<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/NCT01709513</url>
  </required_header>
  <id_info>
    <org_study_id>R727-CL-1119</org_study_id>
    <nct_id>NCT01709513</nct_id>
  </id_info>
  <brief_title>Study of Alirocumab (REGN727/SAR236553) in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular (CV) Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE)</brief_title>
  <official_title>A Randomized, Double-Blind, Double-Dummy, Active-Controlled Study to Evaluate the Efficacy and Safety of REGN727/SAR236553 in Patients With Primary Hypercholesterolemia Who Are Intolerant to Statins</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Regeneron Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, double-blind, double-dummy, active-controlled, parallel-group,&#xD;
      multi-national, multi-center study to compare alirocumab (REGN727/SAR236553) versus ezetimibe&#xD;
      in participants with primary hypercholesterolemia and moderate, high, or very high CV risk,&#xD;
      who are intolerant to statins. An atorvastatin arm is added to determine that the population&#xD;
      selected in the study is a truly statin intolerant population by assessing skeletal&#xD;
      muscle-related adverse events.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 30, 2012</start_date>
  <completion_date type="Actual">May 31, 2017</completion_date>
  <primary_completion_date type="Actual">May 31, 2014</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent--To-Treat (ITT) Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Calculated LDL-C at Week 24 - On--Treatment Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Calculated LDL--C at Week 12 -- ITT Analysis</measure>
    <time_frame>From Baseline to Week 12</time_frame>
    <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis</measure>
    <time_frame>From Baseline to Week 12</time_frame>
    <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 -- ITT Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post--baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Apo B at Week 24 -- On--Treatment Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Non--High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 -- ITT Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Non--HDL-C at Week 24 -- On--Treatment Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Total Cholesterol (Total--C) at Week 24 - ITT Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Apo B at Week 12 -- ITT Analysis</measure>
    <time_frame>From Baseline to Week 12</time_frame>
    <description>Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis</measure>
    <time_frame>From Baseline to Week 12</time_frame>
    <description>Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Total-C at Week 12 - ITT Analysis</measure>
    <time_frame>From Baseline to Week 12</time_frame>
    <description>Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Very High CV Risk Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C &lt;100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis</measure>
    <time_frame>Up to Week 24</time_frame>
    <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Very High CV Risk Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C &lt;100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis</measure>
    <time_frame>Up to Week 24</time_frame>
    <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis</measure>
    <time_frame>Up to Week 24</time_frame>
    <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis</measure>
    <time_frame>Up to Week 24</time_frame>
    <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis</measure>
    <time_frame>From Baseline to Week 24</time_frame>
    <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Lipoprotein(a) at Week 12 -- ITT Analysis</measure>
    <time_frame>From Baseline to Week 12</time_frame>
    <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis</measure>
    <time_frame>From Baseline to Week 12</time_frame>
    <description>Least-squares (LS) means and standard errors (SE) taken from MMRM (mixed-effect model with repeated measures) analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis</measure>
    <time_frame>From Baseline to Week 12</time_frame>
    <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis</measure>
    <time_frame>From Baseline to Week 12</time_frame>
    <description>Least squares (LS) means and standard errors (SE) taken from MMRM (mixed effect model with repeated measures) analysis.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE)</measure>
    <time_frame>From Baseline up to Week 24</time_frame>
    <description>Skeletal muscle-related adverse events were a predefined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness and muscle fatigue. Events that developed during treatment emergent adverse events period (the time from the first double-blindstudy treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.</description>
  </other_outcome>
  <other_outcome>
    <measure>Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis</measure>
    <time_frame>From Baseline up to Week 24</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">314</enrollment>
  <condition>Hypercholesterolemia</condition>
  <arm_group>
    <arm_group_label>Atorvastatin (statin rechallenge arm)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable lipid-modifying therapy (LMT).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ezetimibe</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alirocumab 75 mg/ up to 150 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin</intervention_name>
    <description>Atorvastatin over-encapsulated tablets.</description>
    <arm_group_label>Atorvastatin (statin rechallenge arm)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ezetimibe</intervention_name>
    <description>Ezetimibe over-encapsulated tablet.</description>
    <arm_group_label>Ezetimibe</arm_group_label>
    <other_name>Zetia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alirocumab</intervention_name>
    <description>Alirocumab SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.</description>
    <arm_group_label>Alirocumab 75 mg/ up to 150 mg</arm_group_label>
    <other_name>REGN727/SAR236553</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo for alirocumab, ezitimibe and atorvastatin.</description>
    <arm_group_label>Alirocumab 75 mg/ up to 150 mg</arm_group_label>
    <arm_group_label>Atorvastatin (statin rechallenge arm)</arm_group_label>
    <arm_group_label>Ezetimibe</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion:&#xD;
&#xD;
