<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/NCT03762850</url>
  </required_header>
  <id_info>
    <org_study_id>021IGAN17001</org_study_id>
    <secondary_id>2017-004605-41</secondary_id>
    <nct_id>NCT03762850</nct_id>
  </id_info>
  <brief_title>A Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy</brief_title>
  <acronym>PROTECT</acronym>
  <official_title>A Randomized, Multicenter, Double-blind, Parallel-group, Active-control Study of the Efficacy and Safety of Sparsentan for the Treatment of Immunoglobulin A Nephropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Travere Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Travere Therapeutics, Inc.</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>
      To determine the long-term (approximately 2 years) nephroprotective potential of treatment&#xD;
      with sparsentan as compared to an angiotensin receptor blocker in patients with&#xD;
      immunoglobulin A nephropathy (IgAN).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 114-week,randomized, multicenter, double-blind, parallel-group, active-control&#xD;
      study with an open-label extension period of up to 156 weeks, for a total duration of up to&#xD;
      270 weeks in patients with IgAN who have persistent overt proteinuria and remain at high risk&#xD;
      of disease progression despite being on a stable dose (or doses) of an angiotensin-converting&#xD;
      enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) that is (are) a maximum&#xD;
      tolerated dose that is at least one half of the maximum labeled dose (MLD) (according to&#xD;
      approved labeling. Approximately 380 patients aged ≥18 years will be enrolled in the study&#xD;
      globally. The investigational drug (sparsentan) is a dual acting angiotensin receptor blocker&#xD;
      and endothelin receptor antagonist. The active control is irbesartan.&#xD;
&#xD;
      The purpose of the study is to evaluate the potential benefit of sparsentan on kidney&#xD;
      function by analyzing change in proteinuria (protein in urine) and estimated glomerular&#xD;
      filtration rate (eGFR) as compared to current standard treatment.&#xD;
&#xD;
      Patients enrolled in the PROTECT study (Protocol 021IGAN17001) will be those at high risk of&#xD;
      progressing to renal failure. They will be randomly assigned in a 1:1 ratio to either&#xD;
      sparsentan or irbesartan, as the active control (current standard treatment) at the Day 1&#xD;
      (Randomization) visit. Study medication (sparsentan and irbesartan) will be administered as a&#xD;
      single oral morning dose.&#xD;
&#xD;
      The primary analysis is change in proteinuria (urine protein/creatinine ratio) from baseline&#xD;
      at Week 36 in sparsentan-treated patients as compared to irbesartan-treated patients.&#xD;
&#xD;
      Primary completion date represents the anticipated completion date of the double-blind&#xD;
      portion of the study. Study completion date represents the anticipated completion date of the&#xD;
      open-label extension portion of the study.&#xD;
&#xD;
      Patients participating in the open-label extension period may be evaluated for eligibility to&#xD;
      participate in a randomized, open-label, controlled Sub study evaluating the safety and&#xD;
      efficacy of an SGLT2 inhibitor in addition to stable sparsentan treatment (OLE Sub study).&#xD;
      The SGLT2 inhibitor, dapagliflozin will be provided as &quot;study medication&quot; for the OLE Sub&#xD;
      study. Following completion of the visit 12 weeks after the OLE baseline visit, eligible&#xD;
      patients may receive open-label dapagliflozin for at least 12 weeks but up to 24 additional&#xD;
      weeks, or through the end of the open-label extension period, whichever is shortest.&#xD;
      Approximately 60 patients from the open-label extension period will be enrolled into the OLE&#xD;
      Sub study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 11, 2018</start_date>
  <completion_date type="Anticipated">July 2026</completion_date>
  <primary_completion_date type="Actual">August 7, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Urine protein/creatinine ratio (UP/C) at Week 36</measure>
    <time_frame>After the last patient randomized has undergone the Week 36 visit</time_frame>
    <description>The primary efficacy endpoint is the change from baseline (Day 1) in the UP/C based on a 24-hour urine sample at Week 36.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>eGFR over a 52-week period</measure>
    <time_frame>Week 58 postrandomization</time_frame>
    <description>The rate of change in estimated glomerular filtration rate (eGFR) over a 52-week period following the initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks postrandomization to 58 weeks postrandomization eGFR chronic slope at 1 year.)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>eGFR over a 104-week period</measure>
    <time_frame>Week 110 postrandomization</time_frame>
    <description>The rate of change in estimated glomerular filtration rate (eGFR) over a 104-week period following initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks postrandomization to 110 weeks postrandomization eGFR chronic slope at 2 years.)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>eGFR over a 110-week period</measure>
    <time_frame>Week 110 postrandomization</time_frame>
    <description>The rate of change in eGFR over a 110-week (approximately 2 years) period following the initiation of randomized therapy (thus, the analysis is from Day 1 to 110 weeks postrandomization eGFR total slope at 2 years).</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">380</enrollment>
  <condition>Immunoglobulin A Nephropathy</condition>
  <arm_group>
    <arm_group_label>sparsentan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Double-blind: Sparsentan will be administered daily as a 200-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 200 mg after 2 weeks will increase their dose to 400- mg and continue treatment to Week 110.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>irbesartan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Double-blind: Irbesartan will be administered daily as a 150-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 150 mg after 2 weeks will increase their dose to 300 mg and continue treatment to Week 110.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dapagliflozin + sparsentan (Sub study)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OLE Sub study: Dapagliflozin will be administered daily as a 5-mg oral tablet, in addition to 400-mg of Sparsentan, for a period of 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sparsentan (Sub Study)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sparsentan</intervention_name>
    <description>Target dose of 400 mg daily</description>
    <arm_group_label>dapagliflozin + sparsentan (Sub study)</arm_group_label>
    <arm_group_label>sparsentan</arm_group_label>
    <arm_group_label>sparsentan (Sub Study)</arm_group_label>
    <other_name>RE-021</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>irbesartan</intervention_name>
    <description>Target dose of 300 mg daily</description>
    <arm_group_label>irbesartan</arm_group_label>
    <other_name>Irbesartan Tablets USP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <description>Target dose of 10 mg daily</description>
    <arm_group_label>dapagliflozin + sparsentan (Sub study)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria for the Double-Blind Period:&#xD;
&#xD;
          -  Age 18 years or older at screening&#xD;
&#xD;
          -  Biopsy-proven primary IgAN&#xD;
&#xD;
          -  Proteinuria of ≥1 g/day at screening&#xD;
&#xD;
          -  eGFR ≥30 mL/min/1.73 m2 at screening&#xD;
&#xD;
          -  Currently on stable dose of ACEI and/or ARB therapy, for at least 12 weeks prior to&#xD;
             screening (maximum tolerated dose and at least one-half of the maximum labeled dose)&#xD;
&#xD;
          -  Systolic BP ≤150 mmHg and diastolic BP ≤100 mmHg at screening&#xD;
&#xD;
          -  Willing to undergo change in ACEI and/or ARB and anti-hypertensive medications&#xD;
&#xD;
          -  Agree to contraception&#xD;
&#xD;
        Key Exclusion Criteria for the Double-Blind Period:&#xD;
&#xD;
          -  IgAN secondary to another condition&#xD;
&#xD;
          -  Presence of cellular glomerular crescents in &gt;25% of glomeruli on renal biopsy (if&#xD;
             biopsy available within 6 months of screening)&#xD;
&#xD;
          -  Chronic kidney disease (CKD) in addition to IgAN&#xD;
&#xD;
          -  History of organ transplantation, with exception of corneal transplants&#xD;
&#xD;
          -  Require any prohibited medications&#xD;
&#xD;
          -  Treatment of systemic immunosuppressive medications (including corticosteroids) for &gt;2&#xD;
             weeks within 3 months of screening&#xD;
&#xD;
          -  History of heart failure or previous hospitalization for heart failure or unexplained&#xD;
             dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema&#xD;
&#xD;
          -  Clinically significant cerebrovascular disease or coronary artery disease within 6&#xD;
             months of screening&#xD;
&#xD;
          -  Jaundice, hepatitis, or known hepatobiliary disease or elevations of transaminases&#xD;
             (ALT/AST) &gt;2 times upper limit of normal at screening&#xD;
&#xD;
          -  History of malignancy other than adequately treated basal cell or squamous cell skin&#xD;
             cancer or cervical carcinoma within the past 2 years&#xD;
&#xD;
          -  Hematocrit value &lt;27% (0.27 V/V) or hemoglobin value &lt;9 g/dL (90 g/L) at Screening&#xD;
&#xD;
          -  Potassium &gt;5.5 mEq/L (5.5 mmol/L) at Screening&#xD;
&#xD;
          -  History of alcohol of illicit drug use disorder&#xD;
&#xD;
          -  History of serious side effect or allergic response to any angiotensin II antagonist&#xD;
             or endothelin receptor antagonist, including sparsentan or irbesartan, or has a&#xD;
             hypersensitivity to any of the excipients in the study medications&#xD;
&#xD;
          -  For female: Pregnancy, or planning to become pregnant during the course of the study,&#xD;
             or breastfeeding&#xD;
&#xD;
          -  Participation in a study of another investigational product within 28 days of&#xD;
             screening&#xD;
&#xD;
        Key Inclusion Criteria for the Open-Label Extension Period based on assessments at the Week&#xD;
        110 visit:&#xD;
&#xD;
          -  Completed participation in the double-blind period, including the Week 114 visit&#xD;
&#xD;
          -  Did not permanently discontinue study medication during the double-blind period&#xD;
&#xD;
          -  Agree to contraception&#xD;
&#xD;
