<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/NCT02201342</url>
  </required_header>
  <id_info>
    <org_study_id>PHN-Udenafil-01</org_study_id>
    <secondary_id>U01HL068270</secondary_id>
    <nct_id>NCT02201342</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents</brief_title>
  <official_title>A Phase I/II Dose Escalation Trial 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>
    <collaborator>
      <agency>Pediatric Heart Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mezzion Pharma Co. Ltd</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine the pharmacokinetic profile and safety of udenafil in adolescents with Fontan&#xD;
      physiology and to assess the short-term pharmacodynamic effect of udenafil on pharmacodynamic&#xD;
      measures of exercise capacity, ventricular performance, and vascular function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A dose escalation trial to determine the pharmacokinetics, safety and tolerance of udenafil&#xD;
      in male and female adolescent subjects with single ventricle physiology that that have&#xD;
      undergone the Fontan surgical procedure. Pharmacodynamic data will also be collected to&#xD;
      evaluate the effect of udenafil on acute exercise performance, peripheral vascular function&#xD;
      and indices of myocardial performance. Five udenafil cohorts will be evaluated in additional&#xD;
      to one drug free cohort&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects with Serious Adverse Events</measure>
    <time_frame>5 days</time_frame>
    <description>Safety will be measured by the number of subjects experience serious adverse events possibly or probably related to study drug</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma clearance of parent drug and active metabolite</measure>
    <time_frame>Day 5, Zero to 48 hours post last dose</time_frame>
    <description>Plasma clearance of parent drug and active metabolite will be determine after the administration of the last dose on day 5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of maximum oxygen consumption (VO2)</measure>
    <time_frame>Day 1 and Day 5</time_frame>
    <description>Change in maximum oxygen consumption after standard exercise testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PAT Index</measure>
    <time_frame>Day 1 and Day 5</time_frame>
    <description>Measurement of the PAT reactive hyperemia index by the EndoPAT device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial Performance Index (MPI)</measure>
    <time_frame>Day 1 and Day 5</time_frame>
    <description>Myocardial Performance Index determined by echocardiogram.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Single Ventricle Heart Disease After Fontan Surgery</condition>
  <arm_group>
    <arm_group_label>Udenafil Dose Level 1 qd</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Udenafil tablet dose Level 1 daily for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Udenafil Dose Level 1 bid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Udenafil Dose Level 1 twice daily for 5 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Udenafil Dose Level 2 qd</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Udenafil tablet dose level 2 once daily for 5 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Udenafil Dose Level 2 bid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Udenafil tablet dose level 2 twice daily for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Udenafil Dose Level 3 qd</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Udenafil tablet dose level 3 daily for 5 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Drug</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No drug</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Udenafil</intervention_name>
    <description>Drug</description>
    <arm_group_label>Udenafil Dose Level 1 bid</arm_group_label>
    <arm_group_label>Udenafil Dose Level 1 qd</arm_group_label>
    <arm_group_label>Udenafil Dose Level 2 bid</arm_group_label>
    <arm_group_label>Udenafil Dose Level 2 qd</arm_group_label>
    <arm_group_label>Udenafil Dose Level 3 qd</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females with Fontan physiology who are 14-18 years of age.&#xD;
&#xD;
          2. Willingness to return to center to complete blood draws and exercise tests as&#xD;
             described in the study protocol.&#xD;
&#xD;
          3. Patients must agree to abstain from alcohol, caffeinated beverages, and grapefruit&#xD;
             juice for the duration of the trial.&#xD;
&#xD;
          4. Informed assent from subject informed consent from parent/legal guardian as&#xD;
             appropriate.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Non-cardiac medical, psychiatric, and/or social disorder that would prevent successful&#xD;
             completion of planned study testing or would invalidate its results.&#xD;
&#xD;
          2. Height &lt;132 cm (minimum height requirement for exercise stress testing).&#xD;
&#xD;
          3. Known Fontan baffle obstruction, branch pulmonary artery stenosis, or pulmonary vein&#xD;
             stenosis resulting in a mean gradient of &gt;4 mmHg between the regions proximal and&#xD;
             distal to the obstruction.&#xD;
&#xD;
          4. Single lung physiology.&#xD;
&#xD;
          5. Severe ventricular dysfunction or valvular regurgitation (systemic atrioventricular or&#xD;
             semilunar valve) determined from review of the echocardiogram performed in closest&#xD;
