<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/NCT03814187</url>
  </required_header>
  <id_info>
    <org_study_id>MDCO-PCS-17-05</org_study_id>
    <secondary_id>CKJX839A12306B</secondary_id>
    <secondary_id>2017-003092-55</secondary_id>
    <nct_id>NCT03814187</nct_id>
  </id_info>
  <brief_title>Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C</brief_title>
  <acronym>ORION-8</acronym>
  <official_title>An Open-label Extension Trial of the Phase III Lipid-lowering Trials to Assess the Effect of Long Term Dosing of Inclisiran Given as Subcutaneous Injections in Subjects With High Cardiovascular Risk and Elevated LDL-C</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this extension study is to evaluate the efficacy, safety, and tolerability of&#xD;
      long-term dosing of Inclisiran. The study will be a global multicenter study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be an open label, long term extension study in subjects with atherosclerotic&#xD;
      cardiovascular disease (ASCVD), ASCVD-risk equivalents (eg, diabetes and familial&#xD;
      hypercholesterolemia), or heterozygous or homozygous familial hypercholesterolemia (HeFH or&#xD;
      HoFH) and elevated low density lipoprotein cholesterol (LDL-C) despite maximum tolerated dose&#xD;
      of LDL-C lowering therapies who have completed the inclisiran Phase II trial MDCO-PCS-16-01&#xD;
      (ORION-3), or any of the following Phase III lipid lowering studies: MDCO-PCS-17-03&#xD;
      (ORION-9), MDCO-PCS-17-4 (ORION-10), or MDCO-PCS-17-08 (ORION-11)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 16, 2019</start_date>
  <completion_date type="Actual">February 13, 2023</completion_date>
  <primary_completion_date type="Actual">February 13, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of subjects achieving prespecified LDL-C targets.</measure>
    <time_frame>Day 1080</time_frame>
    <description>A primary objective of the study is to evaluate the effect of inclisiran treatment on the proportion of subjects achieving prespecified LDL-C targets at end of study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Adverse Events and Serious Adverse Events</measure>
    <time_frame>Baseline, Day 1080</time_frame>
    <description>Safety assessments include adverse events and serious adverse events for long-term safety profile</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absolute and percentage change in LDL-C from baseline.</measure>
    <time_frame>Baseline, Day 1080</time_frame>
    <description>A secondary objective of this study is to evaluate the effect of inclisiran on LDL-C levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute and percentage change in other lipids and lipoprotein from baseline.</measure>
    <time_frame>Baseline, Day 1080</time_frame>
    <description>A secondary objective of this study is to evaluate the effect of inclisiran on other lipids and lipoproteins.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3275</enrollment>
  <condition>ASCVD</condition>
  <condition>Elevated Cholesterol</condition>
  <condition>Heterozygous Familial Hypercholesterolemia</condition>
  <condition>Homozygous Familial Hypercholesterolemia</condition>
  <arm_group>
    <arm_group_label>Inclisiran</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Inclisiran sodium 300 milligrams (mg) will be administered as a single SC injection on Day 1*, 90, then every 180 days to Day 990.&#xD;
*Subjects who received blinded placebo in the feeder study will receive blinded inclisiran and subjects who received blinded inclisiran in the feeder study will receive blinded placebo on Day 1 in ORION-8. Subjects from the open label ORION-3 study will not receive any injection of study drug on Day 1. Their first dose of study medication will be at day 90</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inclisiran Sodium</intervention_name>
    <description>Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.</description>
    <arm_group_label>Inclisiran</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Completion on a previously qualifying inclisiran Phase II trial MDCO-PCS-16-01&#xD;
             (ORION-3), or Phase III lipid lowering ORION feeder study [MDCO-PCS-17-03 (ORION-9),&#xD;
             MDCO-PCS-17-4 (ORION-10), or MDCO-PCS-17-08 (ORION-11)] meaning the subject received&#xD;
             the last dose of study drug and completed the final study visit per applicable&#xD;
             protocol.&#xD;
&#xD;
          2. On current lipid-lowering therapies (such as a statin and/or ezetimibe) from previous&#xD;
             study with no planned medication or dose change during study participation.&#xD;
&#xD;
          3. Willing and able to give informed consent before initiation of any study-related&#xD;
             procedures and willing to comply with all required study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any uncontrolled or serious disease, or any medical or surgical condition, that may&#xD;
             either interfere with participation in the clinical study, and/or put the subject at&#xD;
             significant risk [according to investigator's (or delegate's) judgment] if he/she&#xD;
             participates in the clinical study.&#xD;
&#xD;
          2. An underlying known disease, or surgical, physical, or medical condition that, in the&#xD;
             opinion of the investigator (or delegate) might interfere with interpretation of the&#xD;
             clinical study results.&#xD;
&#xD;
          3. Severe concomitant noncardiovascular disease that carries the risk of reducing life&#xD;
             expectancy to less than 3 years,&#xD;
&#xD;
          4. Active liver disease defined as any known current infectious, neoplastic, or metabolic&#xD;
             pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate&#xD;
             aminotransferase (AST), elevation &gt;3x the upper limit of normal (ULN), or total&#xD;
             bilirubin (TBIL) elevation &gt;2x ULN at the last recorded visit in the feeder study&#xD;
             prior to study entry visit.&#xD;
&#xD;
          5. Females who are pregnant or nursing, or who are of childbearing potential and&#xD;
             unwilling to use at least one method of acceptable effective contraception (eg, oral&#xD;
             contraceptives, barrier methods, approved contraceptive implant, long-term injectable&#xD;
             contraception, intrauterine device) for the entire duration of the study. Exemptions&#xD;
             from this criterion:&#xD;
&#xD;
               1. Women &gt;2 years postmenopausal (defined as 1 year or longer since last menstrual&#xD;
                  period) and more than 55 years of age.&#xD;
&#xD;