        Key Exclusion Criteria for the Open-Label Extension Period based on assessments at the Week&#xD;
        110 and Week 114 visits:&#xD;
&#xD;
          -  Progression to end-stage renal disease (ESRD) requiring renal replacement therapy&#xD;
             (RRT)&#xD;
&#xD;
          -  Development of any criteria for discontinuation of study medication or discontinuation&#xD;
             from the study, between Week 110 and Week 114&#xD;
&#xD;
          -  Patient was unable to initiate, or developed contraindications to, treatment with RAAS&#xD;
             inhibitors between Week 110 and Week 114&#xD;
&#xD;
          -  eGFR ≤20 mL/min/1.73 m2 at Week 110&#xD;
&#xD;
          -  Female patient is pregnant or breastfeeding&#xD;
&#xD;
        Key Inclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:&#xD;
&#xD;
          -  Participating in the open-label extension and is willing and able to provide signed&#xD;
             informed consent for participation in the open-label extension period Sub study&#xD;
&#xD;
          -  A urine protein excretion value of ≥0.3 g/day.&#xD;
&#xD;
          -  An eGFR of ≥25 mL/min/1.73m2&#xD;
&#xD;
          -  On a stable dose of sparsentan for ≥8 weeks in the open-label extension period that is&#xD;
             the maximum tolerated dose.&#xD;
&#xD;
        Key Exclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:&#xD;
&#xD;
          -  Progressed to ESRD requiring RRT&#xD;
&#xD;
          -  Initiated or changed dose of a systemic immunosuppressive medication (including&#xD;
             systemic steroids) within 12 weeks&#xD;
&#xD;
          -  Taking an SGLT2 inhibitor within 12 weeks&#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>Priscila Preciado, MD</last_name>
    <role>Study Director</role>
    <affiliation>Travere Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Homewood</city>
        <state>Alabama</state>
        <zip>35209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Montebello</city>
        <state>California</state>
        <zip>90640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Northridge</city>
        <state>California</state>
        <zip>91324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103-6204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Coral Springs</city>
        <state>Florida</state>
        <zip>33071</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33186</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Winter Park</city>
        <state>Florida</state>
        <zip>32789</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Lawrenceville</city>
        <state>Georgia</state>
        <zip>30046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Nampa</city>
        <state>Idaho</state>
        <zip>83687</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Hinsdale</city>
        <state>Illinois</state>
        <zip>60521</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Muncie</city>
        <state>Indiana</state>
        <zip>47303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Springfield</city>
        <state>Massachusetts</state>
        <zip>01104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Reno</city>
        <state>Nevada</state>
        <zip>89511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Fresh Meadows</city>
        <state>New York</state>
        <zip>11365</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>El Paso</city>
        <state>Texas</state>
        <zip>79935</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Lewisville</city>
        <state>Texas</state>
        <zip>75057</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Marshfield</city>
        <state>Wisconsin</state>
        <zip>54449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Concord</city>
        <state>New South Wales</state>
        <zip>2139</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Gosford</city>
        <state>New South Wales</state>
        <zip>2250</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kingswood</city>
        <state>New South Wales</state>
        <zip>2747</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>New Lambton Heights</city>
        <state>New South Wales</state>
        <zip>2305</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Randwick</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>St Leonards</city>
        <state>New South Wales</state>
        <zip>2065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Birtinya</city>
        <state>Queensland</state>
        <zip>4575</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Reservoir</city>
        <state>Victoria</state>
        <zip>3073</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Bonheiden</city>
        <zip>2820</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Brugge</city>
        <zip>8310</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kortrijk</city>
        <zip>8500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Roeselare</city>
        <zip>8800</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Osijek</city>
        <zip>31000</zip>
        <country>Croatia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Zagreb</city>
        <zip>10000</zip>
        <country>Croatia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Praha 10</city>
        <zip>10034</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Praha 2</city>
        <zip>12808</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Tallinn</city>
