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Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents

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ClinicalTrials.gov Identifier: NCT02201342
Recruitment Status : Completed
First Posted : July 28, 2014
Last Update Posted : April 27, 2015
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Pediatric Heart Network
Information provided by (Responsible Party):
Mezzion Pharma Co. Ltd

Brief 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.

Condition or disease Intervention/treatment Phase
Single Ventricle Heart Disease After Fontan Surgery Drug: Udenafil Phase 1 Phase 2

Detailed 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Dose Escalation Trial of Udenafil in Adolescents With Single Ventricle Physiology After Fontan Palliation
Study Start Date : July 2014
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Udenafil Dose Level 1 qd
Udenafil tablet dose Level 1 daily for 5 days
Drug: Udenafil
Drug

Experimental: Udenafil Dose Level 1 bid
Udenafil Dose Level 1 twice daily for 5 days.
Drug: Udenafil
Drug

Experimental: Udenafil Dose Level 2 qd
Udenafil tablet dose level 2 once daily for 5 days.
Drug: Udenafil
Drug

Experimental: Udenafil Dose Level 2 bid
Udenafil tablet dose level 2 twice daily for 5 days
Drug: Udenafil
Drug

Experimental: Udenafil Dose Level 3 qd
Udenafil tablet dose level 3 daily for 5 days
Drug: Udenafil
Drug

No Intervention: No Drug
No drug



Primary Outcome Measures :
  1. Number of subjects with Serious Adverse Events [ Time Frame: 5 days ]
    Safety will be measured by the number of subjects experience serious adverse events possibly or probably related to study drug


Secondary Outcome Measures :
  1. Plasma clearance of parent drug and active metabolite [ Time Frame: Day 5, Zero to 48 hours post last dose ]
    Plasma clearance of parent drug and active metabolite will be determine after the administration of the last dose on day 5.

  2. Measurement of maximum oxygen consumption (VO2) [ Time Frame: Day 1 and Day 5 ]
    Change in maximum oxygen consumption after standard exercise testing.

  3. PAT Index [ Time Frame: Day 1 and Day 5 ]
    Measurement of the PAT reactive hyperemia index by the EndoPAT device.

  4. Myocardial Performance Index (MPI) [ Time Frame: Day 1 and Day 5 ]
    Myocardial Performance Index determined by echocardiogram.



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Ages Eligible for Study:   14 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02201342


Locations
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United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46201
United States, Michigan
University of Michigan Congenital Heart Center
Ann Arbor, Michigan, United States, 48109-4204
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G1X8
Sponsors and Collaborators
Mezzion Pharma Co. Ltd
National Heart, Lung, and Blood Institute (NHLBI)
Pediatric Heart Network
Investigators
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Principal Investigator: David Goldberg, MD Children's Hospital of Philadelphia
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Responsible Party: Mezzion Pharma Co. Ltd
ClinicalTrials.gov Identifier: NCT02201342    
Other Study ID Numbers: PHN-Udenafil-01
U01HL068270 ( U.S. NIH Grant/Contract )
First Posted: July 28, 2014    Key Record Dates
Last Update Posted: April 27, 2015
Last Verified: April 2015
Keywords provided by Mezzion Pharma Co. Ltd:
Fontan
Pharmacokinetics
Pharmacodynamics
Exercise capacity
Maximal Oxygen Consumption
Vascular function
EndoPAT
Myocardial performance
Additional relevant MeSH terms:
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Heart Diseases
Cardiovascular Diseases
Udenafil
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action