A Extension Study of Udenafil in Adolescents

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase III Extension Study of Udenafil in Adolescents With Single Ventricle Physiology After Fontan Palliation

Conditions
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Functional Single Ventricle Heart Disease

Intervention / Treatment
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* Drug: Udenafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females with Fontan physiology who participated in the FUEL trial or, if they did not participate in FUEL, those who are 12 to less than 19 years of age at enrollment. Participant consent or parental/guardian consent and participant assent. Participant fluent in English, Spanish, or Korean. Current anti-platelet or anticoagulant therapy. Exclusion Criteria: Height < 132 cm. Weight < 40 kg. Hospitalization for acute decompensated heart failure within the last 12 months. Current intravenous inotropic drugs. Undergoing evaluation for heart transplantation or listed for transplantation. Diagnosis of active protein losing enteropathy or plastic bronchitis within the last three years, or a history of liver cirrhosis. Known Fontan baffle obstruction, branch pulmonary artery stenosis, or pulmonary vein stenosis resulting in a mean gradient of > 4 mm Hg between the regions proximal and distal to the obstruction as measured by either catheterization or echocardiography. Single lung physiology. Maximal VO2 less than 50% of predicted for age and gender at enrollment. Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within six months prior to enrollment. Severe valvar regurgitation, ventricular outflow obstruction, or aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment. Significant renal, hepatic, gastrointestinal or biliary disorders that could impair absorption, metabolism or excretion of orally administered medications. Inability to complete exercise testing at baseline screening. History of PDE-5 inhibitor use (with the exception of FUEL participation) within 3 months before study onset. Use of any other drug to treat pulmonary hypertension within 3 months before study onset. Known intolerance to oral udenafil. Frequent use of medications or other substances that inhibit or induce CYP3A4. Current use of alpha-blockers or nitrates. Ongoing or planned participation in another research protocol that would either prevent successful completion of planned study testing or invalidate its results. Noncardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results. Cardiac care, ongoing or planned, at a non-study center that would impede study completion. For females: Pregnancy at the time of screening, pregnancy planned before study completion, or refusal to use an acceptable method of contraception for study duration. Unable to abstain or limit intake of grapefruit juice during the duration of the trial. Refusal to provide written informed consent/assent. In the opinion of the primary care physician, the subject is likely to be non-compliant with the study protocol. History of clinically significant thromboembolic event, as adjudicated by study Investigators.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug<br>Udenafil administered for 52 weeks | Drug: Udenafil<br>* Active drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (Adverse Events) | Adverse Events | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise (Change in maximal oxygen consumption) | Change in maximal oxygen consumption. | 52 Weeks | 
| Echo (Change in myocardial performance Index) | Change in myocardial performance Index | 52 Weeks | 
| Endothelial function (Change in log-transformed Reactive Hyperemia Index) | Change in log-transformed Reactive Hyperemia Index | 52 Weeks | 
| Function Health Status (Change in full scale Peds QL) | Change in full scale Peds QL | 52 Weeks | 
| Biomarkers (Change in serum BNP level) | Change in serum BNP level from baseline to end-of-study | 52 Weeks |