          1. Patients with primary hypercholesterolemia [Heterozygous Familial Hypercholesterolemia&#xD;
             (heFH) or non-FH] with moderate, high or very high CV risk and a history of statin&#xD;
             intolerance&#xD;
&#xD;
          2. Provide signed informed consent&#xD;
&#xD;
        Exclusion:&#xD;
&#xD;
          1. Calculated serum LDL-C &lt;70 mg/dL (1.81 mmol/L) and very high CV risk at the screening&#xD;
             visit&#xD;
&#xD;
          2. Calculated serum LDL-C &lt;100 mg/dL (2.59 mmol/L) and high or moderate CV risk at the&#xD;
             screening visit&#xD;
&#xD;
          3. A 10-year fatal cardiovascular disease risk score &lt;1% at the screening visit&#xD;
&#xD;
        (The inclusion/ exclusion criteria provided above is not intended to contain all&#xD;
        considerations relevant to a patient's potential participation in this clinical trial).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trial Management</last_name>
    <role>Study Director</role>
    <affiliation>Regeneron Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Mission Viejo</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Northridge</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Thousand Oaks</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boynton Beach</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lakeland</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Trinity</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Addison</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Auburn</city>
        <state>Maine</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Clifton</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Poughkeepsie</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Marion</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Port Matilda</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Scranton</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wilkes-Barre</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Summerville</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kingsport</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Feldkirch</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Graz</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Innsbruck</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicoutimi</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Montreal (2 locations)</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sainte-Foy</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bron</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint-Herblain</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Venissieux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Holon</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ofakim</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Safed</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tel-Hashomer</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cinisello Balsamo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Palermo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oslo (2 Locations)</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Burton-on-Trent</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chesterfield</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Isle Of White</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Londonderry/N. Ireland</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Peterborough</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Salford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Stevenage</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Canada</country>
    <country>France</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Norway</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
    <country>Netherlands</country>
  </removed_countries>
  <reference>
    <citation>Moriarty PM, Jacobson TA, Bruckert E, Thompson PD, Guyton JR, Baccara-Dinet MT, Gipe D. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol. 2014 Nov-Dec;8(6):554-561. doi: 10.1016/j.jacl.2014.09.007. Epub 2014 Sep 19.</citation>
    <PMID>25499937</PMID>
  </reference>
  <results_reference>
    <citation>Moriarty PM, Thompson PD, Cannon CP, Guyton JR, Bergeron J, Zieve FJ, Bruckert E, Jacobson TA, Kopecky SL, Baccara-Dinet MT, Du Y, Pordy R, Gipe DA; ODYSSEY ALTERNATIVE Investigators. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol. 2015 Nov-Dec;9(6):758-769. doi: 10.1016/j.jacl.2015.08.006. Epub 2015 Aug 29.</citation>
    <PMID>26687696</PMID>
  </results_reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>July 29, 2015</results_first_submitted>
  <results_first_submitted_qc>July 29, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 28, 2015</results_first_posted>
  <disposition_first_submitted>January 24, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>January 24, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">February 2, 2015</disposition_first_posted>
  <last_update_submitted>June 10, 2020</last_update_submitted>
  <last_update_submitted_qc>June 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypercholesterolemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atorvastatin</mesh_term>
    <mesh_term>Ezetimibe</mesh_term>
    <mesh_term>Alirocumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 67 sites in 8 countries. Overall, 519 participants were screened between 28 September 2012 and 11 August 2013, 158 of whom were screen failures. Screen failures were mainly due to exclusion criteria met. After screening, 361 participants entered into a 4-week single blind placebo run-in period.</recruitment_details>
      <pre_assignment_details>At the end of the single blind placebo run-in period, eligible participants were randomized to treatment arms centrally using a 2:2:1 (alirocumab:ezetimibe:atorvastatin) ratio. Randomization was stratified according to prior history of myocardial infarction or ischemic stroke. 314 participants were randomized.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Atorvastatin (Statin Rechallenge Arm)</title>
          <description>Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable LMT.</description>
        </group>
        <group group_id="P2">
          <title>Ezetimibe (Active Comparator)</title>
          <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
        </group>
        <group group_id="P3">
          <title>Alirocumab 75 mg/ up to 150 mg</title>
          <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="63"/>
                <participants group_id="P2" count="125"/>
                <participants group_id="P3" count="126"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="63"/>
