Insulin Glargine</mesh_term>
    <mesh_term>Insulin Lispro</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sequence AB</title>
          <description>A: Insulin peglispro, administered SC for 33 days B. Insulin glargine, administered SC for 33 days</description>
        </group>
        <group group_id="P2">
          <title>Sequence BA</title>
          <description>B. Insulin glargine, administered SC for 33 days A: Insulin peglispro, administered SC for 33 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="12"/>
              </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 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </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>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </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_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>All participants who received Insulin peglispro, administered SC for 33 days then Insulin glargine, administered SC for 33 days or Insulin glargine, administered SC for 33 days then Insulin peglispro, administered SC for 33 days</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="24"/>
          </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="51.3" spread="9.1"/>
                  </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="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</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="24"/>
                  </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="1"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)</title>
        <description>During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure.</description>
        <time_frame>Day 33, last 30 minutes (final step) of euglycemic 2-step hyperinsulinemic clamp</time_frame>
        <population>All participants who received at least 1 dose of study drug and had evaluable PD parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin Peglispro</title>
            <description>Insulin peglispro, a once daily SC</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Insulin glargine, a once daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)</title>
          <description>During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure.</description>
          <population>All participants who received at least 1 dose of study drug and had evaluable PD parameters.</population>
          <units>milligram*hour per deciliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>High Dose Insulin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.09" spread="10.48"/>
                    <measurement group_id="O2" value="55.52" spread="16.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Low Dose Insulin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.22" spread="6.24"/>
                    <measurement group_id="O2" value="19.67" spread="7.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro</title>
        <time_frame>Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast</time_frame>
        <population>All participants who received at least 1 dose of study drug and had evaluable PD parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin Peglispro</title>
            <description>Insulin peglispro, once daily SC</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Insulin glargine, a once daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro</title>
          <population>All participants who received at least 1 dose of study drug and had evaluable PD parameters.</population>
          <units>milligram*hour per deciliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>10% Insulin Lispro Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="437.78" spread="147.47"/>
                    <measurement group_id="O2" value="398.26" spread="159.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20% Insulin Lispro Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="334.23" spread="165.96"/>
                    <measurement group_id="O2" value="343.54" spread="182.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30% Insulin Lispro Dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="244.68" spread="136.01"/>
                    <measurement group_id="O2" value="239.83" spread="175.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Area Under the Concentration Curve Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro</title>
        <time_frame>Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast</time_frame>
        <population>All participants who received at least 1 dose of study drug and had evaluable PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin Peglispro</title>
            <description>Insulin peglispro, a once daily SC</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Insulin glargine, a once daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Concentration Curve Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro</title>
          <population>All participants who received at least 1 dose of study drug and had evaluable PK parameters.</population>
          <units>picomol*hour per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="839" spread="47"/>
                    <measurement group_id="O2" value="835" spread="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Acetaminophen</title>
        <time_frame>Day 29:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast</time_frame>
        <population>All participants who received at least 1 dose of study drug and had evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin Peglispro</title>
            <description>Insulin peglispro, a once daily SC</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Insulin glargine, a once daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Acetaminophen</title>
          <population>All participants who received at least 1 dose of study drug and had evaluable PK data.</population>
          <units>nanograms*hour per milliliter</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="23"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33700" spread="28"/>
                    <measurement group_id="O2" value="35700" spread="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29</title>
        <description>VAS was scored from 0 - 100 millimeters (mm) as a perception of appetite and satiety (Flint et al. 2000), 0 being not hungry at all or nothing at all and 100 being extremely hungry and extremely large amount.&#xD;
The questions are abbreviated in table from: How hungry do you feel right now? to Hunger and How much food do you think you could eat right now? to Food amount. Scores were averaged and will be presented and calculated by a sum of the scores dividing by the total by the number of scores reported for timepoints.</description>
        <time_frame>Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfast</time_frame>
        <population>All participants who received at least 1 dose of study drug and had a VAS score.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin Peglispro</title>
            <description>Insulin peglispro, a once daily SC</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Insulin glargine, a once daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29</title>
          <description>VAS was scored from 0 - 100 millimeters (mm) as a perception of appetite and satiety (Flint et al. 2000), 0 being not hungry at all or nothing at all and 100 being extremely hungry and extremely large amount.&#xD;
The questions are abbreviated in table from: How hungry do you feel right now? to Hunger and How much food do you think you could eat right now? to Food amount. Scores were averaged and will be presented and calculated by a sum of the scores dividing by the total by the number of scores reported for timepoints.</description>
          <population>All participants who received at least 1 dose of study drug and had a VAS score.</population>
          <units>millimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hunger: Waking</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.7" spread="23.2"/>
