<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/NCT01709500</url>
  </required_header>
  <id_info>
    <org_study_id>R727-CL-1112</org_study_id>
    <nct_id>NCT01709500</nct_id>
  </id_info>
  <brief_title>Study of Alirocumab (REGN727/SAR236553) in Patients With heFH (Heterozygous Familial Hypercholesterolemia) Who Are Not Adequately Controlled With Their LMT (Lipid-Modifying Therapy)</brief_title>
  <acronym>ODYSSEY FH II</acronym>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of REGN727/SAR236553 in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy</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, placebo-controlled, parallel-group, multi-national study&#xD;
      alirocumab (REGN727/SAR236553) in patients with Heterozygous Familial Hypercholesterolemia&#xD;
      (heFH) who are not adequately controlled with their Lipid-Modifying Therapy (LMT).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">January 2015</completion_date>
  <primary_completion_date type="Actual">May 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 52</time_frame>
    <description>Calculated LDL-C values were obtained using the 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 52 regardless of status on- or off-treatment were used in the model.</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 52</time_frame>
    <description>Calculated LDL-C values were obtained using the 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 52 (i.e. up to 21 days after last injection) (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 52</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 52 regardless of status on- or off-treatment (ITT analysis).</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 52</time_frame>
    <description>Calculated LDL-C values were obtained using the 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 52 (i.e. up to 21 days after last injection) (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 52</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 52 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 52</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 52 (i.e. up to 21 days after last injection).</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 52</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 52 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 52</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 52 (i.e. up to 21 days after last injection).</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 52</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 52 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 52</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 52 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 52</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 52 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 52</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 52 regardless of status on- or off treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis</measure>
    <time_frame>From Baseline to Week 52</time_frame>
    <description>Calculated LDL-C values were obtained using the Friedewald formula. Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off treatment (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 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 52</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 52 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 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 52</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 52 i.e. up to 21 days after last injection (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 52</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 52 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 52 - On-Treatment Analysis</measure>
    <time_frame>Up to Week 52</time_frame>
    <description>Adjusted percentages at Week 52 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection (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 52</time_frame>
    <description>Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 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 52</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 52 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 52</time_frame>
    <description>Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 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 52</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 52 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 52</time_frame>
    <description>Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis</measure>
    <time_frame>From Baseline to Week 52</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 52 regardless of status on-or off-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis</measure>
    <time_frame>From Baseline to Week 52</time_frame>
    <description>Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 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 52</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 52 regardless of status on-or off-treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">249</enrollment>
  <condition>Heterozygous Familial Hypercholesterolemia</condition>
  <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 every two weeks (Q2W) added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LMT (atorvastatin, simvastatin, or rosuvastatin)</intervention_name>
    <arm_group_label>Alirocumab 75 mg/up to 150 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>alirocumab</intervention_name>
    <description>Alirocumab administered as a subcutaneous (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</other_name>
    <other_name>SAR236553</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo matched to alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with heFH* who are not adequately controlled** with a maximally-tolerated&#xD;
             daily dose*** of statin with or without other LMT, at a stable dose prior to the&#xD;
             screening visit (week -2).&#xD;
&#xD;
             *Diagnosis of heFH must be made either by genotyping or by clinical criteria. For&#xD;
             those patients not genotyped, the clinical diagnosis may be based on either the Simon&#xD;
             Broome criteria for definite FH (Appendix 1) or the WHO/Dutch Lipid Network criteria&#xD;
             with a score of &gt;8 points (Appendix 2).&#xD;
&#xD;
             ** &quot;Not adequately controlled&quot; is defined as LDL-C ≥70 mg/dL (1.81 mmol/L) at the&#xD;
             screening visit (week -2) in patients with a history of documented CVD (Appendix 3),&#xD;
             or LDL-C ≥100 mg/dL (2.59 mmol/L) at the screening visit (week -2) in patients without&#xD;
             a history of documented CVD.&#xD;
&#xD;
             *** &quot;Maximally-tolerated dose&quot; is defined as (any of the following are acceptable):&#xD;
&#xD;
               -  Rosuvastatin 20 mg or 40 mg daily&#xD;
&#xD;
               -  Atorvastatin 40 mg or 80 mg daily&#xD;
&#xD;
               -  Simvastatin 80 mg daily (if already on this dose for &gt;1 year - see exclusion&#xD;
                  criterion #7)&#xD;
&#xD;
             Note: Patients who are not able to be on any of the above statin doses should be&#xD;
             treated with the dose of daily atorvastatin, rosuvastatin, or simvastatin which is&#xD;