                <participants group_id="P2" count="124"/>
                <participants group_id="P3" count="126"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
                <participants group_id="P2" count="82"/>
                <participants group_id="P3" count="96"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="43"/>
                <participants group_id="P3" count="30"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Randomized but not treated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="31"/>
                <participants group_id="P3" count="23"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Poor compliance to protocol</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Atorvastatin (Statin Rechallenge Arm)</title>
          <description>Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable lipid-modifying therapy (LMT).</description>
        </group>
        <group group_id="B2">
          <title>Ezetimibe (Active Comparator)</title>
          <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
        </group>
        <group group_id="B3">
          <title>Alirocumab 75 mg/ up to 150 mg</title>
          <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
        </group>
        <group group_id="B4">
          <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="63"/>
            <count group_id="B2" value="125"/>
            <count group_id="B3" value="126"/>
            <count group_id="B4" value="314"/>
          </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="63.4" spread="9.5"/>
                    <measurement group_id="B2" value="62.8" spread="10.1"/>
                    <measurement group_id="B3" value="64.1" spread="9.0"/>
                    <measurement group_id="B4" value="63.4" spread="9.5"/>
                  </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="28"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="56"/>
                    <measurement group_id="B4" value="142"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="70"/>
                    <measurement group_id="B4" value="172"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Low Density Lipoprotein Cholesterol (LDL-C) in mg/dL</title>
          <description>Calculated LDL-C values were obtained from Friedewald formula.</description>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="187.3" spread="59.5"/>
                    <measurement group_id="B2" value="193.5" spread="70.9"/>
                    <measurement group_id="B3" value="191.1" spread="72.7"/>
                    <measurement group_id="B4" value="191.3" spread="69.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>LDL-C in mmol/L</title>
          <description>Calculated LDL-C values were obtained from Friedewald formula.</description>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.85" spread="1.54"/>
                    <measurement group_id="B2" value="5.011" spread="1.837"/>
                    <measurement group_id="B3" value="4.951" spread="1.883"/>
                    <measurement group_id="B4" value="4.954" spread="1.796"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent--To-Treat (ITT) Analysis</title>
        <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>ITT population: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent--To-Treat (ITT) Analysis</title>
          <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).</description>
          <population>ITT population: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.6" spread="2.2"/>
                    <measurement group_id="O2" value="-45.0" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Alirocumab group was compared to the corresponding active control group using an appropriate contrast statement.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-30.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-36.6</ci_lower_limit>
            <ci_upper_limit>-24.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Calculated LDL-C at Week 24 - On--Treatment Analysis</title>
        <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>Modified ITT (mITT) population: all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Calculated LDL-C at Week 24 - On--Treatment Analysis</title>
          <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).</description>
          <population>Modified ITT (mITT) population: all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="118"/>
                <count group_id="O2" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.1" spread="2.0"/>
                    <measurement group_id="O2" value="-52.2" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 5% level.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-35.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-40.7</ci_lower_limit>
            <ci_upper_limit>-29.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Calculated LDL--C at Week 12 -- ITT Analysis</title>
        <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 12</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Calculated LDL--C at Week 12 -- ITT Analysis</title>
          <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
          <population>ITT population.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.6" spread="2.0"/>
                    <measurement group_id="O2" value="-47.0" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-31.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-36.9</ci_lower_limit>
            <ci_upper_limit>-26.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis</title>
        <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).</description>
        <time_frame>From Baseline to Week 12</time_frame>
        <population>mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis</title>
          <description>Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).</description>
          <population>mITT population.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="118"/>
                <count group_id="O2" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-18.0" spread="1.8"/>
                    <measurement group_id="O2" value="-51.2" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-33.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-38.0</ci_lower_limit>
            <ci_upper_limit>-28.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 -- ITT Analysis</title>
        <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post--baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 -- ITT Analysis</title>
          <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post--baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
