<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/NCT03013751</url>
  </required_header>
  <id_info>
    <org_study_id>PHN-Udenafil-03</org_study_id>
    <secondary_id>U01HL068270</secondary_id>
    <nct_id>NCT03013751</nct_id>
  </id_info>
  <brief_title>A Extension Study of Udenafil in Adolescents</brief_title>
  <acronym>FUELExten</acronym>
  <official_title>A Phase III Extension Study of Udenafil in Adolescents With Single Ventricle Physiology After Fontan Palliation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mezzion Pharma Co. Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mezzion Pharma Co. Ltd</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a 12-month (52 week) safety extension study to supplement the FUEL Phase III&#xD;
      clinical trial to provide safety information regarding the long-term use of udenafil in&#xD;
      adolescents with single ventricle congenital heart disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be an open-label extension study. All enrolled subjects will be provided with&#xD;
      udenafil for the duration of the study. Subjects completing the Phase III FUEL study will be&#xD;
      eligible for recruitment. Additional subjects will be recruited as needed to ensure a minimum&#xD;
      of 300 total subjects enroll. Safety, pharmacodynamic and quality of life data will be&#xD;
      collected and analyzed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Actual">March 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety (Adverse Events)</measure>
    <time_frame>52 Weeks</time_frame>
    <description>Adverse Events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Exercise (Change in maximal oxygen consumption)</measure>
    <time_frame>52 Weeks</time_frame>
    <description>Change in maximal oxygen consumption.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Echo (Change in myocardial performance Index)</measure>
    <time_frame>52 Weeks</time_frame>
    <description>Change in myocardial performance Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial function (Change in log-transformed Reactive Hyperemia Index)</measure>
    <time_frame>52 Weeks</time_frame>
    <description>Change in log-transformed Reactive Hyperemia Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Function Health Status (Change in full scale Peds QL)</measure>
    <time_frame>52 Weeks</time_frame>
    <description>Change in full scale Peds QL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers (Change in serum BNP level)</measure>
    <time_frame>52 Weeks</time_frame>
    <description>Change in serum BNP level from baseline to end-of-study</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">300</enrollment>
  <condition>Functional Single Ventricle Heart Disease</condition>
  <arm_group>
    <arm_group_label>Drug</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Udenafil administered for 52 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Udenafil</intervention_name>
    <description>Active drug</description>
    <arm_group_label>Drug</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females with Fontan physiology who participated in the FUEL trial or, if&#xD;
             they did not participate in FUEL, those who are 12 to less than 19 years of age at&#xD;
             enrollment.&#xD;
&#xD;
          2. Participant consent or parental/guardian consent and participant assent.&#xD;
&#xD;
          3. Participant fluent in English, Spanish, or Korean.&#xD;
&#xD;
          4. Current anti-platelet or anticoagulant therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Height &lt; 132 cm.&#xD;
&#xD;
          2. Weight &lt; 40 kg.&#xD;
&#xD;
          3. Hospitalization for acute decompensated heart failure within the last 12 months.&#xD;
&#xD;
          4. Current intravenous inotropic drugs.&#xD;
&#xD;
          5. Undergoing evaluation for heart transplantation or listed for transplantation.&#xD;
&#xD;
          6. Diagnosis of active protein losing enteropathy or plastic bronchitis within the last&#xD;
             three years, or a history of liver cirrhosis.&#xD;
&#xD;
          7. Known Fontan baffle obstruction, branch pulmonary artery stenosis, or pulmonary vein&#xD;
             stenosis resulting in a mean gradient of &gt; 4 mm Hg between the regions proximal and&#xD;
             distal to the obstruction as measured by either catheterization or echocardiography.&#xD;
&#xD;
          8. Single lung physiology.&#xD;
&#xD;
          9. Maximal VO2 less than 50% of predicted for age and gender at enrollment.&#xD;
&#xD;
         10. Severe ventricular dysfunction assessed qualitatively by clinical echocardiography&#xD;
             within six months prior to enrollment.&#xD;
&#xD;
         11. Severe valvar regurgitation, ventricular outflow obstruction, or aortic arch&#xD;
             obstruction assessed by clinical echocardiography within six months prior to&#xD;
             enrollment.&#xD;
&#xD;
         12. Significant renal, hepatic, gastrointestinal or biliary disorders that could impair&#xD;
             absorption, metabolism or excretion of orally administered medications.&#xD;
&#xD;
         13. Inability to complete exercise testing at baseline screening.&#xD;
&#xD;
         14. History of PDE-5 inhibitor use (with the exception of FUEL participation) within 3&#xD;
             months before study onset.&#xD;
&#xD;
         15. Use of any other drug to treat pulmonary hypertension within 3 months before study&#xD;
             onset.&#xD;
&#xD;
         16. Known intolerance to oral udenafil.&#xD;
&#xD;
         17. Frequent use of medications or other substances that inhibit or induce CYP3A4.&#xD;
&#xD;
         18. Current use of alpha-blockers or nitrates.&#xD;
&#xD;
