Fontan Udenafil Exercise Longitudinal Assessment Trial

This study is a randomized, double-blinded, efficacy trial of the effects of udenafil vs.
placebo on the background of standard therapy on maximal VO2 (ml/kg/min) from baseline to six
months in adolescent survivors of the Fontan procedure. . The target sample size is 400
subjects (200 per group).

Inclusion Criteria:

1. Males and females with Fontan physiology who are 12 to less than 19 years of age at
enrollment.

2. Participant consent or parental/guardian consent and participant assent

3. Participant fluency in primary language of country in which study is being conducted

Exclusion Criteria:

1. Weight < 40 kg

2. Height < 132 cm.

3. Hospitalization for acute decompensated heart failure within the last 12 months.

4. Current intravenous inotropic drugs.

5. Undergoing evaluation for heart transplantation or listed for transplantation.

6. Diagnosis of active protein losing enteropathy or plastic bronchitis within the last 3
years, or a history of liver cirrhosis.

7. Known Fontan baffle obstruction, branch pulmonary artery stenosis, or pulmonary vein
stenosis resulting in a mean gradient of > 4 mmHg between the regions proximal and
distal to the obstruction as measured by either catheterization or echocardiography,
obtained prior to screening for the trial.

8. Single lung physiology with greater than 80% flow to one lung.

9. VO2 less than 50%

10. Severe ventricular dysfunction assessed qualitatively by clinical echocardiography
within six months prior to enrollment.

11. Severe valvar regurgitation, ventricular outflow obstruction, or aortic arch
obstruction assessed by clinical echocardiography within six months prior to
enrollment.

12. Significant renal (serum creatinine > 2.0), hepatic (serum AST and/or ALT > 3 times
upper limit of normal), gastrointestinal or biliary disorders that could impair
absorption, metabolism or excretion of orally administered medications, based on
laboratory assessment six weeks prior to screening for the trial.

13. Inability to complete exercise testing at baseline screening.

14. History of PDE-5 inhibitor use within 3 months before study onset.

15. History of any other medication for treatment of pulmonary hypertension within 3
months before study onset.

16. Known intolerance to oral udenafil.

17. Frequent use of medications or other substances that inhibit or induce CYP3A4.

18. Current use of alpha-blockers or nitrates.

19. Ongoing or planned participation in another research protocol that would either
prevent successful completion of planned study testing or invalidate its results.

20. Noncardiac medical, psychiatric, and/or social disorder that would prevent successful
completion of planned study testing or would invalidate its results.

21. Cardiac care, ongoing or planned, at a non-study center that would impede study
completion.

22. 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
if sexually active.

23. Unable to abstain or limit intake of grapefruit juice during the duration of the
trial.

24. Refusal to provide written informed consent/assent.

25. In the opinion of the primary care physician, the subject is likely to be
non-compliant with the study protocol.