          <population>Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="116"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.2" spread="1.7"/>
                    <measurement group_id="O2" value="-36.3" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-25.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-29.8</ci_lower_limit>
            <ci_upper_limit>-20.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Apo B at Week 24 -- On--Treatment Analysis</title>
        <description>Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Apo B value on-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Apo B at Week 24 -- On--Treatment Analysis</title>
          <description>Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).</description>
          <population>Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Apo B value on-treatment.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="109"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.4" spread="1.4"/>
                    <measurement group_id="O2" value="-42.6" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-28.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-32.1</ci_lower_limit>
            <ci_upper_limit>-24.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Non--High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 -- ITT Analysis</title>
        <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Non--High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 -- ITT Analysis</title>
          <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
          <population>Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.6" spread="1.7"/>
                    <measurement group_id="O2" value="-40.2" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-25.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-30.4</ci_lower_limit>
            <ci_upper_limit>-20.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Non--HDL-C at Week 24 -- On--Treatment Analysis</title>
        <description>Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C value on-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Non--HDL-C at Week 24 -- On--Treatment Analysis</title>
          <description>Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).</description>
          <population>Participants analyzed: participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C value on-treatment.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="118"/>
                <count group_id="O2" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.1" spread="1.5"/>
                    <measurement group_id="O2" value="-46.9" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-29.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-33.9</ci_lower_limit>
            <ci_upper_limit>-25.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Total Cholesterol (Total--C) at Week 24 - ITT Analysis</title>
        <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline total-C value on- or off-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Total Cholesterol (Total--C) at Week 24 - ITT Analysis</title>
          <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
          <population>Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline total-C value on- or off-treatment.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.9" spread="1.4"/>
                    <measurement group_id="O2" value="-31.8" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-20.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-24.7</ci_lower_limit>
            <ci_upper_limit>-17.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Apo B at Week 12 -- ITT Analysis</title>
        <description>Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 12</time_frame>
        <population>Apo B ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Apo B at Week 12 -- ITT Analysis</title>
          <description>Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
          <population>Apo B ITT population.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="116"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.6" spread="1.5"/>
                    <measurement group_id="O2" value="-36.1" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-24.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-28.7</ci_lower_limit>
            <ci_upper_limit>-20.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis</title>
        <description>Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 12</time_frame>
        <population>Non-HDL-C ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis</title>
          <description>Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
          <population>Non-HDL-C ITT population.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.8" spread="1.5"/>
                    <measurement group_id="O2" value="-41.5" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-25.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-29.9</ci_lower_limit>
            <ci_upper_limit>-21.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Total-C at Week 12 - ITT Analysis</title>
        <description>Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 12</time_frame>
        <population>Total-C ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75/ up to 150</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Total-C at Week 12 - ITT Analysis</title>
          <description>Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
          <population>Total-C ITT population.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.6" spread="1.2"/>
                    <measurement group_id="O2" value="-32.7" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-21.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-24.5</ci_lower_limit>
            <ci_upper_limit>-17.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Very High CV Risk Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C &lt;100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis</title>
        <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).</description>
        <time_frame>Up to Week 24</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Very High CV Risk Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C &lt;100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis</title>
          <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).</description>
          <population>ITT population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.4"/>
                    <measurement group_id="O2" value="41.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>19.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>6.9</ci_lower_limit>
