Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents

April 18, 2025 updated by: Mezzion Pharma Co. Ltd

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G1X8
        • The Hospital for Sick Children
  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46201
        • Riley Hospital for Children
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-4204
        • University of Michigan Congenital Heart Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

10 years to 14 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Udenafil 37.5 mg QD
Udenafil 37.5 mg tablet once daily for 5 days
Drug: Udenafil
Drug
Experimental: Udenafil 37.5 mg BID
Udenafil 37.5 mg tablet twice daily for 5 days
Drug: Udenafil
Drug
Experimental: Udenafil 87.5 mg QD
Udenafil 87.5 mg tablet once daily for 5 days
Drug: Udenafil
Drug
Experimental: Udenafil 87.5 mg BID
Udenafil 87.5 mg tablet twice daily for 5 days
Drug: Udenafil
Drug
Experimental: Udenafil 125 mg QD
Udenafil 125 mg tablet once daily for 5 days
Drug: Udenafil
Drug
No Intervention: No Drug
Cohort undergoing exercise test only

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Subjects With Serious Adverse Events Possibly or Probably Related to Udenafil
Time Frame: 5 days
Number of subjects experiencing serious adverse events possibly or probably related to udenafil at doses of 37.5 mg daily, 37.5 mg twice daily, 87.5 mg daily, 87.5 mg twice daily, and 125 mg daily given over a five-day period.
5 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: Cmax
Time Frame: Day 5, zero to 48 hours after the last dose
Evaluate the pharmacokinetic (PK) profile of udenafil, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Day 5, zero to 48 hours after the last dose
Evaluate the Effect of Udenafil on Pharmacodynamic (PD) Outcomes: Exercise Capacity
Time Frame: Day 1 (baseline) and Day 5 (follow-up)
Evaluate the effect of udenafil on pharmacodynamic (PD) outcomes including: exercise capacity, vascular function, and echocardiographic measures of myocardial performance (MPI). The outcome measures (OM) are a difference between baseline (BL) and follow-up (FU) [OM = FU-BL].
Day 1 (baseline) and Day 5 (follow-up)
Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: Cmax
Time Frame: Day 5, zero to 48 hours after the last dose
Evaluate the pharmacokinetic (PK) profile of metabolite DA-8164, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: Tmax
Time Frame: Day 5, zero to 48 hours after the last dose
Evaluate the pharmacokinetic (PK) profile of udenafil, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: T-1/2
Time Frame: Day 5, zero to 48 hours after the last dose
Evaluate the pharmacokinetic (PK) profile of udenafil, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: AUC (0-tau)
Time Frame: Day 5, zero to 48 hours after the last dose
Evaluate the pharmacokinetic (PK) profile of udenafil, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: CLSS/F
Time Frame: Day 5, zero to 48 hours after the last dose
Evaluate the pharmacokinetic (PK) profile of udenafil, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Day 5, zero to 48 hours after the last dose
Evaluate the Effect of Udenafil on Pharmacodynamic (PD) Outcomes: Vascular Function [Change in Natural Log Transformed Reactive Hyperemia Index (RHI)]
Time Frame: Day 1 (baseline) and Day 5 (follow-up)
Evaluate the effect of udenafil on pharmacodynamic (PD) outcomes including: exercise capacity, vascular function, and echocardiographic measures of myocardial performance (MPI). The outcome measures (OM) are a difference between baseline (BL) and follow-up (FU, Day-5) [OM = FU-BL]. Endothelial pulse amplitude tonometry (Endo-PAT) is a technique for the non-invasive assessment of peripheral vascular function. In adults, Endo-PAT has been demonstrated to identify those with coronary artery dysfunction and to correlate with brachial artery reactivity testing. Endo-PAT use in children has been more limited, but has shown excellent reproducibility. Reactive hyperemia index (RHI), a measure of the hyperemic response adjusted for baseline blood flow, is a measure of vascular function. A higher value denotes better, or more healthy, vascular (endothelial) function. The data represents a change in the index value so there is no minimum or maximum value that can be represented on a scale.
Day 1 (baseline) and Day 5 (follow-up)
Absolute Change in Blood Pool Myocardial Performance Index (MPI)
Time Frame: Day 1 (baseline) and Day 5 (follow-up)
The outcome measures (OM) are a difference between baseline (BL) and follow-up (FU, Day-5). Change in the MPI from baseline to Day 5 is determined by velocities from blood pool Doppler of the inflow and outflow tract of the dominant ventricle. The measure is the ratio of the sum of isovolumetric contraction time and isovolumetric relaxation time, divided by ventricular ejection time. A lower value is consistent with a more efficient ventricle (better function). A value of zero indicates that there is no isovolumetric contraction or relaxation and, while physiologically implausible, would be consistent with a perfectly efficient ventricle. In general, a decrease in the MPI corresponds to more efficient (better) ventricular function, while an increase in MPI corresponds to less efficient (worse) ventricular function. The data represents a change in the index value so there is no minimum or maximum value that can be represented on a scale.
Day 1 (baseline) and Day 5 (follow-up)
Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: Tmax
Time Frame: Day 5, zero to 48 hours after the last dose
Evaluate the pharmacokinetic (PK) profile of metabolite DA-8164, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: T-1/2
Time Frame: Day 5, zero to 48 hours after the last dose
Evaluate the pharmacokinetic (PK) profile of metabolite DA-8164, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: AUC(0-tau)
Time Frame: Day 5, zero to 48 hours after the last dose
Evaluate the pharmacokinetic (PK) profile of metabolite DA-8164, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Day 5, zero to 48 hours after the last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mezzion Pharma Co. Ltd

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
Pediatric Heart Network

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: David Goldberg, MD, Children's Hospital of Philadelphia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 24, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 28, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 6, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PHN-Udenafil-01
  • U01HL068270 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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