             considered appropriate for the patient, according to the investigator's judgment. Some&#xD;
             examples of acceptable reasons for a patient taking a lower statin dose include, but&#xD;
             are not limited to: adverse effects on higher doses, advanced age, low body mass&#xD;
             index, regional practices, local prescribing information, concomitant medications,&#xD;
             co-morbid conditions such as impaired glucose tolerance/impaired fasting glucose. The&#xD;
             reason(s) will be documented in the case report form (CRF).&#xD;
&#xD;
          2. Provide signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient without diagnosis of heFH made either by genotyping or by clinical criteria&#xD;
&#xD;
          2. LDL-C &lt;70 mg/dL (&lt;1.81 mmol/L) at the screening visit (week-2) in patients with&#xD;
             history of documented cardiovascular disease&#xD;
&#xD;
          3. LDL-C &lt;100 mg/dL (&lt;2.59 mmol/L) at the screening visit (week -2) in patients without&#xD;
             history of documented cardiovascular disease&#xD;
&#xD;
          4. Not on a stable dose of LMT (including statin) for at least 4 weeks and/or fenofibrate&#xD;
             for at least 6 weeks, as applicable, prior to the screening visit (week -2) and from&#xD;
             screening to randomization&#xD;
&#xD;
          5. Currently taking another statin than simvastatin, atorvastatin, or rosuvastatin&#xD;
&#xD;
          6. Simvastatin, atorvastatin, or rosuvastatin is not taken daily or not taken at a&#xD;
             registered dose&#xD;
&#xD;
          7. Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg (except&#xD;
             for patients on simvastatin 80 mg for more than 1 year, who are eligible)&#xD;
&#xD;
          8. Use of fibrates, other than fenofibrate within 6 weeks of the screening visit (week-2)&#xD;
             or between screening and randomization visits&#xD;
&#xD;
          9. Use of nutraceutical products or over-the-counter therapies that may affect lipids&#xD;
             which have not been at a stable dose/amount for at least 4 weeks prior to the&#xD;
             screening visit (week -2) or between screening and randomization visits&#xD;
&#xD;
         10. Use of red yeast rice products within 4 weeks of the screening visit (week-2), or&#xD;
             between screening and randomization visits&#xD;
&#xD;
         11. Patient who has received plasmapheresis treatment within 2 months prior to the&#xD;
             screening visit (week -2), or has plans to receive it during the study&#xD;
&#xD;
         12. Recent (within 3 months prior to the screening visit [week -2] or between screening&#xD;
             and randomization visits) MI, unstable angina leading to hospitalization, percutaneous&#xD;
             coronary intervention (PCI), coronary artery bypass graft surgery (CABG), uncontrolled&#xD;
             cardiac arrhythmia, stroke, transient ischemic attack (TIA), carotid&#xD;
             revascularization, endovascular procedure or surgical intervention for peripheral&#xD;
             vascular disease&#xD;
&#xD;
        (The inclusion/exclusion criteria provided above is not intended to contain all&#xD;
        considerations relevant to a participant'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>Hradec Kralove</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha 2</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha 5</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha 8</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Trutnov</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Vyskov</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Alkmaar</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Apeldoorn</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Enschede</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Goes</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hoogeveen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hoorn</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sittard- Geleen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Utrecht (2 locations)</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Venlo</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Waalwijk</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cardiff</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Middlesex</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Newcastle upon Tyne</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>West Bromwich</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czech Republic</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2015</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>September 29, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 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>September 29, 2015</last_update_submitted>
  <last_update_submitted_qc>September 29, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 28, 2015</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>Hyperlipoproteinemia Type II</mesh_term>
    <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>Rosuvastatin Calcium</mesh_term>
    <mesh_term>Simvastatin</mesh_term>
    <mesh_term>Alirocumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 26 sites in 4 countries. Overall, 322 participants were screened between 28 Nov 2012 and 26 Apr 2013, 73 of whom were screen failures.</recruitment_details>
      <pre_assignment_details>Randomization was stratified according to prior history of myocardial infarction or ischemic stroke, and intensity of statin treatment. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 2:1 (alirocumab: placebo) ratio after confirmation of selection criteria.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Alirocumab 75 mg/up to 150 mg</title>
          <description>Alirocumab 75 mg SC injection every two weeks (Q2W) added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="167"/>
                <participants group_id="P2" count="82"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="167"/>
                <participants group_id="P2" count="81"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="167"/>
                <participants group_id="P2" count="82"/>
              </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_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="1"/>
              </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="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Related to IMP administration</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Treatment ongoing</title>
              <participants_list>
                <participants group_id="P1" count="156"/>
                <participants group_id="P2" count="78"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Alirocumab 75 mg/up to 150 mg</title>
          <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo matched to alirocumab SC injection for 78--week treatment duration.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="167"/>
            <count group_id="B2" value="82"/>
            <count group_id="B3" value="249"/>
          </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="53.2" spread="12.93"/>
                    <measurement group_id="B2" value="53.2" spread="12.55"/>
                    <measurement group_id="B3" value="53.2" spread="12.8"/>
