A Extension Study of Udenafil in Adolescents (FUELExten)

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

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.

Study Overview

• Status: Unknown
• Conditions: Functional Single Ventricle Heart Disease
• Intervention / Treatment: Drug: Udenafil

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, ON M5G 1X8
      • The Hospital for Sick Children
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Children's Hospital
  • Gyeonggi-do
    • Bucheon-si, Gyeonggi-do, Korea, Republic of, 14754
      • Sejong General Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital/Children's Heart Center at Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States, 90048
      • Cedars/Sinai Heart Institute
    • San Diego, California, United States, 92123
      • Rady Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Cardiac Center/Alfred I. duPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20008
      • Children's National Medical Center
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Heart Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Indiana
    • Indianapolis, Indiana, United States, 46201
      • Riley Hospital for Children/Herman B. Wells Center for Pediatric Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-4204
      • University of Michigan Congenital Heart Center/C.S. Mott Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Washington University St. Louis/St.Louis Children's Hospital
  • New York
    • New York, New York, United States, 10032
      • Children's Hospital of New York
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Medical Hospital/Dept. of Pediatric Cardiology
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hosptial
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Participant consent or parental/guardian consent and participant assent.
3. Participant fluent in English, Spanish, or Korean.
4. Current anti-platelet or anticoagulant therapy.

Exclusion Criteria:

1. Height < 132 cm.
2. Weight < 40 kg.
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 three 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 mm Hg between the regions proximal and distal to the obstruction as measured by either catheterization or echocardiography.
8. Single lung physiology.
9. Maximal VO2 less than 50% of predicted for age and gender at enrollment.
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, hepatic, gastrointestinal or biliary disorders that could impair absorption, metabolism or excretion of orally administered medications.
13. Inability to complete exercise testing at baseline screening.
14. History of PDE-5 inhibitor use (with the exception of FUEL participation) within 3 months before study onset.
15. Use of any other drug to treat 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.
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.
26. History of clinically significant thromboembolic event, as adjudicated by study Investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug; Udenafil administered for 52 weeks	Drug: Udenafil; Active drug

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mezzion Pharma Co. Ltd
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Steve Paridon, MD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• Goldberg DJ, Zak V, Goldstein BH, McCrindle BW, Menon SC, Schumacher KR, Payne RM, Rhodes J, McHugh KE, Penny DJ, Trachtenberg F, Hamstra MS, Richmond ME, Frommelt PC, Files MD, Yeager JL, Pemberton VL, Stylianou MP, Pearson GD, Paridon SM; Pediatric Heart Network Investigators. Design and rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) trial. Am Heart J. 2018 Jul;201:1-8. doi: 10.1016/j.ahj.2018.03.015. Epub 2018 Apr 3.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): March 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: January 5, 2017
• First Submitted That Met QC Criteria: January 5, 2017
• First Posted (Estimate): January 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 24, 2020
• Last Update Submitted That Met QC Criteria: November 22, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Diseases; Univentricular Heart; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Udenafil
• Other Study ID Numbers: PHN-Udenafil-03; U01HL068270 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes