<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/NCT03811561</url>
  </required_header>
  <id_info>
    <org_study_id>NN9535-4352</org_study_id>
    <secondary_id>U1111-1201-6256</secondary_id>
    <secondary_id>2017-003619-20</secondary_id>
    <nct_id>NCT03811561</nct_id>
  </id_info>
  <brief_title>A Research Study to Look at How Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People With Type 2 Diabetes</brief_title>
  <acronym>FOCUS</acronym>
  <official_title>Long-term Effects of Semaglutide on Diabetic Retinopathy in Subjects With Type 2 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novo Nordisk A/S</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novo Nordisk A/S</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>
      This study will look at the long-term effects of semaglutide (active medicine) on diabetic&#xD;
      eye disease when compared to placebo (dummy medicine). The study will be performed in people&#xD;
      with type 2 diabetes. Participants will either get semaglutide or placebo in addition to&#xD;
      their diabetes medicines - which treatment the participant gets is decided by chance.&#xD;
      Participants will inject the study medicine using a pen-injector. The medicine must be&#xD;
      injected in a skin fold in the stomach, thigh or upper arm once a week. The study will last&#xD;
      for 5 years.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 8, 2019</start_date>
  <completion_date type="Anticipated">November 7, 2027</completion_date>
  <primary_completion_date type="Anticipated">December 25, 2026</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>
    <masking_description>Sponsor staff involved in the clinical trial is masked according to company standard procedures.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Presence of at least 3 steps Early Treatment Diabetic Retinopathy Study (ETDRS) subject level progression.</measure>
    <time_frame>Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time from randomisation to first at least 3 steps ETDRS subject level progression or central involved diabetic macular oedema (ciDME) in either eye.</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Measured in months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in visual acuity in the worse seeing eye.</measure>
    <time_frame>Week 0, Year 5</time_frame>
    <description>Measured in number of letters using the ETDRS protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in visual acuity in the better seeing eye.</measure>
    <time_frame>Week 0, Year 5</time_frame>
    <description>Measured in number of letters using the ETDRS protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with focal/grid laser photocoagulation.</measure>
    <time_frame>Week 0-Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with pan-retinal laser photocoagulation.</measure>
    <time_frame>Week 0-Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with anti-vascular endothelial growth factor (VEGF).</measure>
    <time_frame>Week 0-Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with steroid.</measure>
    <time_frame>Week 0-Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with vitrectomy.</measure>
    <time_frame>Week 0-Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of at least 3 steps ETDRS subject level improvement.</measure>
    <time_frame>Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of at least 2 steps ETDRS subject level progression.</measure>
    <time_frame>Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of at least 2 steps ETDRS subject level improvement.</measure>
    <time_frame>Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of persistent visual acuity up to 38 ETDRS letters in either eye.</measure>
    <time_frame>Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of persistent at least 2 lines (10 letters) ETDRS worsening in visual acuity in either eye from baseline.</measure>
    <time_frame>Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of persistent at least 3 lines (15 letters) ETDRS worsening in visual acuity in either eye from baseline.</measure>
    <time_frame>Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of persistent at least 2 lines (10 letters) ETDRS improvement in visual acuity in either eye from baseline.</measure>
    <time_frame>Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persistent at least 3 lines (15 letters) ETDRS improvement in visual acuity in either eye from baseline.</measure>
    <time_frame>Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of ciDME in either eye.</measure>
    <time_frame>Year 5</time_frame>
    <description>Percentage of subjects (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in glycosylated haemoglobin (HbA1c).</measure>
    <time_frame>Week 0, Year 5</time_frame>
    <description>Measured in %-points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in body weight.</measure>
    <time_frame>Week 0, Year 5</time_frame>
    <description>Measured in kg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in systolic and diastolic blood pressure.</measure>
    <time_frame>Week 0, Year 5</time_frame>
    <description>Measured in mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Lipids: Total-cholesterol, High density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides.</measure>
    <time_frame>Week 0, Year 5</time_frame>
    <description>Measured in mmol/L</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1500</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Semaglutide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive semaglutide once weekly as subcutaneous (s.c., under the skin) injection added to standard of care.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo (semaglutide) once weekly as subcutaneous subcutaneous (s.c., under the skin) injection added to standard of care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Semaglutide</intervention_name>
    <description>Participants will get one dose of semaglutide once weekly in addition to their diabetes medicines - which treatment they get is decided by chance. Participants will inject the study medicine using a pre-filled PDS290 pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. Participants will start with once-weekly doses of 0.25 mg for 4 weeks, then the dose will be gradually increased to 0.5 mg once weekly for 4 weeks, and finally to 1.0 mg once weekly (maximum dose) up to 260 weeks (5 years).</description>
    <arm_group_label>Semaglutide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (semaglutide)</intervention_name>