               2. Postmenopausal women (as defined above) and less than 55 years of age with a&#xD;
                  negative pregnancy test within 24 hours of randomization.&#xD;
&#xD;
               3. Women who are surgically sterilized at least 3 months prior to enrollment.&#xD;
&#xD;
          6. Planned use of other investigational medicinal products other than inclisiran or&#xD;
             devices during the course of the study.&#xD;
&#xD;
          7. Any condition that according to the investigator could interfere with the conduct of&#xD;
             the study, such as but not limited to:&#xD;
&#xD;
               1. Subjects who are unable to communicate or to cooperate with the investigator&#xD;
&#xD;
               2. Unable to understand the protocol requirements, instructions and study-related&#xD;
                  restrictions, the nature, scope, and possible consequences of the study&#xD;
                  (including subjects whose cooperation is doubtful due to drug abuse or alcohol&#xD;
                  dependency)&#xD;
&#xD;
               3. Unlikely to comply with the protocol requirements, instructions, and&#xD;
                  study-related restrictions (eg, uncooperative attitude, inability to return for&#xD;
                  follow-up visits, and improbability of completing the study)&#xD;
&#xD;
               4. Have any medical or surgical condition, which in the opinion of the investigator&#xD;
                  would put the subject at increased risk from participating in the study&#xD;
&#xD;
               5. Persons directly involved in the conduct of the study.&#xD;
&#xD;
        The above information is not intended to contain all considerations relevant to a&#xD;
        participant's potential participation in a 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>Scott Wright, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site 10001-015</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-138</name>
      <address>
        <city>Foley</city>
        <state>Alabama</state>
        <zip>36535</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-113</name>
      <address>
        <city>Huntsville</city>
        <state>Alabama</state>
        <zip>35801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-058</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-037</name>
      <address>
        <city>Montgomery</city>
        <state>Alabama</state>
        <zip>36117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-076</name>
      <address>
        <city>Saraland</city>
        <state>Alabama</state>
        <zip>36571</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-013</name>
      <address>
        <city>Chandler</city>
        <state>Arizona</state>
        <zip>85224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-077</name>
      <address>
        <city>Mesa</city>
        <state>Arizona</state>
        <zip>85213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-136</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-051</name>
      <address>
        <city>Surprise</city>
        <state>Arizona</state>
        <zip>85374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-019</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-004</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-132</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85745</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-073</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-050</name>
      <address>
        <city>Canoga Park</city>
        <state>California</state>
        <zip>91303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-011</name>
      <address>
        <city>Carlsbad</city>
        <state>California</state>
        <zip>92008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-065</name>
      <address>
        <city>El Cajon</city>
        <state>California</state>
        <zip>92020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-150</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90001-005</name>
      <address>
        <city>Mission Viejo</city>
        <state>California</state>
        <zip>92691</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-043</name>
      <address>
        <city>Northridge</city>
        <state>California</state>
        <zip>91324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-022</name>
      <address>
        <city>Northridge</city>
        <state>California</state>
        <zip>91325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-033</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95821-2134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-105</name>
      <address>
        <city>San Ramon</city>
        <state>California</state>
        <zip>94582</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-008</name>
      <address>
        <city>Santa Rosa</city>
        <state>California</state>
        <zip>95405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-153</name>
      <address>
        <city>Spring Valley</city>
        <state>California</state>
        <zip>91978</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90001-015</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-044</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90001-047</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33434</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-084</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-155</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-099</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33761</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-127</name>
      <address>
        <city>Daytona Beach</city>
        <state>Florida</state>
        <zip>32117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-119</name>
      <address>
        <city>Fleming Island</city>
        <state>Florida</state>
        <zip>32003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-070</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-067</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-139</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-039</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-098</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-080</name>
      <address>
        <city>Miami Springs</city>
        <state>Florida</state>
        <zip>33166</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-081</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-140</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-142</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-030</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33165</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-116</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33183</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-027</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-115</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-048</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-147</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-003</name>