            <ci_upper_limit>55.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Very High CV Risk Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C &lt;100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis</title>
        <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).</description>
        <time_frame>Up to Week 24</time_frame>
        <population>mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Very High CV Risk Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C &lt;100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis</title>
          <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).</description>
          <population>mITT population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="118"/>
                <count group_id="O2" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6"/>
                    <measurement group_id="O2" value="51.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>24.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>8.6</ci_lower_limit>
            <ci_upper_limit>71.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis</title>
        <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).</description>
        <time_frame>Up to Week 24</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis</title>
          <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).</description>
          <population>ITT population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="32.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a last observation carried forward (LOCF) approach followed by Exact conditional logistic regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Regression, Exact Conditional Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>71.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>11.1</ci_lower_limit>
            <ci_upper_limit>3022.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis</title>
        <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).</description>
        <time_frame>Up to Week 24</time_frame>
        <population>mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Reaching Calculated LDL-C &lt;70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis</title>
          <description>Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).</description>
          <population>mITT population.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="118"/>
                <count group_id="O2" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="39.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a LOCF approach followed by Exact conditional logistic regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Regression, Exact Conditional Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>109.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>16.5</ci_lower_limit>
            <ci_upper_limit>4759.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis</title>
        <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>Participants analyzed: participants of the ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis</title>
          <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
          <population>Participants analyzed: participants of the ITT population.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.3" spread="2.5"/>
                    <measurement group_id="O2" value="-25.9" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant). Statistical analysis used a multiple imputation approach followed by a robust regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Regression, Robust</method>
            <param_type>Adjusted Mean Difference</param_type>
            <param_value>-18.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-25.5</ci_lower_limit>
            <ci_upper_limit>-11.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis</title>
        <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis</title>
          <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
          <population>Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" spread="1.7"/>
                    <measurement group_id="O2" value="7.7" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Testing according to the hierarchical testing procedure (previous endpoints were statistically significant).</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>=0.6997</p_value>
            <p_value_desc>Threshold for significance ≤ 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.8</ci_lower_limit>
            <ci_upper_limit>5.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis</title>
        <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>Participants analyzed: participants of the ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis</title>
          <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
          <population>Participants analyzed: participants of the ITT population</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.6" spread="2.8"/>
                    <measurement group_id="O2" value="-9.3" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis</title>
        <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 24</time_frame>
        <population>Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis</title>
          <description>Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.</description>
          <population>Participants analyzed: participants of the ITT population with one baseline and at least one post-baseline Apo A-1 value on- or off-treatment.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="116"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.9" spread="1.2"/>
                    <measurement group_id="O2" value="4.8" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Lipoprotein(a) at Week 12 -- ITT Analysis</title>
        <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
        <time_frame>From Baseline to Week 12</time_frame>
        <population>Lipoprotein(a) ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Lipoprotein(a) at Week 12 -- ITT Analysis</title>
          <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
          <population>Lipoprotein(a) ITT population.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.5" spread="2.3"/>
                    <measurement group_id="O2" value="-21.7" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis</title>
        <description>Least-squares (LS) means and standard errors (SE) taken from MMRM (mixed-effect model with repeated measures) analysis</description>
