Single Ventricle Heart Disease After Fontan SurgeryPhase 1/2NCT02201342
Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents
A Phase 1/2 study testing Udenafil in people with Single Ventricle Heart Disease After Fontan Surgery, run by Mezzion Pharma Co. Ltd at 6 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 14 to 18 years
- Conditions the study is for
- Single Ventricle Heart Disease After Fontan Surgery
- What is being tested?
- Udenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Jul 2014to Apr 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Males and females with Fontan physiology who are 14-18 years of age.
- Willingness to return to center to complete blood draws and exercise tests as described in the study protocol.
- Patients must agree to abstain from alcohol, caffeinated beverages, and grapefruit juice for the duration of the trial.
- Informed assent from subject informed consent from parent/legal guardian as appropriate.
Who cannot join
- Non-cardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results.
- Height <132 cm (minimum height requirement for exercise stress testing).
- 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.
- Single lung physiology.
- Severe ventricular dysfunction or valvular regurgitation (systemic atrioventricular or semilunar valve) determined from review of the echocardiogram performed in closest proximity to study enrollment.
- 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.
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- Hospitalization for acute decompensated heart failure within the 12 months preceding study enrollment.
- A diagnosis of active protein losing enteropathy or plastic bronchitis.
- Active evaluation or listing for heart transplant.
- History of use of a phosphodiesterase type 5 inhibitor within three months of study enrollment.
- Concurrent illness that, in the opinion of the investigator, precludes participation.
- Current therapy with alpha-blockers or nitrates.
- Pregnancy at the time of enrollment.
- Latex allergy
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
University of Michigan Congenital Heart Center
Ann Arbor, Michigan, 48109-4204
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Riley Hospital for Children
Indianapolis, Indiana, 46201
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Primary Children's Medical Center
Salt Lake City, Utah, 84113
About this study
Official title: 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.
Read the 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
- Being tested
- Udenafil
- Keywords
- Fontan, Pharmacokinetics, Pharmacodynamics, Exercise capacity, Maximal Oxygen Consumption, Vascular function, EndoPAT, Myocardial performance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UdenafilDrug
Drug
| Study group | Role | What they receive |
|---|---|---|
| Udenafil 37.5 mg QD | Experimental | Udenafil 37.5 mg tablet once daily for 5 days Receives: Drug: Udenafil |
| Udenafil 37.5 mg BID | Experimental | Udenafil 37.5 mg tablet twice daily for 5 days Receives: Drug: Udenafil |
| Udenafil 87.5 mg QD | Experimental | Udenafil 87.5 mg tablet once daily for 5 days Receives: Drug: Udenafil |
| Udenafil 87.5 mg BID | Experimental | Udenafil 87.5 mg tablet twice daily for 5 days Receives: Drug: Udenafil |
| Udenafil 125 mg QD | Experimental | Udenafil 125 mg tablet once daily for 5 days Receives: Drug: Udenafil |
| No Drug | No intervention | Cohort undergoing exercise test only |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Serious Adverse Events Possibly or Probably Related to Udenafil
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.
Measured: 5 days
Secondary outcomes (12)
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: Cmax
Evaluate the pharmacokinetic (PK) profile of udenafil, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Measured: Day 5, zero to 48 hours after the last dose
Evaluate the Effect of Udenafil on Pharmacodynamic (PD) Outcomes: Exercise Capacity
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].
Measured: Day 1 (baseline) and Day 5 (follow-up)
Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: Cmax
Evaluate the pharmacokinetic (PK) profile of metabolite DA-8164, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Measured: Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: Tmax
Evaluate the pharmacokinetic (PK) profile of udenafil, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Measured: Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: T-1/2
Evaluate the pharmacokinetic (PK) profile of udenafil, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Measured: Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: AUC (0-tau)
Evaluate the pharmacokinetic (PK) profile of udenafil, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Measured: Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: CLSS/F
Evaluate the pharmacokinetic (PK) profile of udenafil, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Measured: 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)]
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.
