Udenafil for Single Ventricle Heart Disease

(FUEL-2 Trial)

Recruiting at 49 trial locations

Overseen By WG Kim

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Mezzion Pharma Co. Ltd

Must be taking: Antiplatelet, Anticoagulant

Must not be taking: PDE-5 inhibitors, Alpha-blockers

Disqualifiers: Heart failure, Liver cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

436 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests udenafil, an oral medication, to determine its effectiveness and safety for adolescents who have undergone the Fontan procedure, a heart surgery for single ventricle heart disease. Participants will receive either udenafil or a placebo (a pill with no active medicine) for comparison. This study targets individuals aged 12 to under 19 who have had the Fontan procedure and are currently on antiplatelet or anticoagulant therapy (medications that help prevent blood clots). As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on antiplatelet or anticoagulant therapy to participate. You cannot use PDE-5 inhibitors, alpha-blockers, or nitrates during the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that udenafil, the treatment under study, has been well-tolerated in past studies. For example, patients with single ventricle heart disease who took udenafil managed different doses well. Some studies found that udenafil improved exercise capacity in children with heart conditions. Importantly, these studies reported no serious side effects. This suggests that udenafil might be a safe option for treating teenagers who have undergone the Fontan procedure. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Udenafil is unique because it specifically targets blood flow and improves heart function by inhibiting the enzyme phosphodiesterase type 5 (PDE5), which is different from the common surgical interventions or heart medications used for single ventricle heart disease. Researchers are excited about udenafil because it has the potential to improve cardiovascular performance without the need for invasive procedures. This could offer a less burdensome treatment option for patients and potentially improve quality of life with fewer side effects.

What evidence suggests that udenafil might be an effective treatment for single ventricle heart disease?

Research has shown that udenafil, a drug that improves blood flow, may benefit teenagers with single ventricle heart disease who have undergone the Fontan procedure. In this trial, some participants will receive udenafil, while others will receive a placebo. The FUEL trial found that patients taking udenafil exercised better after six months, suggesting the drug may enhance heart efficiency during physical activity. Udenafil relaxes and widens blood vessels, improving circulation. These findings strongly suggest that udenafil could benefit those with this specific heart condition. ^{1 2 3 6 7}

Who Is on the Research Team?

WG Kim

Principal Investigator

Mezzion Pharma Co. Ltd

Are You a Good Fit for This Trial?

Adolescents aged 12-18 with Fontan physiology, fluent in the study country's primary language, on antiplatelet or anticoagulant therapy can join. Excluded are those under 132 cm tall, pregnant females or not using contraception, recent heart failure hospitalization, severe ventricular dysfunction, and certain medication users.

Inclusion Criteria

I am between 12 and 18 years old with Fontan physiology.

Participant fluency in primary language of country in which study is being conducted

Participant consent or parental/guardian consent and participant assent

Exclusion Criteria

I have been diagnosed with protein losing enteropathy, plastic bronchitis in the last 3 years, or have liver cirrhosis.

I do not have severe kidney, liver, or digestive problems that could affect how my body handles medication.

You cannot finish the exercise test during the initial screening.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive udenafil or placebo for 26 weeks

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Udenafil

Trial Overview The trial is testing Udenafil against a placebo to see if it's safe and effective for teens who've had the Fontan procedure. Participants will be randomly assigned to either receive Udenafil or a placebo for comparison.

How Is the Trial Designed?

Group I: Placebo Experimental Treatment 1 Intervention

Approximately 218 subjects dosed with matching placebo will be enrolled at approximately 30 sites.

Group II: Drug Experimental Treatment 1 Intervention

Approximately 218 subjects dosed with udenafil will be enrolled at approximately 30 sites.

Who Is Running the Clinical Trial?

Mezzion Pharma Co. Ltd

Lead Sponsor

Trials

5

Recruited

1,300+

Published Research Related to This Trial

In a multicenter trial with 345 participants, carvedilol significantly improved left ventricular (LV) function and reduced mortality rates in patients with mild to moderate chronic heart failure, with a 73% lower risk of all-cause mortality compared to placebo.