                  </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="81"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="118"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="86"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Calculated LDL-C in mmol/L</title>
          <description>Calculated LDL-C values were obtained using 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="3.485" spread="1.065"/>
                    <measurement group_id="B2" value="3.471" spread="1.071"/>
                    <measurement group_id="B3" value="3.480" spread="1.065"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Calculated LDL-C in mg/dL</title>
          <description>Calculated LDL-C values were obtained using 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="134.6" spread="41.1"/>
                    <measurement group_id="B2" value="134.0" spread="41.4"/>
                    <measurement group_id="B3" value="134.4" spread="41.1"/>
                  </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 using the 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 52 regardless of status on- or off-treatment were used in the model.</description>
        <time_frame>From Baseline to Week 52</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>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 using the 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 52 regardless of status on- or off-treatment were used in the model.</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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-48.7" spread="1.9"/>
                    <measurement group_id="O2" value="2.8" spread="2.8"/>
                  </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 placebo group using an appropriate contrast statement.</groups_desc>
            <non_inferiority_type>Superiority or Other</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>-51.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-58.1</ci_lower_limit>
            <ci_upper_limit>-44.8</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 using the 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 52 (i.e. up to 21 days after last injection) (on-treatment analysis).</description>
        <time_frame>From Baseline to Week 52</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>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 using the 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 52 (i.e. up to 21 days after last injection) (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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-49.4" spread="1.9"/>
                    <measurement group_id="O2" value="2.7" spread="2.7"/>
                  </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>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</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>-52.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-58.7</ci_lower_limit>
            <ci_upper_limit>-45.6</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>Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment (ITT analysis).</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Calculated LDL-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 52 regardless of status on- or off-treatment (ITT analysis).</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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-43.8" spread="1.8"/>
                    <measurement group_id="O2" value="4.6" spread="2.6"/>
                  </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</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>-48.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-54.7</ci_lower_limit>
            <ci_upper_limit>-42.2</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 using the 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 52 (i.e. up to 21 days after last injection) (on-treatment analysis).</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 using the 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 52 (i.e. up to 21 days after last injection) (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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-44.2" spread="1.8"/>
                    <measurement group_id="O2" value="4.6" spread="2.6"/>
                  </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</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>-48.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-55</ci_lower_limit>
            <ci_upper_limit>-42.5</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 52 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 52</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>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 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="163"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-42.8" spread="1.4"/>
                    <measurement group_id="O2" value="-3.5" spread="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</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>-39.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-44.1</ci_lower_limit>
            <ci_upper_limit>-34.5</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 52 (i.e. up to 21 days after last injection).</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>mITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 (i.e. up to 21 days after last injection).</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="162"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-43.2" spread="1.4"/>
                    <measurement group_id="O2" value="-3.5" spread="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</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>-39.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-44.5</ci_lower_limit>
            <ci_upper_limit>-35.1</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 52 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 52</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>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-42.6" spread="1.8"/>
                    <measurement group_id="O2" value="3.1" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</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</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>-45.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-51.8</ci_lower_limit>
            <ci_upper_limit>-39.7</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 52 (i.e. up to 21 days after last injection).</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>mITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 (i.e. up to 21 days after last injection).</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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-43.2" spread="1.7"/>
                    <measurement group_id="O2" value="3.1" spread="2.5"/>
                  </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</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>-46.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-52.3</ci_lower_limit>
            <ci_upper_limit>-40.4</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 52 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 52</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>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-30.6" spread="1.4"/>