        <time_frame>From Baseline to Week 12</time_frame>
        <population>HDL-C ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis</title>
          <description>Least-squares (LS) means and standard errors (SE) taken from MMRM (mixed-effect model with repeated measures) analysis</description>
          <population>HDL-C ITT population.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.6" spread="1.2"/>
                    <measurement group_id="O2" value="9.0" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis</title>
        <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
        <time_frame>From Baseline to Week 12</time_frame>
        <population>Fasting Triglycerides ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis</title>
          <description>Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.</description>
          <population>Fasting Triglycerides ITT population.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="122"/>
                <count group_id="O2" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.4" spread="2.6"/>
                    <measurement group_id="O2" value="-8.0" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis</title>
        <description>Least squares (LS) means and standard errors (SE) taken from MMRM (mixed effect model with repeated measures) analysis.</description>
        <time_frame>From Baseline to Week 12</time_frame>
        <population>Apo A-1 ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Ezetimibe</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis</title>
          <description>Least squares (LS) means and standard errors (SE) taken from MMRM (mixed effect model with repeated measures) analysis.</description>
          <population>Apo A-1 ITT population.</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="116"/>
                <count group_id="O2" value="122"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9" spread="1.0"/>
                    <measurement group_id="O2" value="5.5" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE)</title>
        <description>Skeletal muscle-related adverse events were a predefined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness and muscle fatigue. Events that developed during treatment emergent adverse events period (the time from the first double-blindstudy treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.</description>
        <time_frame>From Baseline up to Week 24</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>Atorvastatin (Statin Rechallenge Arm)</title>
            <description>Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Ezetimibe (Active Comparator)</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O3">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE)</title>
          <description>Skeletal muscle-related adverse events were a predefined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness and muscle fatigue. Events that developed during treatment emergent adverse events period (the time from the first double-blindstudy treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.</description>
          <population>Safety population</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="124"/>
                <count group_id="O3" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any skeletal muscle-related AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.0"/>
                    <measurement group_id="O2" value="41.1"/>
                    <measurement group_id="O3" value="32.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leading to treatment discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.2"/>
                    <measurement group_id="O2" value="20.2"/>
                    <measurement group_id="O3" value="15.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis</title>
        <time_frame>From Baseline up to Week 24</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Atorvastatin (Statin Rechallenge Arm)</title>
            <description>Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O2">
            <title>Ezetimibe (Active Comparator)</title>
            <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.</description>
          </group>
          <group group_id="O3">
            <title>Alirocumab 75 mg/ up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis</title>
          <population>ITT population</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="106"/>
                <count group_id="O3" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-31.9" spread="25.1"/>
                    <measurement group_id="O2" value="-15.2" spread="22.4"/>
                    <measurement group_id="O3" value="-47.3" spread="22.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Baseline up to the Last Double-Blind Injection Date + 70 Days</time_frame>
      <desc>Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first double-blind study treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.</desc>
      <group_list>
        <group group_id="E1">
          <title>Atorvastatin</title>
          <description>Atorvastatin 20 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 22 weeks added to stable LMT.</description>
        </group>
        <group group_id="E2">
          <title>Ezetimibe</title>
          <description>Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo for alirocumab SC injection Q2W for 22 weeks added to stable LMT.</description>
        </group>
        <group group_id="E3">
          <title>Alirocumab 75 mg/ up to 150 mg</title>
          <description>Alirocumab 75 mg SC injection Q2W for 22 weeks and placebo for atorvastatin/ezetimibe over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL--C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.</description>
        </group>
      </group_list>
      <serious_events>
        <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, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Aortic valve incompetence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Cardiovascular disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Peritoneal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-Cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Post procedural haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Traumatic arthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Haemarthrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Clear cell renal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Colon cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Malignant melanoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Ovarian epithelial cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Loss of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic aneurysm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="126"/>