        <zip>10617</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Tallinn</city>
        <zip>13419</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Tartu</city>
        <zip>50406</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Marseille</city>
        <state>Bouches-du-Rhone</state>
        <zip>13005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Montpellier Cedex 5</city>
        <state>Herault</state>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Grenoble Cedex 9</city>
        <state>Isere</state>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Saint-Priest-en-Jarez</city>
        <state>Loire</state>
        <zip>42270</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Paris Cedex 15</city>
        <state>Paris</state>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Clermont Ferrand Cedex</city>
        <state>Puy De Dome</state>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Créteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Villingen-Schwenningen</city>
        <state>Baden Wuerttemberg</state>
        <zip>78052</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Hanover</city>
        <state>Lower Saxony</state>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Duesseldorf</city>
        <state>Nordrhein Westfalen</state>
        <zip>40210</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Aachen</city>
        <state>North Rhine Westphalia</state>
        <zip>52074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kaiserslautern</city>
        <state>Rheinland Palatinate</state>
        <zip>67655</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Trier</city>
        <state>Rheinland Palatinate</state>
        <zip>54292</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kiel</city>
        <state>Schleswig Holstein</state>
        <zip>23538</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kiel</city>
        <state>Schleswig-Holstein</state>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Jena</city>
        <state>Thueringen</state>
        <zip>07747</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kwun Tong</city>
        <state>Kowloon</state>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Lai Chi Kok</city>
        <state>Kowloon</state>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Shatin</city>
        <state>New Territories</state>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Tsuen Wan</city>
        <state>New Territories</state>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Ranica</city>
        <state>Bergamo</state>
        <zip>24020</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Milan</city>
        <state>Lombardia</state>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Bari</city>
        <zip>70124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Catania</city>
        <zip>95123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Catanzaro</city>
        <zip>88100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Lecco</city>
        <zip>23900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Modena</city>
        <zip>41124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Seongnam-si</city>
        <state>Gyeonggi-do</state>
        <zip>13620</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Anyang-Si</city>
        <zip>14068</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Busan</city>
        <zip>47392</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Incheon</city>
        <zip>21565</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Seoul</city>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Seoul</city>
        <zip>06273</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Seoul</city>
        <zip>110-746</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Seoul</city>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kaunas</city>
        <zip>LT-50009</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Vilnius</city>
        <zip>LT-08661</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Grafton</city>
        <state>Auckland</state>
        <zip>1142</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Hamilton</city>
        <zip>3200</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Hastings</city>
        <zip>4120</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>New Plymouth</city>
        <zip>4342</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kraków</city>
        <zip>31-559</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Olsztyn</city>
        <zip>10-124</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Olsztyn</city>
        <zip>10-561</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Warszawa</city>
        <zip>04-749</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Wrocław</city>
        <zip>50-566</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Łódź</city>
        <zip>93-347</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Coimbra</city>
        <zip>3000-075</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Lisboa</city>
        <zip>1069-166</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Lisboa</city>
        <zip>1649-035</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Loures</city>
        <zip>2674-514</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Setúbal</city>
        <zip>2910-446</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Vila Nova De Gaia</city>
