<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/NCT01671085</url>
  </required_header>
  <id_info>
    <org_study_id>14938</org_study_id>
    <secondary_id>I5S-EW-EFJD</secondary_id>
    <nct_id>NCT01671085</nct_id>
  </id_info>
  <brief_title>A Study of LY3015014 in Healthy Participants With High Cholesterol</brief_title>
  <official_title>A Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3015014 in Subjects With Elevated LDL-C on a Stable Statin Therapy</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 is a study in healthy participants with high levels of &quot;bad&quot; cholesterol who are already&#xD;
      taking a popular type of cholesterol-lowering medication called statins. Following multiple&#xD;
      doses of LY3015014, investigators will study the safety and tolerability of the drug, how the&#xD;
      body handles the drug, and the drug's effect on the body. Participants will remain in the&#xD;
      study for about 3 months, not including screening. Screening is required within 28 days&#xD;
      before the study starts.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">March 2013</completion_date>
  <primary_completion_date type="Actual">March 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>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs)</measure>
    <time_frame>Baseline through study completion (Day 127)</time_frame>
    <description>Events deemed to be SAEs by the Investigator as related to study drug administration were collected during the study and 30 days following study drug administration. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014</measure>
    <time_frame>Day 1 and 29: 4 hours (h) and 24 h postdose</time_frame>
    <description>The Cmax was calculated after each dose of LY3015014.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014</measure>
    <time_frame>Day 1 and 29: 4 h and 24 h postdose</time_frame>
    <description>The AUCt was calculated after each dose of LY3015014.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK: Time of Maximum Concentration (Tmax) of LY3015014</measure>
    <time_frame>Day 1 and 29: 4 h and 24 h postdose</time_frame>
    <description>tmax was calculated after each dosing of LY3015014 and is reported as the number of days for observed maximum concentration of LY3015014.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)</measure>
    <time_frame>Baseline, Day 43 and Day 57</time_frame>
    <description>Percentage change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed model repeated measures (MMRM) analysis adjusted for baseline measurement. Treatment, day after dosing, and treatment-by-day interaction were included in the model.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Healthy Volunteers</condition>
  <condition>Hypercholesterolemia</condition>
  <arm_group>
    <arm_group_label>1.0 milligrams per kilogram (mg/kg) of LY3015014</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1.0 mg/kg of LY3015014 given subcutaneously (SQ) on 2 dosing occasions occurring 4 weeks apart (Q4W) (Days 1 and 29).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0.9% sodium chloride injection given SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY3015014</intervention_name>
    <description>Administered SQ</description>
    <arm_group_label>1.0 milligrams per kilogram (mg/kg) of LY3015014</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administered SQ</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must be healthy males or females without childbearing potential as&#xD;
             determined by medical history and physical examination&#xD;
&#xD;
          -  Have body mass indexes of 18 to 35 kilograms per square meter (kg/m^2), inclusive, at&#xD;
             screening&#xD;
&#xD;
          -  Have screening low density lipoprotein-C (LDL-C) of between 100 and 180 milligrams per&#xD;
             deciliter (mg/dL), inclusive, while having taken a stable dose of statin&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have known allergies to compounds related to LY3015014 or any components of the&#xD;
             formulation or known clinically significant hypersensitivity to biologic agents&#xD;
&#xD;
          -  Have a history of atopy, significant allergies to humanized monoclonal antibodies,&#xD;
             clinically significant multiple or severe drug allergies, intolerance to topical&#xD;
             corticosteroids, or severe post treatment hypersensitivity reactions [including but&#xD;
             not limited to erythema multiforme major, linear immunoglobulin A (IgA) dermatosis,&#xD;
             toxic epidermal necrolysis, or exfoliative dermatitis]&#xD;
&#xD;
          -  Have significant history of or current cardiovascular (excluding controlled&#xD;
             hypertension), respiratory, hepatic, renal, gastrointestinal, endocrine,&#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;
          -  Have received any vaccine(s) within 1 month of LY3015014 dosing or intend to do so&#xD;
             during the study&#xD;
&#xD;
          -  Have received treatment with biologic agents (such as monoclonal antibodies) within 3&#xD;
             months or 5 half-lives (whichever is longer) prior to dosing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 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>Miramar</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>August 20, 2012</study_first_submitted>
  <study_first_submitted_qc>August 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 23, 2012</study_first_posted>
  <results_first_submitted>October 17, 2018</results_first_submitted>
  <results_first_submitted_qc>October 17, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">February 25, 2019</results_first_posted>
  <last_update_submitted>February 22, 2019</last_update_submitted>
  <last_update_submitted_qc>February 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2019</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>Hypercholesterolemia</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Participants who discontinued from the study prior to completion were permitted to be replaced.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>1.0 mg/kg of LY3015014</title>