    <description>Participants will get one dose of placebo (semaglutide) once weekly in addition to their diabetes medicines - which treatment they get is decided by chance. Participants will inject the study medicine using a pre-filled PDS290 pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. Participants will start with once-weekly doses of 0.25 mg for 4 weeks, then the dose will be gradually increased to 0.5 mg once weekly for 4 weeks, and finally to 1.0 mg once weekly (maximum dose) up to 260 weeks (5 years).</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, age greater than or equal to 18 years at the time of signing informed&#xD;
             consent&#xD;
&#xD;
          -  Diagnosed with type 2 diabetes mellitus.&#xD;
&#xD;
          -  HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive).&#xD;
&#xD;
          -  Eye inclusion criteria (both eyes must meet all criteria):&#xD;
&#xD;
          -  Early Treatment Diabetic Retinopathy Study (ETDRS) level of 10-75 (both inclusive)&#xD;
             evaluated by fundus photography and confirmed by central reading centre&#xD;
&#xD;
          -  No ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema&#xD;
             six months prior to the day of screening.&#xD;
&#xD;
          -  No anticipated need for ocular or intraocular treatment for diabetic retinopathy or&#xD;
             diabetic macular oedema within three months after randomisation.&#xD;
&#xD;
          -  Best-corrected visual acuity greater than or equal to 30 letters using the ETDRS&#xD;
             visual acuity protocol&#xD;
&#xD;
          -  No previous treatment with pan-retinal laser photocoagulation&#xD;
&#xD;
          -  No substantial non-diabetic ocular condition that, in the opinion of the&#xD;
             ophthalmologist, would impact diabetic retinopathy or diabetic macular oedema&#xD;
             progression during the trial&#xD;
&#xD;
          -  No substantial media opacities that would preclude successful imaging&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any of the following: myocardial infarction, stroke, hospitalization for unstable&#xD;
             angina pectoris or transient ischaemic attack within the past 60 days prior to the day&#xD;
             of screening&#xD;
&#xD;
          -  Planned coronary, carotid or peripheral artery revascularisation known on the day of&#xD;
             screening&#xD;
&#xD;
          -  Subjects presently classified as being in New York Heart Association (NYHA) Class IV&#xD;
&#xD;
          -  Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR&#xD;
             less than 30 ml/min/1.73 m^2&#xD;
&#xD;
          -  Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or&#xD;
             medullary thyroid carcinoma&#xD;
&#xD;
          -  Presence or history of malignant neoplasms within the past 5 years prior to the day of&#xD;
             screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed&#xD;
&#xD;
          -  Female who is pregnant, breast-feeding or intends to become pregnant or is of&#xD;
             child-bearing potential and not using highly effective contraceptive methods&#xD;
&#xD;
          -  Concurrent treatment with any GLP-1 receptor agonist or DPP-4 inhibitor from&#xD;
             randomisation.&#xD;
&#xD;
          -  Receipt of any investigational medicinal product within 30 days before screening&#xD;
&#xD;
          -  Previous participation in this trial. Participation is defined as randomisation&#xD;
&#xD;
          -  Known or suspected hypersensitivity to trial products or related products&#xD;
&#xD;
          -  Any disorder, which in the investigator's opinion might jeopardise subject's safety or&#xD;
             compliance with the protocol&#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 Reporting Anchor and Disclosure (1452)</last_name>
    <role>Study Director</role>
    <affiliation>Novo Nordisk A/S</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85050</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85715</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Coronado</city>
        <state>California</state>
        <zip>92118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Costa Mesa</city>
        <state>California</state>
        <zip>92627</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Huntington Beach</city>
        <state>California</state>
        <zip>92648</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lomita</city>
        <state>California</state>
        <zip>90717</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Rancho Cucamonga</city>
        <state>California</state>
        <zip>91730-3063</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95821</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Ventura</city>
        <state>California</state>
        <zip>93003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Walnut Creek</city>
        <state>California</state>
        <zip>94598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Waterbury</city>
        <state>Connecticut</state>
        <zip>06708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33175</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Ocala</city>
        <state>Florida</state>
        <zip>34471</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30318</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Roswell</city>
        <state>Georgia</state>
        <zip>30076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Avon</city>
        <state>Indiana</state>
        <zip>46123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>West Des Moines</city>
        <state>Iowa</state>
        <zip>50265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Paducah</city>
        <state>Kentucky</state>
        <zip>42001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89148</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Nashua</city>
        <state>New Hampshire</state>
        <zip>03063</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Mentor</city>
        <state>Ohio</state>
        <zip>44060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bristol</city>
        <state>Tennessee</state>
        <zip>37620-7352</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37411</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kingsport</city>
        <state>Tennessee</state>
        <zip>37660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-9302</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Shavano Park</city>
        <state>Texas</state>
        <zip>78231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Sugar Land</city>
        <state>Texas</state>
        <zip>77478</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>São Paulo</city>
        <state>Sao Paulo</state>
        <zip>01228-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Pleven</city>
        <zip>5800</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Pleven</city>
        <zip>5806</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Plovdiv</city>
        <zip>4002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Plovdiv</city>
        <zip>4003</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Sofia</city>