Measured: Day 1 (baseline) and Day 5 (follow-up)
Absolute Change in Blood Pool Myocardial Performance Index (MPI)
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.
Measured: Day 1 (baseline) and Day 5 (follow-up)
Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: Tmax
Evaluate the pharmacokinetic (PK) profile of metabolite DA-8164, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Measured: Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: T-1/2
Evaluate the pharmacokinetic (PK) profile of metabolite DA-8164, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Measured: Day 5, zero to 48 hours after the last dose
Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: AUC(0-tau)
Evaluate the pharmacokinetic (PK) profile of metabolite DA-8164, by weight, age, and gender in adolescents with Fontan physiology at multiple dosing levels.
Measured: Day 5, zero to 48 hours after the last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Single Ventricle Heart Disease After Fontan SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mezzion Pharma Co. Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Pediatric Heart Network
- Responsible party
- Sponsor
- Investigators
- David Goldberg, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02201342
- Sponsor's protocol ID
- PHN-Udenafil-01
- Other IDs
- U01HL068270
- Status last verified
- Apr 2025
- First submitted
- 24 Jul 2014
- Last updated
- 6 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Dose Escalation Trial of Udenafil in Adolescents With Single Ventricle Physiology After Fontan Palliation
- ClinicalTrials.gov ID
- NCT02201342
- Acronym / sponsor ID
- PHN-Udenafil-01
- Keywords
- Fontan, Pharmacokinetics, Pharmacodynamics, Exercise capacity, Maximal Oxygen Consumption, Vascular function, EndoPAT, Myocardial performance
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Mezzion Pharma Co. LtdIndustry (pharma, biotech, devices)
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Pediatric Heart Network
- Study start
- Jul 2014
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 28 Jul 2014 (estimated)
- Results
- Posted 6 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Udenafil 37.5 mg QD | Experimental | Drug: UdenafilUdenafil 37.5 mg tablet once daily for 5 days |
| Udenafil 37.5 mg BID | Experimental | Drug: UdenafilUdenafil 37.5 mg tablet twice daily for 5 days |
| Udenafil 87.5 mg QD | Experimental | Drug: UdenafilUdenafil 87.5 mg tablet once daily for 5 days |
| Udenafil 87.5 mg BID | Experimental | Drug: UdenafilUdenafil 87.5 mg tablet twice daily for 5 days |
| Udenafil 125 mg QD | Experimental | Drug: UdenafilUdenafil 125 mg tablet once daily for 5 days |
| No Drug | No intervention | –Cohort undergoing exercise test only |
Who may qualify
- Ages
- 14 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Males and females with Fontan physiology who are 14-18 years of age.
- Willingness to return to center to complete blood draws and exercise tests as described in the study protocol.
- Patients must agree to abstain from alcohol, caffeinated beverages, and grapefruit juice for the duration of the trial.
- Informed assent from subject informed consent from parent/legal guardian as appropriate.
Key exclusion criteria (14 listed)
- Non-cardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results.
- Height <132 cm (minimum height requirement for exercise stress testing).
- 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.
- Single lung physiology.
- Severe ventricular dysfunction or valvular regurgitation (systemic atrioventricular or semilunar valve) determined from review of the echocardiogram performed in closest proximity to study enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UdenafilDrug | Drug | Udenafil 125 mg QD, Udenafil 37.5 mg BID, Udenafil 37.5 mg QD, Udenafil 87.5 mg BID, Udenafil 87.5 mg QD |
Primary outcome
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.
12 secondary outcomes
Evaluate the Pharmacokinetic (PK) Profile of Udenafil: Cmax
Time frame: 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 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 Udenafil: Tmax
Time frame: 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: AUC (0-tau)
Time frame: 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 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)
Absolute Change in Blood Pool Myocardial Performance Index (MPI)
Time frame: 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: T-1/2
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Goldberg, MD principal investigator
Children's Hospital of Philadelphia
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Udenafil in people with Single Ventricle Heart Disease After Fontan Surgery, run by Mezzion Pharma Co. Ltd at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Serious Adverse Events Possibly or Probably Related to Udenafil (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2025.