                    <measurement group_id="O2" value="2.1" 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</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>-32.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-37.4</ci_lower_limit>
            <ci_upper_limit>-28.1</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 52 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>Apo B ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 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="163"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-35.4" spread="1.4"/>
                    <measurement group_id="O2" value="-0.9" spread="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</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>-34.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-39.2</ci_lower_limit>
            <ci_upper_limit>-29.8</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 52 regardless of status on- or off-treatment.</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>Non-HDL-C ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-37.9" spread="1.7"/>
                    <measurement group_id="O2" value="4.1" 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).</groups_desc>
            <non_inferiority_type>Superiority or Other</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>-42</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-47.8</ci_lower_limit>
            <ci_upper_limit>-36.2</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 52 regardless of status on- or off treatment.</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>Total--C ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-26.6" spread="1.3"/>
                    <measurement group_id="O2" value="3.4" 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</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Threshold for significance ≤ 0.05.</method_desc>
            <param_type>LS Mean Difference</param_type>
            <param_value>-29.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-34.5</ci_lower_limit>
            <ci_upper_limit>-25.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis</title>
        <description>Calculated LDL-C values were obtained using the Friedewald formula. Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off treatment (ITT analysis).</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis</title>
          <description>Calculated LDL-C values were obtained using the Friedewald formula. Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off treatment (ITT analysis).</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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-50.3" spread="2.3"/>
                    <measurement group_id="O2" value="8.4" spread="3.3"/>
                  </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</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>-58.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-66.8</ci_lower_limit>
            <ci_upper_limit>-50.8</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 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 52 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).</description>
        <time_frame>Up to Week 52</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 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 52 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.4"/>
                    <measurement group_id="O2" value="11.3"/>
                  </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). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other</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>52.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>20.9</ci_lower_limit>
            <ci_upper_limit>130</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 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 52 i.e. up to 21 days after last injection (on-treatment analysis).</description>
        <time_frame>Up to week 52</time_frame>
        <population>mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 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 52 i.e. up to 21 days after last injection (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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.1"/>
                    <measurement group_id="O2" value="11.6"/>
                  </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</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>53.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>21.4</ci_lower_limit>
            <ci_upper_limit>132.6</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 52 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).</description>
        <time_frame>Up to Week 52</time_frame>
        <population>ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.2"/>
                    <measurement group_id="O2" value="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). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other</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>239.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>31.6</ci_lower_limit>
            <ci_upper_limit>1820.3</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 52 - On-Treatment Analysis</title>
        <description>Adjusted percentages at Week 52 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection (on-treatment analysis).</description>
        <time_frame>Up to Week 52</time_frame>
        <population>mITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Reaching Calculated LDL--C &lt;70 mg/dL (1.81 mmol/L) at Week 52 - On-Treatment Analysis</title>
          <description>Adjusted percentages at Week 52 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection (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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.8"/>
                    <measurement group_id="O2" value="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). Statistical analysis used a multiple imputation approach followed by a Logistic regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other</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>240.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>31.4</ci_lower_limit>
            <ci_upper_limit>1841.7</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>Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>Participants analyzed: participants of the ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis</title>
          <description>Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-30.3" spread="1.8"/>
                    <measurement group_id="O2" value="-10" spread="2.5"/>
                  </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 multiple imputation approach followed by a robust regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other</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>-20.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-26.4</ci_lower_limit>
            <ci_upper_limit>-14.2</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 52 regardless of status on-or off-treatment.</description>
        <time_frame>From Baseline to Week 52</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>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="1.2"/>
                    <measurement group_id="O2" value="-0.8" spread="1.6"/>
                  </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</non_inferiority_type>