         19. Ongoing or planned participation in another research protocol that would either&#xD;
             prevent successful completion of planned study testing or invalidate its results.&#xD;
&#xD;
         20. Noncardiac medical, psychiatric, and/or social disorder that would prevent successful&#xD;
             completion of planned study testing or would invalidate its results.&#xD;
&#xD;
         21. Cardiac care, ongoing or planned, at a non-study center that would impede study&#xD;
             completion.&#xD;
&#xD;
         22. For females: Pregnancy at the time of screening, pregnancy planned before study&#xD;
             completion, or refusal to use an acceptable method of contraception for study&#xD;
             duration.&#xD;
&#xD;
         23. Unable to abstain or limit intake of grapefruit juice during the duration of the&#xD;
             trial.&#xD;
&#xD;
         24. Refusal to provide written informed consent/assent.&#xD;
&#xD;
         25. In the opinion of the primary care physician, the subject is likely to be&#xD;
             non-compliant with the study protocol.&#xD;
&#xD;
         26. History of clinically significant thromboembolic event, as adjudicated by study&#xD;
             Investigators.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steve Paridon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Philadelphia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Phoenix Children's Hospital/Children's Heart Center at Phoenix Children's Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars/Sinai Heart Institute</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rady Children's Hospital</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemours Cardiac Center/Alfred I. duPont Hospital for Children</name>
      <address>
        <city>Wilmington</city>
        <state>Delaware</state>
        <zip>19803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins All Children's Heart Institute</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riley Hospital for Children/Herman B. Wells Center for Pediatric Research</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Congenital Heart Center/C.S. Mott Children's Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109-4204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Mercy Hospital Kansas City</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University St. Louis/St.Louis Children's Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of New York</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children's Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Primary Children's Medical Hospital/Dept. of Pediatric Cardiology</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Children's Hosptial</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>ON M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sejong General Hospital</name>
      <address>
        <city>Bucheon-si</city>
        <state>Gyeonggi-do</state>
        <zip>14754</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Children's Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Korea, Republic of</country>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>November 22, 2020</last_update_submitted>
  <last_update_submitted_qc>November 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 24, 2020</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>Heart Diseases</mesh_term>
    <mesh_term>Univentricular Heart</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Udenafil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03013751
org study id: PHN-Udenafil-03
secondary id: U01HL068270
nct id: NCT03013751
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
This study is a 12-month (52 week) safety extension study to supplement the FUEL Phase III
      clinical trial to provide safety information regarding the long-term use of udenafil in
      adolescents with single ventricle congenital heart disease.
This will be an open-label extension study. All enrolled subjects will be provided with
      udenafil for the duration of the study. Subjects completing the Phase III FUEL study will be
      eligible for recruitment. Additional subjects will be recruited as needed to ensure a minimum
      of 300 total subjects enroll. Safety, pharmacodynamic and quality of life data will be
      collected and analyzed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety (Adverse Events)
time frame: 52 Weeks
description: Adverse Events
measure: Exercise (Change in maximal oxygen consumption)
time frame: 52 Weeks
description: Change in maximal oxygen consumption.
measure: Echo (Change in myocardial performance Index)
time frame: 52 Weeks
description: Change in myocardial performance Index
measure: Endothelial function (Change in log-transformed Reactive Hyperemia Index)
time frame: 52 Weeks
description: Change in log-transformed Reactive Hyperemia Index
measure: Function Health Status (Change in full scale Peds QL)
time frame: 52 Weeks
description: Change in full scale Peds QL
measure: Biomarkers (Change in serum BNP level)
time frame: 52 Weeks
description: Change in serum BNP level from baseline to end-of-study
arm group label: Drug
arm group type: Experimental
description: Udenafil administered for 52 weeks
intervention type: Drug
intervention name: Udenafil
description: Active drug
arm group label: Drug
criteria: 
gender: All
minimum age: 12 Years
maximum age: 18 Years
healthy volunteers: No
last name: Steve Paridon, MD
role: Principal Investigator
affiliation: Children's Hospital of Philadelphia
facility: 
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country: Canada
country: Korea, Republic of
country: United States
responsible party type: Sponsor
mesh term: Heart Diseases
mesh term: Univentricular Heart
mesh term: Udenafil
sharing ipd: Undecided