              </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="35" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="63" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="57" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="63"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="124"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="31" subjects_at_risk="126"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="126"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="63"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="124"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="126"/>
              </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>Not less than 45 days prior to submission for publication or presentation, the Institution shall, or cause the Principal Investigator to, provide the Sponsor with a copy of the Manuscript. The Institution shall consider in good faith any comments from the Sponsor regarding the content, and shall delete Confidential Information upon written request of the Sponsor. At the Sponsor's request, the Institution shall delay publication for an additional 60 days to allow patent applications to be filed.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trial Administrator</name_or_title>
      <organization>Regeneron Pharmaceuticals, Inc</organization>
      <email>clinicaltrials@regeneron.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01709513
org study id: R727-CL-1119
nct id: NCT01709513
lead sponsor: 
collaborator: 
has dmc: Yes
This is a randomized, double-blind, double-dummy, active-controlled, parallel-group,
      multi-national, multi-center study to compare alirocumab (REGN727/SAR236553) versus ezetimibe
      in participants with primary hypercholesterolemia and moderate, high, or very high CV risk,
      who are intolerant to statins. An atorvastatin arm is added to determine that the population
      selected in the study is a truly statin intolerant population by assessing skeletal
      muscle-related adverse events.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent--To-Treat (ITT) Analysis
time frame: From Baseline to Week 24
description: Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 - On--Treatment Analysis
time frame: From Baseline to Week 24
description: Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).
measure: Percent Change From Baseline in Calculated LDL--C at Week 12 -- ITT Analysis
time frame: From Baseline to Week 12
description: Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - On--Treatment Analysis
time frame: From Baseline to Week 12
description: Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first) (on-treatment analysis).
measure: Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 -- ITT Analysis
time frame: From Baseline to Week 24
description: Adjusted LS means and standard errors at Week 24 from MMRM model including all available post--baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
measure: Percent Change From Baseline in Apo B at Week 24 -- On--Treatment Analysis
time frame: From Baseline to Week 24
description: Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
measure: Percent Change From Baseline in Non--High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 -- ITT Analysis
time frame: From Baseline to Week 24
description: Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
measure: Percent Change From Baseline in Non--HDL-C at Week 24 -- On--Treatment Analysis
time frame: From Baseline to Week 24
description: Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first).
measure: Percent Change From Baseline in Total Cholesterol (Total--C) at Week 24 - ITT Analysis
time frame: From Baseline to Week 24
description: Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
measure: Percent Change From Baseline in Apo B at Week 12 -- ITT Analysis
time frame: From Baseline to Week 12
description: Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
measure: Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
time frame: From Baseline to Week 12
description: Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
measure: Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
time frame: From Baseline to Week 12
description: Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
measure: Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis
time frame: Up to Week 24
description: Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).
measure: Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or Moderate or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis
time frame: Up to Week 24
description: Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).
measure: Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
time frame: Up to Week 24
description: Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).
measure: Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
time frame: Up to Week 24
description: Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule, whichever came first (on-treatment analysis).
measure: Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
time frame: From Baseline to Week 24
description: Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
measure: Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
time frame: From Baseline to Week 24
description: Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
measure: Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
time frame: From Baseline to Week 24
description: Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
measure: Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
time frame: From Baseline to Week 24
description: Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
measure: Percent Change From Baseline in Lipoprotein(a) at Week 12 -- ITT Analysis
time frame: From Baseline to Week 12
description: Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
measure: Percent Change in HDL-C From Baseline to Week 12 -- ITT Analysis
time frame: From Baseline to Week 12
description: Least-squares (LS) means and standard errors (SE) taken from MMRM (mixed-effect model with repeated measures) analysis
measure: Percent Change in Fasting Triglycerides From Baseline to Week 12 -- ITT Analysis
time frame: From Baseline to Week 12
description: Combined Estimate for Adjusted Mean (Standard Error) at Week 24 from multiple imputation followed by robust regression including all available post-baseline data from Week 4 to Week 24 regardless of status on or off-treatment.