          <description>LY3015014: 1.0 milligram per kilogram (mg/kg) of LY3015014 subcutaneously (SQ) on 2 dosing occasions occurring 4 weeks apart (Q4W) (Days 1 and 29).</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11">1 participant who dropped out was replaced.</participants>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="2"/>
              </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_list>
    </participant_flow>

    <baseline>
      <population>All randomized participants.</population>
      <group_list>
        <group group_id="B1">
          <title>1.0 mg/kg of LY3015014</title>
          <description>LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions (Q4W) (Days 1 and 29).</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="13"/>
          </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="55.0" spread="6.3"/>
                    <measurement group_id="B2" value="52.0" spread="4.2"/>
                    <measurement group_id="B3" value="54.5" spread="6.0"/>
                  </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="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="10"/>
                  </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="10"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Low Density Lipoprotein (LDL)-C</title>
          <units>milligrams/deciliter (mg/dL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="134.430" spread="24.559"/>
                    <measurement group_id="B2" value="161.060" spread="1.372"/>
                    <measurement group_id="B3" value="138.527" spread="24.552"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs)</title>
        <description>Events deemed to be SAEs by the Investigator as related to study drug administration were collected during the study and 30 days following study drug administration. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.</description>
        <time_frame>Baseline through study completion (Day 127)</time_frame>
        <population>All enrolled participants.</population>
        <group_list>
          <group group_id="O1">
            <title>1.0 mg/kg of LY3015014</title>
            <description>LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs)</title>
          <description>Events deemed to be SAEs by the Investigator as related to study drug administration were collected during the study and 30 days following study drug administration. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.</description>
          <population>All enrolled participants.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014</title>
        <description>The Cmax was calculated after each dose of LY3015014.</description>
        <time_frame>Day 1 and 29: 4 hours (h) and 24 h postdose</time_frame>
        <population>Full analysis set (FAS): Data from all randomized participants who received at least 1 dose of the study drug according to the treatment the participants actually received and had evaluable PK data for Cmax.</population>
        <group_list>
          <group group_id="O1">
            <title>1.0 mg/kg of LY3015014</title>
            <description>LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014</title>
          <description>The Cmax was calculated after each dose of LY3015014.</description>
          <population>Full analysis set (FAS): Data from all randomized participants who received at least 1 dose of the study drug according to the treatment the participants actually received and had evaluable PK data for Cmax.</population>
          <units>micrograms per milliliter (µg/mL)</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="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After Day 1 dosing</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.06" spread="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Day 29 dosing</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.57" spread="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014</title>
        <description>The AUCt was calculated after each dose of LY3015014.</description>
        <time_frame>Day 1 and 29: 4 h and 24 h postdose</time_frame>
        <population>FAS: Data from all randomized participants who received at least 1 dose of study drug according to the treatment the participants actually received and had evaluable PK data for AUCt.</population>
        <group_list>
          <group group_id="O1">
            <title>1.0 mg/kg of LY3015014</title>
            <description>LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).</description>
          </group>
        </group_list>
        <measure>
          <title>PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014</title>
          <description>The AUCt was calculated after each dose of LY3015014.</description>
          <population>FAS: Data from all randomized participants who received at least 1 dose of study drug according to the treatment the participants actually received and had evaluable PK data for AUCt.</population>
          <units>microgram*hour per milliliter (µg*h/mL)</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="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After Day 1 dosing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1960" spread="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Day 29 dosing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2150" spread="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK: Time of Maximum Concentration (Tmax) of LY3015014</title>
        <description>tmax was calculated after each dosing of LY3015014 and is reported as the number of days for observed maximum concentration of LY3015014.</description>
        <time_frame>Day 1 and 29: 4 h and 24 h postdose</time_frame>
        <population>FAS: Data from all randomized participants who received at least 1 dose of study drug according to the treatment the participants actually received and had evaluable PK data for tmax.</population>
        <group_list>
          <group group_id="O1">
            <title>1.0 mg/kg of LY3015014</title>
            <description>LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).</description>
          </group>
        </group_list>
        <measure>
          <title>PK: Time of Maximum Concentration (Tmax) of LY3015014</title>
          <description>tmax was calculated after each dosing of LY3015014 and is reported as the number of days for observed maximum concentration of LY3015014.</description>