        <zip>4434-502</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Palma De Mallorca</city>
        <state>Baleares</state>
        <zip>07120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Sagunto</city>
        <state>Valencia</state>
        <zip>46520</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Valencia</city>
        <zip>46014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Valencia</city>
        <zip>46017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Hualien City</city>
        <zip>970</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Kaohsiung</city>
        <zip>81362</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>New Taipei City</city>
        <zip>220</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Taichung</city>
        <zip>40705</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Reading</city>
        <state>Berkshire</state>
        <zip>RG1 5AN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Middlesbrough</city>
        <state>Cleveland</state>
        <zip>TS4 3BW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Derby</city>
        <state>Derbyshire</state>
        <zip>DE22 3DT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Brighton</city>
        <state>East Sussex</state>
        <zip>BN2 5BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>E1 4AT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Manchester</city>
        <state>Greater Manchester</state>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Salford</city>
        <state>Greater Manchester</state>
        <zip>M6 8HD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Preston</city>
        <state>Lancashire</state>
        <zip>PR2 9HT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Leicester</city>
        <state>Leicestershire</state>
        <zip>LE5 4PW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Edinburgh</city>
        <state>Scotland</state>
        <zip>EH16 4SA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Stoke-on-Trent</city>
        <state>Staffordshire</state>
        <zip>ST4 6QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Glasgow</city>
        <state>Strathclyde</state>
        <zip>G11 6NT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Carshalton</city>
        <state>Surrey</state>
        <zip>SM5 1AA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Cardiff</city>
        <state>West Glamorgan</state>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B9 5SS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>Liverpool</city>
        <zip>L9 7AL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>London</city>
        <zip>E1 1FR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Travere Investigational Site</name>
      <address>
        <city>London</city>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Croatia</country>
    <country>Czechia</country>
    <country>Estonia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hong Kong</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Lithuania</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://travere.com</url>
    <description>Sponsor Website</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>September 1, 2023</last_update_submitted>
  <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 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>Kidney Diseases</mesh_term>
    <mesh_term>Glomerulonephritis, IGA</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dapagliflozin</mesh_term>
    <mesh_term>Irbesartan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03762850
org study id: 021IGAN17001
secondary id: 2017-004605-41
nct id: NCT03762850
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
To determine the long-term (approximately 2 years) nephroprotective potential of treatment
      with sparsentan as compared to an angiotensin receptor blocker in patients with
      immunoglobulin A nephropathy (IgAN).
This is a 114-week,randomized, multicenter, double-blind, parallel-group, active-control
      study with an open-label extension period of up to 156 weeks, for a total duration of up to
      270 weeks in patients with IgAN who have persistent overt proteinuria and remain at high risk
      of disease progression despite being on a stable dose (or doses) of an angiotensin-converting
      enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) that is (are) a maximum
      tolerated dose that is at least one half of the maximum labeled dose (MLD) (according to
      approved labeling. Approximately 380 patients aged ≥18 years will be enrolled in the study
      globally. The investigational drug (sparsentan) is a dual acting angiotensin receptor blocker
      and endothelin receptor antagonist. The active control is irbesartan.

      The purpose of the study is to evaluate the potential benefit of sparsentan on kidney
      function by analyzing change in proteinuria (protein in urine) and estimated glomerular
      filtration rate (eGFR) as compared to current standard treatment.

      Patients enrolled in the PROTECT study (Protocol 021IGAN17001) will be those at high risk of
      progressing to renal failure. They will be randomly assigned in a 1:1 ratio to either
      sparsentan or irbesartan, as the active control (current standard treatment) at the Day 1
      (Randomization) visit. Study medication (sparsentan and irbesartan) will be administered as a
      single oral morning dose.

