<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/NCT01670734</url>
  </required_header>
  <id_info>
    <org_study_id>POP12671</org_study_id>
    <secondary_id>2012-002292-33</secondary_id>
    <secondary_id>U1111-1129-0248</secondary_id>
    <nct_id>NCT01670734</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic and Tolerability of Alirocumab SAR236553 (REGN727) in Patients With Hepatic Impairment and in Healthy Subjects</brief_title>
  <official_title>An Open-Label, Pharmacokinetic and Tolerability Study of SAR236553/REGN727 Given as a Single SC Dose in Subjects With Mild and Moderate Hepatic Impairment, and in Matched Subjects With Normal Hepatic Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      Study the effect of mild or moderate hepatic impairment on the pharmacokinetics of alirocumab&#xD;
      SAR236553 (REGN727).&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  Assess the safety and tolerability of alirocumab SAR236553 (REGN727) in patients with&#xD;
           mild and moderate hepatic impairment and in matched subjects with normal hepatic&#xD;
           function.&#xD;
&#xD;
        -  Assess the pharmacodynamic profile of alirocumab SAR236553 (REGN727) in patients with&#xD;
           hepatic impairment and in matched subjects with normal hepatic function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Total duration of the study per subject (excluding screening) is about 12 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">May 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics: Assessment of serum concentrations of alirocumab SAR236553 (REGN727)</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of PK parameter - terminal elimination half-life (t1/2z) [</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PK parameter - apparent total body clearance (CL/F)</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PK parameter - Distribution volume at the steady-state (Vss/F)</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PK parameter - time to maximum concentration (tmax)</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PK parameter - Mean Residence Time (MRT [area])</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics: Change in LDL-C from baseline</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with Adverse Events</measure>
    <time_frame>Up to 12 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Hypercholesterolemia</condition>
  <arm_group>
    <arm_group_label>alirocumab SAR236553 (REGN727) - mild hepatic function</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Injection through subcutaneous (SC) administration in patients with mild hepatic function</description>
  </arm_group>
  <arm_group>
    <arm_group_label>alirocumab SAR236553 (REGN727) - moderate hepatic function</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Injection through subcutaneous (SC) administration in patients with moderate hepatic function</description>
  </arm_group>
  <arm_group>
    <arm_group_label>alirocumab SAR236553 (REGN727) - normal hepatic function</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Injection through subcutaneous (SC) administration in patients with normal hepatic function</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>alirocumab SAR236553 (REGN727)</intervention_name>
    <description>alirocumab SAR236553 (REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9)&#xD;
Pharmaceutical form:Solution for injection Route of administration: subcutaneous</description>
    <arm_group_label>alirocumab SAR236553 (REGN727) - mild hepatic function</arm_group_label>
    <arm_group_label>alirocumab SAR236553 (REGN727) - moderate hepatic function</arm_group_label>
    <arm_group_label>alirocumab SAR236553 (REGN727) - normal hepatic function</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          -  Male or female, between 18 to 75 years of age, inclusive.&#xD;
&#xD;
          -  Patients with mild and moderate hepatic impairment based on Child-Pugh score and&#xD;
             stable chronic liver disease.&#xD;
&#xD;
          -  Healthy subjects with normal hepatic function.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Patients with acute hepatitis, hepatic encephalopathy grade 2, 3, and 4.&#xD;
&#xD;
          -  Patients with history or presence of uncontrolled clinically relevant illness.&#xD;
&#xD;
          -  Healthy subjects with history or presence of clinically relevant illness.&#xD;
&#xD;
        The above information is not intended to contain all considerations relevant to a patient's&#xD;
        potential participation in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site Number 250001</name>
      <address>
        <city>Rennes</city>
        <zip>35000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 498001</name>
      <address>
        <city>Chisinau</city>
        <zip>2025</zip>
        <country>Moldova, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Moldova, Republic of</country>
  </location_countries>
  <verification_date>June 2013</verification_date>
  <study_first_submitted>August 16, 2012</study_first_submitted>
  <study_first_submitted_qc>August 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2012</study_first_posted>
  <last_update_submitted>June 27, 2013</last_update_submitted>
  <last_update_submitted_qc>June 27, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 28, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypercholesterolemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alirocumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01670734
org study id: POP12671
secondary id: 2012-002292-33
secondary id: U1111-1129-0248
nct id: NCT01670734
lead sponsor: 
collaborator: 
has dmc: No
Primary Objective:

      Study the effect of mild or moderate hepatic impairment on the pharmacokinetics of alirocumab
      SAR236553 (REGN727).

      Secondary Objectives:

        -  Assess the safety and tolerability of alirocumab SAR236553 (REGN727) in patients with
           mild and moderate hepatic impairment and in matched subjects with normal hepatic
           function.

        -  Assess the pharmacodynamic profile of alirocumab SAR236553 (REGN727) in patients with
           hepatic impairment and in matched subjects with normal hepatic function.
Total duration of the study per subject (excluding screening) is about 12 weeks.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Pharmacokinetics: Assessment of serum concentrations of alirocumab SAR236553 (REGN727)
time frame: Up to 12 weeks
measure: Assessment of PK parameter - terminal elimination half-life (t1/2z) [
time frame: Up to 12 weeks
measure: Assessment of PK parameter - apparent total body clearance (CL/F)
time frame: Up to 12 weeks
measure: Assessment of PK parameter - Distribution volume at the steady-state (Vss/F)
time frame: Up to 12 weeks
measure: Assessment of PK parameter - time to maximum concentration (tmax)
time frame: Up to 12 weeks
measure: Assessment of PK parameter - Mean Residence Time (MRT [area])
time frame: Up to 12 weeks
measure: Pharmacodynamics: Change in LDL-C from baseline
time frame: Up to 12 weeks
measure: Number of participants with Adverse Events
time frame: Up to 12 weeks
arm group label: alirocumab SAR236553 (REGN727) - mild hepatic function
arm group type: Experimental
description: Injection through subcutaneous (SC) administration in patients with mild hepatic function
arm group label: alirocumab SAR236553 (REGN727) - moderate hepatic function
arm group type: Experimental
description: Injection through subcutaneous (SC) administration in patients with moderate hepatic function
arm group label: alirocumab SAR236553 (REGN727) - normal hepatic function
arm group type: Experimental
description: Injection through subcutaneous (SC) administration in patients with normal hepatic function
intervention type: Drug
intervention name: alirocumab SAR236553 (REGN727)
description: alirocumab SAR236553 (REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9)
Pharmaceutical form:Solution for injection Route of administration: subcutaneous
arm group label: alirocumab SAR236553 (REGN727) - mild hepatic function
arm group label: alirocumab SAR236553 (REGN727) - moderate hepatic function
arm group label: alirocumab SAR236553 (REGN727) - normal hepatic function
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
facility: 
country: France
country: Moldova, Republic of
responsible party type: Sponsor
mesh term: Hypercholesterolemia
mesh term: Alirocumab