        <zip>1233</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Sofia</city>
        <zip>1606</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Sofia</city>
        <zip>1618</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2E1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Concord</city>
        <state>Ontario</state>
        <zip>L4K 4M2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Etobicoke</city>
        <state>Ontario</state>
        <zip>M9R 4E1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4G 3E8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Saint-Laurent</city>
        <state>Quebec</state>
        <zip>H4T 1Z9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Brno</city>
        <zip>62500</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>500 05</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Praha 10</city>
        <zip>100 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Praha 4</city>
        <zip>140 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Praha</city>
        <zip>100 34</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Friedrichsthal</city>
        <zip>66299</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Hamburg</city>
        <zip>21109</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Hamburg</city>
        <zip>22607</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Münster</city>
        <zip>48145</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Münster</city>
        <zip>48153</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Rehlingen-Siersburg</city>
        <zip>66780</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Saint Ingbert-Oberwürzbach</city>
        <zip>66386</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Athens</city>
        <zip>115 25</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Athens</city>
        <zip>GR-11527</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Athens</city>
        <zip>GR-17562</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Haidari-Athens</city>
        <zip>GR-12462</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Thessaloniki</city>
        <zip>GR-54642</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Thessaloniki</city>
        <zip>GR-57001</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Guntur</city>
        <state>Andhra Pradesh</state>
        <zip>522001</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bangalore</city>
        <state>Karnataka</state>
        <zip>560 099</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bangalore</city>
        <state>Karnataka</state>
        <zip>560010</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kochi</city>
        <state>Kerala</state>
        <zip>682041</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Thiruvananthapuram</city>
        <state>Kerala</state>
        <zip>695031</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Mumbai</city>
        <state>Maharashtra</state>
        <zip>400008</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Nagpur</city>
        <state>Maharashtra</state>
        <zip>440003</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Pune</city>
        <state>Maharashtra</state>
        <zip>411004</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Ansari Nagar, New Delhi 110029</city>
        <state>New Delhi</state>
        <zip>110029</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Delhi</city>
        <state>New Delhi</state>
        <zip>110076</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Ludhiana</city>
        <state>Punjab</state>
        <zip>141008</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Chennai</city>
        <state>Tamil Nadu</state>
        <zip>600086</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Madurai</city>
        <state>Tamil Nadu</state>
        <zip>625 020</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kolkata</city>
        <state>West Bengal</state>
        <zip>700020</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kolkata</city>
        <state>West Bengal</state>
        <zip>700054</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Hyderabad</city>
        <zip>600034</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Haifa</city>
        <zip>31096</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Jerusalem</city>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kfar Saba</city>
        <zip>44281</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Petah-Tikva</city>
        <zip>49100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tel Hashomer</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Tel-Aviv</city>
        <zip>64239</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Jelgava</city>
        <zip>LV-3001</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Ogre</city>
        <zip>LV-5001</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Riga</city>
        <zip>LV-1002</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Riga</city>
        <zip>LV-1011</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Riga</city>
        <zip>LV-1024</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Distrito Federal</city>
        <state>México, D.F.</state>
        <zip>14080</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Monterrey</city>
        <state>Nuevo León</state>
        <zip>64460</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bialystok</city>
        <state>Podlaskie Voivodeship</state>
        <zip>15-276</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-048</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Chorzow</city>
        <zip>41-500</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Gdansk</city>
        <zip>80-382</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Gdansk</city>
        <zip>80-858</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Katowice</city>
        <zip>40-081</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Krakow</city>
        <zip>31-501</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lodz</city>
        <zip>90-302</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lodz</city>
        <zip>94-074 LODZ</zip>
        <country>Poland</country>
      </address>
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        <zip>09-100</zip>
        <country>Poland</country>
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    <facility>
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        <zip>60-821</zip>
        <country>Poland</country>
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      <address>
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        <zip>61-251</zip>
        <country>Poland</country>
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    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Zabrze</city>
        <zip>41-800</zip>
        <country>Poland</country>