measure: Percent Change From Baseline in Apo A--1 at Week 12 -- ITT Analysis
time frame: From Baseline to Week 12
description: Least squares (LS) means and standard errors (SE) taken from MMRM (mixed effect model with repeated measures) analysis.
measure: Percentage of Participants Who Experienced Skeletal Muscle-related Adverse Event (AE)
time frame: From Baseline up to Week 24
description: Skeletal muscle-related adverse events were a predefined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness and muscle fatigue. Events that developed during treatment emergent adverse events period (the time from the first double-blindstudy treatment [injection or capsules, whichever came first] up to the day of the last double-blind injection + 70 days ) are reported.
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 Versus Atorvastatin - Raw Data Description - Intent-To-Treat (ITT) Analysis
time frame: From Baseline up to Week 24
arm group label: Atorvastatin (statin rechallenge arm)
arm group type: Other
description: Atorvastatin 20 mg over-encapsulated tablets orally once daily (QD) for 24 weeks and placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) for 24 weeks added to stable lipid-modifying therapy (LMT).
arm group label: Ezetimibe
arm group type: Active Comparator
description: Ezetimibe 10 mg over-encapsulated tablets orally QD for 24 weeks and placebo (for alirocumab) SC injection Q2W for 24 weeks added to stable LMT.
arm group label: Alirocumab 75 mg/ up to 150 mg
arm group type: Experimental
description: Alirocumab 75 mg SC injection Q2W for 24 weeks and placebo (for atorvastatin/ezetimibe) over-encapsulated tablets orally QD for 24 weeks added to stable LMT. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on cardiovascular risk.
intervention type: Drug
intervention name: Atorvastatin
description: Atorvastatin over-encapsulated tablets.
arm group label: Atorvastatin (statin rechallenge arm)
intervention type: Drug
intervention name: Ezetimibe
description: Ezetimibe over-encapsulated tablet.
arm group label: Ezetimibe
other name: Zetia
intervention type: Drug
intervention name: Alirocumab
description: Alirocumab SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.
arm group label: Alirocumab 75 mg/ up to 150 mg
other name: REGN727/SAR236553
intervention type: Drug
intervention name: Placebo
description: Placebo for alirocumab, ezitimibe and atorvastatin.
arm group label: Alirocumab 75 mg/ up to 150 mg
arm group label: Atorvastatin (statin rechallenge arm)
arm group label: Ezetimibe
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trial Management
role: Study Director
affiliation: Regeneron Pharmaceuticals
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country: Austria
country: Canada
country: France
country: Israel
country: Italy
country: Norway
country: United Kingdom
country: United States
country: Germany
country: Netherlands
citation: Moriarty PM, Jacobson TA, Bruckert E, Thompson PD, Guyton JR, Baccara-Dinet MT, Gipe D. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol. 2014 Nov-Dec;8(6):554-561. doi: 10.1016/j.jacl.2014.09.007. Epub 2014 Sep 19.
PMID: 25499937
citation: Moriarty PM, Thompson PD, Cannon CP, Guyton JR, Bergeron J, Zieve FJ, Bruckert E, Jacobson TA, Kopecky SL, Baccara-Dinet MT, Du Y, Pordy R, Gipe DA; ODYSSEY ALTERNATIVE Investigators. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol. 2015 Nov-Dec;9(6):758-769. doi: 10.1016/j.jacl.2015.08.006. Epub 2015 Aug 29.
PMID: 26687696
responsible party type: Sponsor
mesh term: Hypercholesterolemia
mesh term: Atorvastatin
mesh term: Ezetimibe
mesh term: Alirocumab
participant flow: 
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reported events: 
certain agreements: 
point of contact: 