Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents

Single Ventricle Heart Disease After Fontan Surgery Clinical Trial

Official title:

A Phase I/II Dose Escalation Trial of Udenafil in Adolescents With Single Ventricle Physiology After Fontan Palliation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02201342
• Other study ID #: PHN-Udenafil-01
• Secondary ID: U01HL068270
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 24, 2014
• Last updated: April 24, 2015
• Start date: July 2014
• Est. completion date: April 2015

Study information

• Verified date: April 2015
• Source: Mezzion Pharma Co. Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 18 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Single Ventricle Heart Disease After Fontan Surgery

Intervention

Drug:
• Udenafil
Drug

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	University of Michigan Congenital Heart Center	Ann Arbor	Michigan
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Primary Children's Medical Center	Salt Lake City	Utah

Sponsors (3)

Lead Sponsor	Collaborator
Mezzion Pharma Co. Ltd	National Heart, Lung, and Blood Institute (NHLBI), Pediatric Heart Network

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with Serious Adverse Events	Safety will be measured by the number of subjects experience serious adverse events possibly or probably related to study drug	5 days	Yes
Secondary	Plasma clearance of parent drug and active metabolite	Plasma clearance of parent drug and active metabolite will be determine after the administration of the last dose on day 5.	Day 5, Zero to 48 hours post last dose	No
Secondary	Measurement of maximum oxygen consumption (VO2)	Change in maximum oxygen consumption after standard exercise testing.	Day 1 and Day 5	No
Secondary	PAT Index	Measurement of the PAT reactive hyperemia index by the EndoPAT device.	Day 1 and Day 5	No
Secondary	Myocardial Performance Index (MPI)	Myocardial Performance Index determined by echocardiogram.	Day 1 and Day 5	No