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  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Almada</city>
        <zip>2805-267</zip>
        <country>Portugal</country>
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  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Aveiro</city>
        <zip>3814-501</zip>
        <country>Portugal</country>
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  </location>
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    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Coimbra</city>
        <zip>3000-459</zip>
        <country>Portugal</country>
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    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Guimarães</city>
        <zip>4835-044</zip>
        <country>Portugal</country>
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    </facility>
  </location>
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    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Lisboa</city>
        <zip>1250-230</zip>
        <country>Portugal</country>
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    </facility>
  </location>
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    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Matosinhos</city>
        <zip>4464-513</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Porto</city>
        <zip>4200-319</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Setubal</city>
        <zip>2910-446</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
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    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Cluj Napoca</city>
        <state>Cluj</state>
        <zip>400006</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Timisoara</city>
        <state>Timis</state>
        <zip>300456</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Timisoara</city>
        <state>Timis</state>
        <zip>300736</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bucharest</city>
        <zip>010825</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bucharest</city>
        <zip>011025</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bucharest</city>
        <zip>020359</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
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    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bucharest</city>
        <zip>020475</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Barnaul</city>
        <zip>656043</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kazan</city>
        <zip>420012</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Kazan</city>
        <zip>420061</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Moscow</city>
        <zip>117292</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
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    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630087</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
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    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Saint-Peterburg</city>
        <zip>194044</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>194354</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
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    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>196084</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197110</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Saratov</city>
        <zip>410031</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Saratov</city>
        <zip>410039</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Novi Sad</city>
        <state>Vojvodina</state>
        <zip>21000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Belgrade</city>
        <zip>11080</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Nis</city>
        <zip>18000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bratislava</city>
        <zip>82606</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Bratislava</city>
        <zip>833 05</zip>
        <country>Slovakia</country>
      </address>
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  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Zilina</city>
        <zip>01001</zip>
        <country>Slovakia</country>
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  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
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  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Hospitalet de Llobregat</city>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>La Coruña</city>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Pamplona</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Nottingham</city>
        <state>Nottinghamshire</state>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>London</city>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Norfolk</city>
        <zip>NR4 7UQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>North Yorkshire</city>
        <zip>HG2 7SX</zip>
        <country>United Kingdom</country>
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  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Nuneaton</city>
        <zip>CV10 7DJ</zip>
        <country>United Kingdom</country>
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    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Somerset</city>
        <zip>BA21 4AT</zip>
        <country>United Kingdom</country>
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    </facility>
  </location>
  <location>
    <facility>
      <name>Novo Nordisk Investigational Site</name>
      <address>
        <city>Truro</city>
        <zip>TR1 3LJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>India</country>
    <country>Israel</country>
    <country>Latvia</country>
    <country>Mexico</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>Slovakia</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>August 21, 2023</last_update_submitted>
  <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2023</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>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>According to the Novo Nordisk disclosure commitment on novonordisk-trials.com</ipd_description>
    <ipd_url>http://novonordisk-trials.com</ipd_url>
  </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/NCT03811561
org study id: NN9535-4352
secondary id: U1111-1201-6256
secondary id: 2017-003619-20
nct id: NCT03811561
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will look at the long-term effects of semaglutide (active medicine) on diabetic
      eye disease when compared to placebo (dummy medicine). The study will be performed in people
      with type 2 diabetes. Participants will either get semaglutide or placebo in addition to
      their diabetes medicines - which treatment the participant gets is decided by chance.