          <population>FAS: Data from all randomized participants who received at least 1 dose of study drug according to the treatment the participants actually received and had evaluable PK data for tmax.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After Day 1 dosing</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="4" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Day 29 dosing</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)</title>
        <description>Percentage change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed model repeated measures (MMRM) analysis adjusted for baseline measurement. Treatment, day after dosing, and treatment-by-day interaction were included in the model.</description>
        <time_frame>Baseline, Day 43 and Day 57</time_frame>
        <population>Pharmacodynamic analyses set: Participants who received at least 1 dose of investigational product according to the treatment actually received and had a baseline measurement and at least 1 post baseline measurement for LDL-C.</population>
        <group_list>
          <group group_id="O1">
            <title>1.0 mg/kg of LY3015014</title>
            <description>LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo: 0.9% sodium chloride injection given SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)</title>
          <description>Percentage change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed model repeated measures (MMRM) analysis adjusted for baseline measurement. Treatment, day after dosing, and treatment-by-day interaction were included in the model.</description>
          <population>Pharmacodynamic analyses set: Participants who received at least 1 dose of investigational product according to the treatment actually received and had a baseline measurement and at least 1 post baseline measurement for LDL-C.</population>
          <units>µg/mL</units>
          <param>Least Squares Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 43</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-49.10" lower_limit="-57.34" upper_limit="-40.87"/>
                    <measurement group_id="O2" value="1.38" lower_limit="-17.51" upper_limit="20.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-37.53" lower_limit="-45.79" upper_limit="-29.27"/>
                    <measurement group_id="O2" value="7.58" lower_limit="-11.31" upper_limit="26.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>P-value is for Day 43.</p_value_desc>
            <method>Mixed Effects Model Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-50.49</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-71.27</ci_lower_limit>
            <ci_upper_limit>-29.70</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>P-value is for Day 57.</p_value_desc>
            <method>Mixed Effects Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-45.11</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-65.91</ci_lower_limit>
            <ci_upper_limit>-24.31</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline through Study Completion (Day 127)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>1.0 mg/kg of LY3015014</title>
          <description>LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).</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="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="3" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Faeces discoloured</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Injection site inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Fungal skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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/NCT01671085
org study id: 14938
secondary id: I5S-EW-EFJD
nct id: NCT01671085
lead sponsor: 
has dmc: No
This is a study in healthy participants with high levels of "bad" cholesterol who are already
      taking a popular type of cholesterol-lowering medication called statins. Following multiple
      doses of LY3015014, investigators will study the safety and tolerability of the drug, how the
      body handles the drug, and the drug's effect on the body. Participants will remain in the
      study for about 3 months, not including screening. Screening is required within 28 days
      before the study starts.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs)
time frame: Baseline through study completion (Day 127)
description: Events deemed to be SAEs by the Investigator as related to study drug administration were collected during the study and 30 days following study drug administration. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014
time frame: Day 1 and 29: 4 hours (h) and 24 h postdose
description: The Cmax was calculated after each dose of LY3015014.
measure: PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014
time frame: Day 1 and 29: 4 h and 24 h postdose
description: The AUCt was calculated after each dose of LY3015014.
measure: PK: Time of Maximum Concentration (Tmax) of LY3015014
time frame: Day 1 and 29: 4 h and 24 h postdose
description: tmax was calculated after each dosing of LY3015014 and is reported as the number of days for observed maximum concentration of LY3015014.
measure: Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
time frame: Baseline, Day 43 and Day 57
description: Percentage change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed model repeated measures (MMRM) analysis adjusted for baseline measurement. Treatment, day after dosing, and treatment-by-day interaction were included in the model.
arm group label: 1.0 milligrams per kilogram (mg/kg) of LY3015014
arm group type: Experimental
description: 1.0 mg/kg of LY3015014 given subcutaneously (SQ) on 2 dosing occasions occurring 4 weeks apart (Q4W) (Days 1 and 29).
arm group label: Placebo
arm group type: Placebo Comparator
description: 0.9% sodium chloride injection given SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).
intervention type: Drug
intervention name: LY3015014
description: Administered SQ
arm group label: 1.0 milligrams per kilogram (mg/kg) of LY3015014
intervention type: Drug
intervention name: Placebo
description: Administered SQ
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 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: United States
responsible party type: Sponsor
mesh term: Hypercholesterolemia
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 