                    <measurement group_id="O2" value="38.6" spread="31.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Food amount: Waking</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.2" spread="23.9"/>
                    <measurement group_id="O2" value="34.4" spread="25.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hunger: Pre-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.5" spread="30.1"/>
                    <measurement group_id="O2" value="51.4" spread="32.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Food amount: Pre-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.9" spread="27.7"/>
                    <measurement group_id="O2" value="51.5" spread="30.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hunger: 1 hour Post-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8" spread="12.8"/>
                    <measurement group_id="O2" value="6.2" spread="16.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Food amount: 1 hour Post-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.7" spread="12.2"/>
                    <measurement group_id="O2" value="6.0" spread="11.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hunger: 2 hour Post-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.7" spread="23.5"/>
                    <measurement group_id="O2" value="14.9" spread="19.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Food amount: 2 hour Post-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.7" spread="24.2"/>
                    <measurement group_id="O2" value="16.3" spread="17.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hunger:3 hour Post-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.8" spread="26.5"/>
                    <measurement group_id="O2" value="29.2" spread="20.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Food amount: 3 hour Post-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.6" spread="27.3"/>
                    <measurement group_id="O2" value="31.1" spread="20.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hunger: 4 hour Post-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.6" spread="27.8"/>
                    <measurement group_id="O2" value="48.0" spread="28.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Food amount: 4 hour Post-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.2" spread="27.5"/>
                    <measurement group_id="O2" value="48.5" spread="28.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hunger: 5 hour Post-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.8" spread="28.6"/>
                    <measurement group_id="O2" value="55.5" spread="34.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Food amount: 5 hour Post-breakfast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.5" spread="27.2"/>
                    <measurement group_id="O2" value="53.4" spread="34.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp</title>
        <time_frame>Day 33 during euglycemic 2-step hyperinsulinemic clamp</time_frame>
        <population>No participant analyzed because Outcome Measure was incorrectly registered.</population>
        <group_list>
          <group group_id="O1">
            <title>Insulin Peglispro</title>
            <description>Insulin peglispro, a once daily SC</description>
          </group>
          <group group_id="O2">
            <title>Insulin Glargine</title>
            <description>Insulin peglispro, a once daily SC</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp</title>
          <population>No participant analyzed because Outcome Measure was incorrectly registered.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Insulin Peglispro</title>
          <description>Insulin peglispro, a once daily SC</description>
        </group>
        <group group_id="E2">
          <title>Insulin Glargine</title>
          <description>Insulin glargine, a once daily SC</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="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.0</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="14" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Catheter site related reaction</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Injection site haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Vessel puncture site bruise</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Medical Officer</name_or_title>
      <organization>Eli Lilly and Company</organization>
      <phone>800-545-5979</phone>
    </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/NCT02197520
org study id: 15407
secondary id: I2R-MC-BIDV
nct id: NCT02197520
lead sponsor: 
has dmc: No
This study will look into insulin sensitivity (how the body responds to insulin) and effects
      of meals on type 2 diabetics comparing insulin peglispro to insulin glargine. The study has
      two treatment periods, each of which will last about four weeks. One drug (insulin peglispro
      or insulin glargine) will be administered in each period. Participants will receive both
      drugs during the study. Participants may remain on stable dose metformin, as prescribed by
      their personal physician.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)
time frame: Day 33, last 30 minutes (final step) of euglycemic 2-step hyperinsulinemic clamp
description: During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure.
measure: Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro
time frame: Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast
measure: Pharmacokinetics (PK): Area Under the Concentration Curve Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro
time frame: Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast
measure: Pharmacokinetics (PK): Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Acetaminophen
time frame: Day 29:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast
measure: Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
time frame: Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfast
description: VAS was scored from 0 - 100 millimeters (mm) as a perception of appetite and satiety (Flint et al. 2000), 0 being not hungry at all or nothing at all and 100 being extremely hungry and extremely large amount.
The questions are abbreviated in table from: How hungry do you feel right now? to Hunger and How much food do you think you could eat right now? to Food amount. Scores were averaged and will be presented and calculated by a sum of the scores dividing by the total by the number of scores reported for timepoints.
measure: Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp
time frame: Day 33 during euglycemic 2-step hyperinsulinemic clamp
arm group label: Insulin Peglispro (with Insulin Lispro)
arm group type: Experimental
description: Insulin peglispro, a once daily subcutaneous(SC) injection at bedtime for 5 weeks
arm group label: Insulin Glargine (with Insulin Lispro)
arm group type: Active Comparator
description: Insulin glargine, a once daily subcutaneous(SC) injection at bedtime for 5 weeks
intervention type: Drug
intervention name: Insulin Peglispro
description: Administered subcutaneously (SC), (U-100 formulation)
arm group label: Insulin Peglispro (with Insulin Lispro)
other name: LY2605541
intervention type: Drug
intervention name: Insulin Glargine
description: Administered subcutaneously (SC), (U-100 formulation)
arm group label: Insulin Glargine (with Insulin Lispro)
intervention type: Drug
intervention name: Insulin Lispro
description: Administered subcutaneously (SC), (U-100 formulation)
arm group label: Insulin Glargine (with Insulin Lispro)
arm group label: Insulin Peglispro (with Insulin Lispro)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: Study Director
affiliation: Eli Lilly and Company
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin Resistance
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Insulin Glargine
mesh term: Insulin Lispro
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 