      Participants will inject the study medicine using a pen-injector. The medicine must be
      injected in a skin fold in the stomach, thigh or upper arm once a week. The study will last
      for 5 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Sponsor staff involved in the clinical trial is masked according to company standard procedures.
measure: Presence of at least 3 steps Early Treatment Diabetic Retinopathy Study (ETDRS) subject level progression.
time frame: Year 5
description: Percentage of subjects (yes/no).
measure: Time from randomisation to first at least 3 steps ETDRS subject level progression or central involved diabetic macular oedema (ciDME) in either eye.
time frame: Up to 5 years
description: Measured in months.
measure: Change in visual acuity in the worse seeing eye.
time frame: Week 0, Year 5
description: Measured in number of letters using the ETDRS protocol.
measure: Change in visual acuity in the better seeing eye.
time frame: Week 0, Year 5
description: Measured in number of letters using the ETDRS protocol.
measure: Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with focal/grid laser photocoagulation.
time frame: Week 0-Year 5
description: Percentage of subjects (yes/no).
measure: Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with pan-retinal laser photocoagulation.
time frame: Week 0-Year 5
description: Percentage of subjects (yes/no).
measure: Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with anti-vascular endothelial growth factor (VEGF).
time frame: Week 0-Year 5
description: Percentage of subjects (yes/no).
measure: Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with steroid.
time frame: Week 0-Year 5
description: Percentage of subjects (yes/no).
measure: Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with vitrectomy.
time frame: Week 0-Year 5
description: Percentage of subjects (yes/no).
measure: Presence of at least 3 steps ETDRS subject level improvement.
time frame: Year 5
description: Percentage of subjects (yes/no).
measure: Presence of at least 2 steps ETDRS subject level progression.
time frame: Year 5
description: Percentage of subjects (yes/no).
measure: Presence of at least 2 steps ETDRS subject level improvement.
time frame: Year 5
description: Percentage of subjects (yes/no).
measure: Presence of persistent visual acuity up to 38 ETDRS letters in either eye.
time frame: Year 5
description: Percentage of subjects (yes/no).
measure: Presence of persistent at least 2 lines (10 letters) ETDRS worsening in visual acuity in either eye from baseline.
time frame: Year 5
description: Percentage of subjects (yes/no).
measure: Presence of persistent at least 3 lines (15 letters) ETDRS worsening in visual acuity in either eye from baseline.
time frame: Year 5
description: Percentage of subjects (yes/no).
measure: Presence of persistent at least 2 lines (10 letters) ETDRS improvement in visual acuity in either eye from baseline.
time frame: Year 5
description: Percentage of subjects (yes/no).
measure: Persistent at least 3 lines (15 letters) ETDRS improvement in visual acuity in either eye from baseline.
time frame: Year 5
description: Percentage of subjects (yes/no).
measure: Presence of ciDME in either eye.
time frame: Year 5
description: Percentage of subjects (yes/no).
measure: Change in glycosylated haemoglobin (HbA1c).
time frame: Week 0, Year 5
description: Measured in %-points.
measure: Change in body weight.
time frame: Week 0, Year 5
description: Measured in kg.
measure: Change in systolic and diastolic blood pressure.
time frame: Week 0, Year 5
description: Measured in mmHg.
measure: Change in Lipids: Total-cholesterol, High density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides.
time frame: Week 0, Year 5
description: Measured in mmol/L
arm group label: Semaglutide
arm group type: Experimental
description: Participants will receive semaglutide once weekly as subcutaneous (s.c., under the skin) injection added to standard of care.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive placebo (semaglutide) once weekly as subcutaneous subcutaneous (s.c., under the skin) injection added to standard of care.
intervention type: Drug
intervention name: Semaglutide
description: Participants will get one dose of semaglutide once weekly in addition to their diabetes medicines - which treatment they get is decided by chance. Participants will inject the study medicine using a pre-filled PDS290 pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. Participants will start with once-weekly doses of 0.25 mg for 4 weeks, then the dose will be gradually increased to 0.5 mg once weekly for 4 weeks, and finally to 1.0 mg once weekly (maximum dose) up to 260 weeks (5 years).
arm group label: Semaglutide
intervention type: Drug
intervention name: Placebo (semaglutide)
description: Participants will get one dose of placebo (semaglutide) once weekly in addition to their diabetes medicines - which treatment they get is decided by chance. Participants will inject the study medicine using a pre-filled PDS290 pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. Participants will start with once-weekly doses of 0.25 mg for 4 weeks, then the dose will be gradually increased to 0.5 mg once weekly for 4 weeks, and finally to 1.0 mg once weekly (maximum dose) up to 260 weeks (5 years).
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Reporting Anchor and Disclosure (1452)
role: Study Director
affiliation: Novo Nordisk A/S
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country: Brazil
country: Bulgaria
country: Canada
country: Czechia
country: Germany
country: Greece
country: India
country: Israel
country: Latvia
country: Mexico
country: Poland
country: Portugal
country: Romania
country: Russian Federation
country: Serbia
country: Slovakia
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
sharing ipd: Yes
ipd description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
ipd url: http://novonordisk-trials.com