Carvedilol also decreased hospitalization rates by 58% to 64% and was generally well tolerated, indicating its efficacy and safety as a treatment for chronic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Bristow, MR., Gilbert, EM., Abraham, WT., et al.[2022]

In a trial involving 227 patients with chronic stable angina, diltiazem hydrochloride in a once-daily capsule formulation showed a significant linear dose response, improving exercise tolerance and delaying exercise termination time, indicating its efficacy in managing angina symptoms.

The study found that doses up to 240 mg/day improved exercise tolerance without increasing the rate of treatment-related adverse effects compared to placebo, suggesting a favorable safety profile for this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response evaluation of once-daily therapy with a new formulation of diltiazem for stable angina pectoris. Diltiazem CD Study Group. Thadani, U., Glasser, S., Bittar, N., et al.[2019]

In a study of 20 male patients with a history of myocardial infarction, intravenous diltiazem significantly lowered resting blood pressure and systemic vascular resistance while increasing cardiac index, indicating its efficacy in improving hemodynamic parameters.

During exercise, diltiazem further reduced mean pulmonary arterial pressure and total pulmonary resistance, demonstrating its potential to enhance cardiac performance without significantly increasing cardiac workload.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemodynamic effects of diltiazem at rest and during exercise in patients with previous myocardial infarction. Cobelli, F., Opasich, C., Riccardi, G., et al.[2019]

In a study involving 13 anesthetized dogs, amlodipine did not improve vascular capacitance or reduce cardiac filling pressures in a model of acute ischemic heart failure, suggesting it may not have beneficial hemodynamic effects in this condition.

The results indicated a negative inotropic effect of amlodipine in heart failure, as evidenced by decreased left ventricular stroke work in the heart failure group, leaving the mechanism of its benefits in chronic heart failure unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular and cardiac effects of amlodipine in acute heart failure in dogs. Isaac, DL., Belenkie, I., Manyari, DE., et al.[2016]

In a study of 223 patients with moderate chronic congestive heart failure, treatment with the angiotensin converting enzyme inhibitor ramipril resulted in a significant decrease in blood pressure and fewer patients experiencing deterioration in their heart failure classification compared to placebo.

While both groups showed an increase in maximal exercise time, the difference between ramipril and placebo was not statistically significant, suggesting that ramipril's primary benefits may lie in improving heart function and reducing the need for additional heart failure medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of effect on exercise capacity of 12-weeks treatment with ramipril in patients with moderate congestive heart failure. Ramipril Study Group. Gundersen, T., Swedberg, K., Amtorp, O., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5458626/

Results of a Phase I/II Multi-Center Investigation of Udenafil in ... The aims of this study were to: 1) evaluate the short-term safety and tolerability of udenafil in male and female adolescents with single ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9674374/

Impact of Udenafil on Echocardiographic Indices of Single ... The FUEL trial demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID).

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.125.041348

Revisiting the Effect of Udenafil on Exercise Performance ... In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory ...

4. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT02201342

Pharmacokinetic/Pharmacodynamic Study of Udenafil in ... Evaluate the effect of udenafil on pharmacodynamic (PD) outcomes including: exercise capacity, vascular function, and echocardiographic measures of myocardial ...

5. withpower.com withpower.com/trial/phase-3-heart-diseases-8-2023-2a56e

Udenafil for Single Ventricle Heart Disease (FUEL-2 Trial) This trial tests udenafil, a medication that improves blood flow, on adolescents who have had heart surgery (Fontan procedure).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10872492/

The Effect of Udenafil on Heart Rate and Blood Pressure in ... The FUEL trial showed that treatment with udenafil was associated with improved exercise performance at the ventilatory anaerobic threshold in children with ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002870317300789

Results of a phase I/II multi-center investigation of udenafil ... Udenafil was well-tolerated at all dosing levels. The 87.5 mg bid cohort achieved the highest plasma drug level and was associated with a suggestion of ...