      <address>
        <city>Pinellas Park</city>
        <state>Florida</state>
        <zip>33781</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-104</name>
      <address>
        <city>Ponte Vedra</city>
        <state>Florida</state>
        <zip>32081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-090</name>
      <address>
        <city>Saint Augustine</city>
        <state>Florida</state>
        <zip>32086</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-102</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-123</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239-3513</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-143</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-069</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-137</name>
      <address>
        <city>Dunwoody</city>
        <state>Georgia</state>
        <zip>30338</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-092</name>
      <address>
        <city>Macon</city>
        <state>Georgia</state>
        <zip>31210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-059</name>
      <address>
        <city>Arlington Heights</city>
        <state>Illinois</state>
        <zip>60005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-158</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60652</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-036</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-082</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-040</name>
      <address>
        <city>Valparaiso</city>
        <state>Indiana</state>
        <zip>46383</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-074</name>
      <address>
        <city>West Des Moines</city>
        <state>Iowa</state>
        <zip>50266</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-028</name>
      <address>
        <city>Hutchinson</city>
        <state>Kansas</state>
        <zip>67502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-125</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-108</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-107</name>
      <address>
        <city>Owensboro</city>
        <state>Kentucky</state>
        <zip>42303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-144</name>
      <address>
        <city>Crowley</city>
        <state>Louisiana</state>
        <zip>70526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-041</name>
      <address>
        <city>Lake Charles</city>
        <state>Louisiana</state>
        <zip>70601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-101</name>
      <address>
        <city>Monroe</city>
        <state>Louisiana</state>
        <zip>71201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90001-004</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-024</name>
      <address>
        <city>Flint</city>
        <state>Michigan</state>
        <zip>48504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-095</name>
      <address>
        <city>Grandville</city>
        <state>Michigan</state>
        <zip>49418</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-078</name>
      <address>
        <city>Sterling Heights</city>
        <state>Michigan</state>
        <zip>48310</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-034</name>
      <address>
        <city>Troy</city>
        <state>Michigan</state>
        <zip>48098</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-018</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90001-056</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-156</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-007</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90001-012</name>
      <address>
        <city>Butte</city>
        <state>Montana</state>
        <zip>59701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-053</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-021</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90001-112</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-124</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-060</name>
      <address>
        <city>Bridgewater</city>
        <state>New Jersey</state>
        <zip>08807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90001-014</name>
      <address>
        <city>Summit</city>
        <state>New Jersey</state>
        <zip>07901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-055</name>
      <address>
        <city>Warren</city>
        <state>New Jersey</state>
        <zip>07059</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-054</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-122</name>
      <address>
        <city>Binghamton</city>
        <state>New York</state>
        <zip>13901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-128</name>
      <address>
        <city>Endwell</city>
        <state>New York</state>
        <zip>13760</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-042</name>
      <address>
        <city>New Windsor</city>
        <state>New York</state>
        <zip>12553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-129</name>
      <address>
        <city>Poughkeepsie</city>
        <state>New York</state>
        <zip>12601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-110</name>
      <address>
        <city>Williamsville</city>
        <state>New York</state>
        <zip>14221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-063</name>
      <address>
        <city>Cary</city>
        <state>North Carolina</state>
        <zip>27518</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-064</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-145</name>
      <address>
        <city>Mooresville</city>
        <state>North Carolina</state>
        <zip>28117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-046</name>
      <address>
        <city>Shelby</city>
        <state>North Carolina</state>
        <zip>28150</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-016</name>
      <address>
        <city>Akron</city>
        <state>Ohio</state>
        <zip>443311</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-120</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90001-002</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-010</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-134</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-014</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-141</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45419</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-148</name>
