Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents

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

Inclusion Criteria:

1. Males and females with Fontan physiology who are 14-18 years of age.

2. Willingness to return to center to complete blood draws and exercise tests as
described in the study protocol.

3. Patients must agree to abstain from alcohol, caffeinated beverages, and grapefruit
juice for the duration of the trial.

4. Informed assent from subject informed consent from parent/legal guardian as
appropriate.

Exclusion Criteria:

1. Non-cardiac medical, psychiatric, and/or social disorder that would prevent
successful completion of planned study testing or would invalidate its results.

2. Height <132 cm (minimum height requirement for exercise stress testing).

3. 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.

4. Single lung physiology.

5. Severe ventricular dysfunction or valvular regurgitation (systemic atrioventricular
or semilunar valve) determined from review of the echocardiogram performed in closest
proximity to study enrollment.

6. Significant renal (serum creatinine > 2.0), hepatic (serum aspartate aminotransferase
(AST) and/or alanine aminotransferase ( 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 at the
time of screening visit.

7. Hospitalization for acute decompensated heart failure within the 12 months preceding
study enrollment.

8. A diagnosis of active protein losing enteropathy or plastic bronchitis.

9. Active evaluation or listing for heart transplant.

10. History of use of a phosphodiesterase type 5 inhibitor within three months of study
enrollment.

11. Concurrent illness that, in the opinion of the investigator, precludes participation.

12. Current therapy with alpha-blockers or nitrates.

13. Pregnancy at the time of enrollment.

14. Latex allergy