Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents

Mezzion Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Single Ventricle Heart Disease After Fontan Surgery

Treatments: Drug: Udenafil

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02201342

PHN-Udenafil-01

U01HL068270 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 36 patients

Sex: All

Ages: 14 to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 6 patient groups

Udenafil 37.5 mg QD

Experimental group

Description:

Udenafil 37.5 mg tablet once daily for 5 days

Treatment:

Drug: Udenafil

Udenafil 37.5 mg BID

Experimental group

Description:

Udenafil 37.5 mg tablet twice daily for 5 days

Treatment:

Drug: Udenafil

Udenafil 87.5 mg QD

Experimental group

Description:

Udenafil 87.5 mg tablet once daily for 5 days

Treatment:

Drug: Udenafil

Udenafil 87.5 mg BID

Experimental group

Description:

Udenafil 87.5 mg tablet twice daily for 5 days

Treatment:

Drug: Udenafil

Udenafil 125 mg QD

Experimental group

Description:

Udenafil 125 mg tablet once daily for 5 days

Treatment:

Drug: Udenafil

No Drug

No Intervention group

Description:

Cohort undergoing exercise test only