      <address>
        <city>Marion</city>
        <state>Ohio</state>
        <zip>43302</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-109</name>
      <address>
        <city>Wyomissing</city>
        <state>Pennsylvania</state>
        <zip>19610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-001</name>
      <address>
        <city>Anderson</city>
        <state>South Carolina</state>
        <zip>29621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-006</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29651</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-075.</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29651</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-111</name>
      <address>
        <city>Myrtle Beach</city>
        <state>South Carolina</state>
        <zip>29588</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-133</name>
      <address>
        <city>Pelzer</city>
        <state>South Carolina</state>
        <zip>29669</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-103</name>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <zip>57701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-146</name>
      <address>
        <city>Athens</city>
        <state>Tennessee</state>
        <zip>37303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-130</name>
      <address>
        <city>Kingsport</city>
        <state>Tennessee</state>
        <zip>37660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-118</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-106</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37917</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-100</name>
      <address>
        <city>Amarillo</city>
        <state>Texas</state>
        <zip>79106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-087</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78726</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-117</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-009</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-068</name>
      <address>
        <city>Edinburg</city>
        <state>Texas</state>
        <zip>78503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-031</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77002</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-088</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-091</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-061</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77058</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-032</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77070</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-057</name>
      <address>
        <city>New Braunfels</city>
        <state>Texas</state>
        <zip>78130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-079</name>
      <address>
        <city>Round Rock</city>
        <state>Texas</state>
        <zip>78681</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-071</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-083</name>
      <address>
        <city>Schertz</city>
        <state>Texas</state>
        <zip>78154</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-149</name>
      <address>
        <city>Shavano Park</city>
        <state>Texas</state>
        <zip>78231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-045</name>
      <address>
        <city>Tomball</city>
        <state>Texas</state>
        <zip>77375</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-005</name>
      <address>
        <city>Layton</city>
        <state>Utah</state>
        <zip>84041</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-002</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-052</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>94107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-093</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-085</name>
      <address>
        <city>Manassas</city>
        <state>Virginia</state>
        <zip>20110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-094</name>
      <address>
        <city>Midlothian</city>
        <state>Virginia</state>
        <zip>23114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-023</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-029</name>
      <address>
        <city>Suffolk</city>
        <state>Virginia</state>
        <zip>23435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 10001-114</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90011-005</name>
      <address>
        <city>Chicoutimi</city>
        <state>Quebec</state>
        <zip>G7H 7K9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90011-001</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2W 1R7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90011-002</name>
      <address>
        <city>Québec</city>
        <state>Quebec</state>
        <zip>GIV 4W2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11420-002</name>
      <address>
        <city>Chomutov</city>
        <zip>430 02</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90420-001</name>
      <address>
        <city>Praha</city>
        <zip>140 21</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90420-006</name>
      <address>
        <city>Praha</city>
        <zip>180 81</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11420-003</name>
      <address>
        <city>Uherské Hradiště</city>
        <zip>686 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90045-001</name>
      <address>
        <city>Aalborg</city>
        <state>Nordjylland</state>
        <zip>9000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90045-004</name>
      <address>
        <city>Esbjerg</city>
        <zip>6700</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90045-003</name>
      <address>
        <city>Herning</city>
        <zip>7400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90045-006</name>
      <address>
        <city>Hvidovre</city>
        <zip>2650</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90045-002</name>
      <address>
        <city>Roskilde</city>
        <zip>4000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90045-005</name>
      <address>
        <city>Viborg</city>
        <zip>8800</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11049-006</name>
      <address>
        <city>Berlin</city>
        <zip>12627</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11049-002</name>
      <address>
        <city>Bochum</city>