            <p_value>= 0.0009</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>6.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.8</ci_lower_limit>
            <ci_upper_limit>10.7</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>Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>Participants analyzed: participants of the ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis</title>
          <description>Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.4" spread="2"/>
                    <measurement group_id="O2" value="0.5" spread="2.8"/>
                  </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. Statistical analysis used a multiple imputation approach followed by a robust regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>= 0.0012</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>-10.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-17.5</ci_lower_limit>
            <ci_upper_limit>-4.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </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 52 regardless of status on-or off-treatment.</description>
        <time_frame>From Baseline to Week 52</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>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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 52 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="163"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="0.9"/>
                    <measurement group_id="O2" value="-1.6" 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</non_inferiority_type>
            <p_value>= 0.0062</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>4.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.3</ci_lower_limit>
            <ci_upper_limit>7.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis</title>
        <description>Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>Lipoprotein (a) ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis</title>
          <description>Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.</description>
          <population>Lipoprotein (a) 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-24.7" spread="1.7"/>
                    <measurement group_id="O2" value="-5.6" spread="2.5"/>
                  </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 multiple imputation approach followed by a robust regression model.</groups_desc>
            <non_inferiority_type>Superiority or Other</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>-19.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-25</ci_lower_limit>
            <ci_upper_limit>-13.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in 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 52 regardless of status on-or off-treatment.</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>HDL-C ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in 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 52 regardless of status on-or off-treatment.</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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="1.0"/>
                    <measurement group_id="O2" value="-0.8" spread="1.6"/>
                  </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</non_inferiority_type>
            <p_value>= 0.0147</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>4.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.9</ci_lower_limit>
            <ci_upper_limit>7.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis</title>
        <description>Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>Fasting triglycerides ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis</title>
          <description>Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 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="166"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.1" spread="2.2"/>
                    <measurement group_id="O2" value="0.6" spread="3.1"/>
                  </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</non_inferiority_type>
            <p_value>= 0.024</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>-8.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-16.1</ci_lower_limit>
            <ci_upper_limit>-1.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Apo A-1 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 52 regardless of status on-or off-treatment.</description>
        <time_frame>From Baseline to Week 52</time_frame>
        <population>Apo A-1 ITT population.</population>
        <group_list>
          <group group_id="O1">
            <title>Alirocumab 75 mg/up to 150 mg</title>
            <description>Alirocumab 75 mg SC injection Q2W added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Apo A-1 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 52 regardless of status on-or off-treatment.</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="163"/>
                <count group_id="O2" value="81"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="0.9"/>
                    <measurement group_id="O2" value="-1.9" 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</non_inferiority_type>
            <p_value>= 0.1475</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>2.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.8</ci_lower_limit>
            <ci_upper_limit>5.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Baseline up to Week 78</time_frame>
      <desc>Treatment emergent adverse events that developed during treatment emergent adverse events period (the time from the first dose of study drug to the last dose of study drug + 70 days (10 weeks) are reported.</desc>
      <group_list>
        <group group_id="E1">
          <title>Alirocumab 75 mg/up to 150 mg</title>
          <description>Alirocumab 75 mg SC injection every two weeks (Q2W) added to stable dose of statin with or without LMT for 76 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo matched to alirocumab SC injection for 78-week treatment duration.</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="10" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Cardiogenic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Coronary artery stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Device dislocation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Non-Cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Endocarditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Hepatitis a</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Lumbar vertebral fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Rectal adenocarcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </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="65" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="167"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="81"/>
              </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 Management</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/NCT01709500
org study id: R727-CL-1112
nct id: NCT01709500
lead sponsor: 
collaborator: 
has dmc: Yes
This is a randomized, double-blind, placebo-controlled, parallel-group, multi-national study
      alirocumab (REGN727/SAR236553) in patients with Heterozygous Familial Hypercholesterolemia
      (heFH) who are not adequately controlled with their Lipid-Modifying Therapy (LMT).
