Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents

NCT02201342 | Completed Phase 1 Results DMC

• 2 other identifiers: PHN-Udenafil-01U01HL068270
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 6

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.

Conditions

Single Ventricle Heart Disease After Fontan Surgery

Keywords

Fontan; Pharmacokinetics; Pharmacodynamics; Exercise capacity; Maximal Oxygen Consumption; Vascular function; EndoPAT; Myocardial performance

Outcome Measures

Primary Outcomes (1)

• 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.

  5 days

Secondary Outcomes (12)

• Evaluate the Pharmacokinetic (PK) Profile of Udenafil: Cmax

  Day 5, zero to 48 hours after the last dose

• Evaluate the Effect of Udenafil on Pharmacodynamic (PD) Outcomes: Exercise Capacity

  Day 1 (baseline) and Day 5 (follow-up)

• Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: Cmax

  Day 5, zero to 48 hours after the last dose

• Evaluate the Pharmacokinetic (PK) Profile of Udenafil: Tmax

  Day 5, zero to 48 hours after the last dose

• Evaluate the Pharmacokinetic (PK) Profile of Udenafil: T-1/2

  Day 5, zero to 48 hours after the last dose

Study Arms (6)

Udenafil 37.5 mg QD

EXPERIMENTAL

Udenafil 37.5 mg tablet once daily for 5 days

Drug: Udenafil

Udenafil 37.5 mg BID

EXPERIMENTAL

Udenafil 37.5 mg tablet twice daily for 5 days

Drug: Udenafil

Udenafil 87.5 mg QD

EXPERIMENTAL

Udenafil 87.5 mg tablet once daily for 5 days

Drug: Udenafil

Udenafil 87.5 mg BID

EXPERIMENTAL

Udenafil 87.5 mg tablet twice daily for 5 days

Drug: Udenafil

Udenafil 125 mg QD

EXPERIMENTAL

Udenafil 125 mg tablet once daily for 5 days

Drug: Udenafil

No Drug

NO INTERVENTION

Cohort undergoing exercise test only

Interventions

Udenafil DRUG

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

Eligibility Criteria

• Age: 14 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Mezzion Pharma Co. Ltd: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Pediatric Heart Network: collaborator

Study Sites (6)

Riley Hospital for Children

Indianapolis, Indiana, 46201, United States

Location

University of Michigan Congenital Heart Center

Ann Arbor, Michigan, 48109-4204, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

MeSH Terms

Interventions

udenafil

Results Point of Contact

• Title: Won Geun Kim
• Organization: Mezzion Pharmaceuticals

wg.kim@mezzion.com

3128980292

Study Officials

• David Goldberg, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2014
• First Posted: July 28, 2014
• Study Start: July 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: May 6, 2025
• Results First Posted: May 6, 2025

Record last verified: 2025-04

Locations

CA (1); US (5)