        <zip>47787</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11049-003</name>
      <address>
        <city>Frankfurt</city>
        <zip>60313</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11049-001</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11049-007</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11036-001</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11036-004</name>
      <address>
        <city>Debrecen</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11036-002</name>
      <address>
        <city>Hatvan</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11036-003</name>
      <address>
        <city>Zalaegerszeg</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90031-001</name>
      <address>
        <city>Amersfoort</city>
        <zip>3813 TZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90031-003</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90031-006</name>
      <address>
        <city>Goes</city>
        <zip>4462 RA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90031-009</name>
      <address>
        <city>Hoorn</city>
        <zip>1624 NP</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90031-005</name>
      <address>
        <city>Utrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research SIte 11048-016</name>
      <address>
        <city>Brzozowie</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-018</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-079</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-011</name>
      <address>
        <city>Bydgoszcz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-004</name>
      <address>
        <city>Gdańsk</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-005</name>
      <address>
        <city>Gdynia</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-007</name>
      <address>
        <city>Katowice</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research SIte 11048-012</name>
      <address>
        <city>Katowice</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-003</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research SIte 11048-014</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-008</name>
      <address>
        <city>Lublin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-001</name>
      <address>
        <city>Poznań</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-019</name>
      <address>
        <city>Ruda Śląska</city>
        <zip>41-709</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research SIte 11048-013</name>
      <address>
        <city>Rzeszów</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research SIte 11048-015</name>
      <address>
        <city>Tarnów</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-006</name>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-009</name>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-002</name>
      <address>
        <city>Wrocław</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11048-010</name>
      <address>
        <city>Wrocław</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90027-008</name>
      <address>
        <city>Bellville</city>
        <state>Cape Town</state>
        <zip>7530</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90027-007</name>
      <address>
        <city>Lyttelton</city>
        <state>Cape Town</state>
        <zip>0157</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90027-003</name>
      <address>
        <city>Bloemfontein</city>
        <state>Free State</state>
        <zip>9301</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90027-010</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2193</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11027-005</name>
      <address>
        <city>Kempton Park</city>
        <state>Gauteng</state>
        <zip>1619</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90027-006</name>
      <address>
        <city>Pretoria</city>
        <state>Gauteng</state>
        <zip>0184</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90027-009</name>
      <address>
        <city>Witbank</city>
        <state>Gauteng</state>
        <zip>1035</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90027-001</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <zip>7500</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11027-007</name>
      <address>
        <city>Kuilsrivier</city>
        <state>Western Cape</state>
        <zip>7580</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11027-013</name>
      <address>
        <city>Paarl</city>
        <state>Western Cape</state>
        <zip>7646</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90027-004</name>
      <address>
        <city>Somerset West</city>
        <state>Western Cape</state>
        <zip>7130</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90027-005</name>
      <address>
        <city>Somerset West</city>
        <state>Western Cape</state>
        <zip>7130</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90034-004</name>
      <address>
        <city>Córdoba</city>
        <state>Andalucia</state>
        <zip>14004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90034-002</name>
      <address>
        <city>Zaragoza</city>
        <state>Aragon</state>
        <zip>5009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90034-005</name>
      <address>
        <city>Barcelona</city>
        <state>Cataluna</state>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90034-006</name>
      <address>
        <city>Barcelona</city>
        <state>Cataluna</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90034-001</name>
      <address>
        <city>Reus</city>
        <state>Cataluna</state>
        <zip>43204</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90034-003</name>
      <address>
        <city>La Coruña</city>
        <state>Galicia</state>
        <zip>15002</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90046-002</name>
      <address>
        <city>Göteborg</city>
        <zip>SE-41346</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90046-001</name>
      <address>
        <city>Stockholm</city>
        <zip>SE-11446</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 90046-003</name>
      <address>
        <city>Stockholm</city>
        <zip>SE-14186</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11380-005</name>
      <address>
        <city>Cherkasy</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11380-008</name>
      <address>
        <city>Kharkiv</city>
        <zip>61176</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11380-001</name>
      <address>
        <city>Kyiv</city>
        <zip>02002</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11380-002</name>