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 52
description: Calculated LDL-C values were obtained using the 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 52 regardless of status on- or off-treatment were used in the model.
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
time frame: From Baseline to Week 52
description: Calculated LDL-C values were obtained using the 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 52 (i.e. up to 21 days after last injection) (on-treatment analysis).
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
time frame: From Baseline to Week 52
description: Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment (ITT analysis).
measure: Percent Change From Baseline in Calculated LDL-C at Week 12 - On- Treatment Analysis
time frame: From Baseline to Week 52
description: Calculated LDL-C values were obtained using the 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 52 (i.e. up to 21 days after last injection) (on-treatment analysis).
measure: Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
time frame: From Baseline to Week 52
description: Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 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 52
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 52 (i.e. up to 21 days after last injection).
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 52
description: Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 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 52
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 52 (i.e. up to 21 days after last injection).
measure: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
time frame: From Baseline to Week 52
description: Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 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 52
description: Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 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 52
description: Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 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 52
description: Adjusted LS means and standard errors at Week 12 from MMRM model including all available post baseline data from Week 4 to Week 52 regardless of status on- or off treatment.
measure: Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis
time frame: From Baseline to Week 52
description: Calculated LDL-C values were obtained using the Friedewald formula. Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off treatment (ITT analysis).
measure: Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) 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 52
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 52 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 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 52
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 52 i.e. up to 21 days after last injection (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 52
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 52 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 52 - On-Treatment Analysis
time frame: Up to Week 52
description: Adjusted percentages at Week 52 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection (on-treatment analysis).
measure: Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
time frame: From Baseline to Week 52
description: Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 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 52
description: Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 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 52
description: Adjusted means and standard errors at Week 24 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 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 52
description: Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 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 52
description: Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
measure: Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
time frame: From Baseline to Week 52
description: Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
measure: Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
time frame: From Baseline to Week 52
description: Adjusted means and standard errors at Week 12 from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 52 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 52
description: Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
arm group label: Alirocumab 75 mg/up to 150 mg
arm group type: Experimental
description: Alirocumab 75 mg every two weeks (Q2W) added to stable dose of statin with or without LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL at Week 8.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo matched to alirocumab SC injection for 78-week treatment duration.
intervention type: Drug
intervention name: LMT (atorvastatin, simvastatin, or rosuvastatin)
arm group label: Alirocumab 75 mg/up to 150 mg
intervention type: Drug
intervention name: alirocumab
description: Alirocumab administered as a subcutaneous (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
other name: SAR236553
intervention type: Drug
intervention name: Placebo
description: Placebo matched to alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.
arm group label: Placebo
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: Czech Republic
country: Netherlands
country: Norway
country: United Kingdom
responsible party type: Sponsor
mesh term: Hyperlipoproteinemia Type II
mesh term: Hypercholesterolemia
mesh term: Atorvastatin
mesh term: Rosuvastatin Calcium
mesh term: Simvastatin
mesh term: Alirocumab
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