             proximity to study enrollment.&#xD;
&#xD;
          6. Significant renal (serum creatinine &gt; 2.0), hepatic (serum aspartate aminotransferase&#xD;
             (AST) and/or alanine aminotransferase ( ALT) &gt; 3 times upper limit of normal),&#xD;
             gastrointestinal or biliary disorders that could impair absorption, metabolism or&#xD;
             excretion of orally administered medications, based on laboratory assessment at the&#xD;
             time of screening visit.&#xD;
&#xD;
          7. Hospitalization for acute decompensated heart failure within the 12 months preceding&#xD;
             study enrollment.&#xD;
&#xD;
          8. A diagnosis of active protein losing enteropathy or plastic bronchitis.&#xD;
&#xD;
          9. Active evaluation or listing for heart transplant.&#xD;
&#xD;
         10. History of use of a phosphodiesterase type 5 inhibitor within three months of study&#xD;
             enrollment.&#xD;
&#xD;
         11. Concurrent illness that, in the opinion of the investigator, precludes participation.&#xD;
&#xD;
         12. Current therapy with alpha-blockers or nitrates.&#xD;
&#xD;
         13. Pregnancy at the time of enrollment.&#xD;
&#xD;
         14. Latex allergy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Goldberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Philadelphia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Riley Hospital for Children</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Congenital Heart Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109-4204</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>Primary Children's Medical Center</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84113</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>M5G1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>April 24, 2015</last_update_submitted>
  <last_update_submitted_qc>April 24, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 27, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fontan</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Pharmacodynamics</keyword>
  <keyword>Exercise capacity</keyword>
  <keyword>Maximal Oxygen Consumption</keyword>
  <keyword>Vascular function</keyword>
  <keyword>EndoPAT</keyword>
  <keyword>Myocardial performance</keyword>
  <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>
  <!-- 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/NCT02201342
org study id: PHN-Udenafil-01
secondary id: U01HL068270
nct id: NCT02201342
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
To determine the pharmacokinetic profile and safety of udenafil in adolescents with Fontan
      physiology and to assess the short-term pharmacodynamic effect of udenafil on pharmacodynamic
      measures of exercise capacity, ventricular performance, and vascular function.
A dose escalation trial to determine the pharmacokinetics, safety and tolerance of udenafil
      in male and female adolescent subjects with single ventricle physiology that that have
      undergone the Fontan surgical procedure. Pharmacodynamic data will also be collected to
      evaluate the effect of udenafil on acute exercise performance, peripheral vascular function
      and indices of myocardial performance. Five udenafil cohorts will be evaluated in additional
      to one drug free cohort
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of subjects with Serious Adverse Events
time frame: 5 days
description: Safety will be measured by the number of subjects experience serious adverse events possibly or probably related to study drug
measure: Plasma clearance of parent drug and active metabolite
time frame: Day 5, Zero to 48 hours post last dose
description: Plasma clearance of parent drug and active metabolite will be determine after the administration of the last dose on day 5.
measure: Measurement of maximum oxygen consumption (VO2)
time frame: Day 1 and Day 5
description: Change in maximum oxygen consumption after standard exercise testing.
measure: PAT Index
time frame: Day 1 and Day 5
description: Measurement of the PAT reactive hyperemia index by the EndoPAT device.
measure: Myocardial Performance Index (MPI)
time frame: Day 1 and Day 5
description: Myocardial Performance Index determined by echocardiogram.
arm group label: Udenafil Dose Level 1 qd
arm group type: Experimental
description: Udenafil tablet dose Level 1 daily for 5 days
arm group label: Udenafil Dose Level 1 bid
arm group type: Experimental
description: Udenafil Dose Level 1 twice daily for 5 days.
arm group label: Udenafil Dose Level 2 qd
arm group type: Experimental
description: Udenafil tablet dose level 2 once daily for 5 days.
arm group label: Udenafil Dose Level 2 bid
arm group type: Experimental
description: Udenafil tablet dose level 2 twice daily for 5 days
arm group label: Udenafil Dose Level 3 qd
arm group type: Experimental
description: Udenafil tablet dose level 3 daily for 5 days
arm group label: No Drug
arm group type: No Intervention
description: No drug
intervention type: Drug
intervention name: Udenafil
description: Drug
arm group label: Udenafil Dose Level 1 bid
arm group label: Udenafil Dose Level 1 qd
arm group label: Udenafil Dose Level 2 bid
arm group label: Udenafil Dose Level 2 qd
arm group label: Udenafil Dose Level 3 qd
criteria: 
gender: All
minimum age: 14 Years
maximum age: 18 Years
healthy volunteers: No
last name: David Goldberg, MD
role: Principal Investigator
affiliation: Children's Hospital of Philadelphia
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Heart Diseases
mesh term: Univentricular Heart
mesh term: Udenafil