      The primary analysis is change in proteinuria (urine protein/creatinine ratio) from baseline
      at Week 36 in sparsentan-treated patients as compared to irbesartan-treated patients.

      Primary completion date represents the anticipated completion date of the double-blind
      portion of the study. Study completion date represents the anticipated completion date of the
      open-label extension portion of the study.

      Patients participating in the open-label extension period may be evaluated for eligibility to
      participate in a randomized, open-label, controlled Sub study evaluating the safety and
      efficacy of an SGLT2 inhibitor in addition to stable sparsentan treatment (OLE Sub study).
      The SGLT2 inhibitor, dapagliflozin will be provided as "study medication" for the OLE Sub
      study. Following completion of the visit 12 weeks after the OLE baseline visit, eligible
      patients may receive open-label dapagliflozin for at least 12 weeks but up to 24 additional
      weeks, or through the end of the open-label extension period, whichever is shortest.
      Approximately 60 patients from the open-label extension period will be enrolled into the OLE
      Sub study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Urine protein/creatinine ratio (UP/C) at Week 36
time frame: After the last patient randomized has undergone the Week 36 visit
description: The primary efficacy endpoint is the change from baseline (Day 1) in the UP/C based on a 24-hour urine sample at Week 36.
measure: eGFR over a 52-week period
time frame: Week 58 postrandomization
description: The rate of change in estimated glomerular filtration rate (eGFR) over a 52-week period following the initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks postrandomization to 58 weeks postrandomization eGFR chronic slope at 1 year.)
measure: eGFR over a 104-week period
time frame: Week 110 postrandomization
description: The rate of change in estimated glomerular filtration rate (eGFR) over a 104-week period following initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks postrandomization to 110 weeks postrandomization eGFR chronic slope at 2 years.)
measure: eGFR over a 110-week period
time frame: Week 110 postrandomization
description: The rate of change in eGFR over a 110-week (approximately 2 years) period following the initiation of randomized therapy (thus, the analysis is from Day 1 to 110 weeks postrandomization eGFR total slope at 2 years).
arm group label: sparsentan
arm group type: Experimental
description: Double-blind: Sparsentan will be administered daily as a 200-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 200 mg after 2 weeks will increase their dose to 400- mg and continue treatment to Week 110.
arm group label: irbesartan
arm group type: Active Comparator
description: Double-blind: Irbesartan will be administered daily as a 150-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 150 mg after 2 weeks will increase their dose to 300 mg and continue treatment to Week 110.
arm group label: dapagliflozin + sparsentan (Sub study)
arm group type: Experimental
description: OLE Sub study: Dapagliflozin will be administered daily as a 5-mg oral tablet, in addition to 400-mg of Sparsentan, for a period of 12 weeks.
arm group label: sparsentan (Sub Study)
arm group type: Experimental
description: OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.
intervention type: Drug
intervention name: sparsentan
description: Target dose of 400 mg daily
arm group label: dapagliflozin + sparsentan (Sub study)
arm group label: sparsentan
arm group label: sparsentan (Sub Study)
other name: RE-021
intervention type: Drug
intervention name: irbesartan
description: Target dose of 300 mg daily
arm group label: irbesartan
other name: Irbesartan Tablets USP
intervention type: Drug
intervention name: Dapagliflozin
description: Target dose of 10 mg daily
arm group label: dapagliflozin + sparsentan (Sub study)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Priscila Preciado, MD
role: Study Director
affiliation: Travere Therapeutics, Inc.
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country: Australia
country: Belgium
country: Croatia
country: Czechia
country: Estonia
country: France
country: Germany
country: Hong Kong
country: Italy
country: Korea, Republic of
country: Lithuania
country: New Zealand
country: Poland
country: Portugal
country: Spain
country: Taiwan
country: United Kingdom
country: United States
url: http://travere.com
description: Sponsor Website
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Glomerulonephritis, IGA
mesh term: Dapagliflozin
mesh term: Irbesartan
sharing ipd: No