      <address>
        <city>Kyiv</city>
        <zip>03037</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11380-003</name>
      <address>
        <city>Kyiv</city>
        <zip>03049</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11380-004</name>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11380-009</name>
      <address>
        <city>Zaporizhzhya</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11380-006</name>
      <address>
        <city>Úzhgorod</city>
        <zip>88000</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-028</name>
      <address>
        <city>Bollington</city>
        <state>Cheshire</state>
        <zip>SK10 5JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-026</name>
      <address>
        <city>Bury</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-024</name>
      <address>
        <city>Cheadle Hulme</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-014</name>
      <address>
        <city>Chorley</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-012</name>
      <address>
        <city>Cornwell</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-010</name>
      <address>
        <city>Derby</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-006</name>
      <address>
        <city>Edgbaston</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-009</name>
      <address>
        <city>Exeter</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-001</name>
      <address>
        <city>Glasgow</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-008</name>
      <address>
        <city>Hexham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research SIte 11044-020</name>
      <address>
        <city>Macclesfield</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-005</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-025</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-027</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-029</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-019</name>
      <address>
        <city>Plymouth</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-003</name>
      <address>
        <city>Reading</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-022</name>
      <address>
        <city>Sale</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-023</name>
      <address>
        <city>Sale</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-002</name>
      <address>
        <city>Stockton-on-Tees</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-021</name>
      <address>
        <city>Timperley</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-007</name>
      <address>
        <city>Wales</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 11044-004</name>
      <address>
        <city>Waterloo</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Denmark</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>March 6, 2023</last_update_submitted>
  <last_update_submitted_qc>March 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Inclisiran sodium</keyword>
  <keyword>ASCVD</keyword>
  <keyword>LDL-C</keyword>
  <keyword>HeFH</keyword>
  <keyword>HoFH</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperlipoproteinemia Type II</mesh_term>
    <mesh_term>Homozygous Familial Hypercholesterolemia</mesh_term>
    <mesh_term>Hypercholesterolemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </patient_data>
  <!-- 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/NCT03814187
org study id: MDCO-PCS-17-05
secondary id: CKJX839A12306B
secondary id: 2017-003092-55
nct id: NCT03814187
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this extension study is to evaluate the efficacy, safety, and tolerability of
      long-term dosing of Inclisiran. The study will be a global multicenter study.
This study will be an open label, long term extension study in subjects with atherosclerotic
      cardiovascular disease (ASCVD), ASCVD-risk equivalents (eg, diabetes and familial
      hypercholesterolemia), or heterozygous or homozygous familial hypercholesterolemia (HeFH or
      HoFH) and elevated low density lipoprotein cholesterol (LDL-C) despite maximum tolerated dose
      of LDL-C lowering therapies who have completed the inclisiran Phase II trial MDCO-PCS-16-01
      (ORION-3), or any of the following Phase III lipid lowering studies: MDCO-PCS-17-03
      (ORION-9), MDCO-PCS-17-4 (ORION-10), or MDCO-PCS-17-08 (ORION-11)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of subjects achieving prespecified LDL-C targets.
time frame: Day 1080
description: A primary objective of the study is to evaluate the effect of inclisiran treatment on the proportion of subjects achieving prespecified LDL-C targets at end of study.
measure: Incidence of Adverse Events and Serious Adverse Events
time frame: Baseline, Day 1080
description: Safety assessments include adverse events and serious adverse events for long-term safety profile
measure: Absolute and percentage change in LDL-C from baseline.
time frame: Baseline, Day 1080
description: A secondary objective of this study is to evaluate the effect of inclisiran on LDL-C levels.
measure: Absolute and percentage change in other lipids and lipoprotein from baseline.
time frame: Baseline, Day 1080
description: A secondary objective of this study is to evaluate the effect of inclisiran on other lipids and lipoproteins.
arm group label: Inclisiran
arm group type: Experimental
description: Inclisiran sodium 300 milligrams (mg) will be administered as a single SC injection on Day 1*, 90, then every 180 days to Day 990.
*Subjects who received blinded placebo in the feeder study will receive blinded inclisiran and subjects who received blinded inclisiran in the feeder study will receive blinded placebo on Day 1 in ORION-8. Subjects from the open label ORION-3 study will not receive any injection of study drug on Day 1. Their first dose of study medication will be at day 90
intervention type: Drug
intervention name: Inclisiran Sodium
description: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
arm group label: Inclisiran
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Scott Wright, MD
role: Principal Investigator
affiliation: Mayo Clinic
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country: Canada
country: Czechia
country: Denmark
country: Germany
country: Hungary
country: Netherlands
country: Poland
country: South Africa
country: Spain
country: Sweden
country: Ukraine
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Hyperlipoproteinemia Type II
mesh term: Homozygous Familial Hypercholesterolemia
mesh term: Hypercholesterolemia
sharing ipd: Yes
ipd description: Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com