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Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents

Primary Purpose

Single Ventricle Heart Disease After Fontan Surgery

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Udenafil
Sponsored by
Mezzion Pharma Co. Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Single Ventricle Heart Disease After Fontan Surgery focused on measuring Fontan, Pharmacokinetics, Pharmacodynamics, Exercise capacity, Maximal Oxygen Consumption, Vascular function, EndoPAT, Myocardial performance

Eligibility Criteria

14 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Riley Hospital for Children
  • University of Michigan Congenital Heart Center
  • Cincinnati Children's Hospital Medical Center
  • Children's Hospital of Philadelphia
  • Primary Children's Medical Center
  • The Hospital for Sick Children

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

No Intervention

Arm Label

Udenafil Dose Level 1 qd

Udenafil Dose Level 1 bid

Udenafil Dose Level 2 qd

Udenafil Dose Level 2 bid

Udenafil Dose Level 3 qd

No Drug

Arm Description

Udenafil tablet dose Level 1 daily for 5 days

Udenafil Dose Level 1 twice daily for 5 days.

Udenafil tablet dose level 2 once daily for 5 days.

Udenafil tablet dose level 2 twice daily for 5 days

Udenafil tablet dose level 3 daily for 5 days

No drug

Outcomes

Primary Outcome Measures

Number of subjects with Serious Adverse Events
Safety will be measured by the number of subjects experience serious adverse events possibly or probably related to study drug

Secondary Outcome Measures

Plasma clearance of parent drug and active metabolite
Plasma clearance of parent drug and active metabolite will be determine after the administration of the last dose on day 5.
Measurement of maximum oxygen consumption (VO2)
Change in maximum oxygen consumption after standard exercise testing.
PAT Index
Measurement of the PAT reactive hyperemia index by the EndoPAT device.
Myocardial Performance Index (MPI)
Myocardial Performance Index determined by echocardiogram.

Full Information

First Posted
July 24, 2014
Last Updated
April 24, 2015
Sponsor
Mezzion Pharma Co. Ltd
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Pediatric Heart Network
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1. Study Identification

Unique Protocol Identification Number
NCT02201342
Brief Title
Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents
Official Title
A Phase I/II Dose Escalation Trial of Udenafil in Adolescents With Single Ventricle Physiology After Fontan Palliation
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mezzion Pharma Co. Ltd
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Pediatric Heart Network

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Single Ventricle Heart Disease After Fontan Surgery
Keywords
Fontan, Pharmacokinetics, Pharmacodynamics, Exercise capacity, Maximal Oxygen Consumption, Vascular function, EndoPAT, Myocardial performance

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Udenafil Dose Level 1 qd
Arm Type
Experimental
Arm Description
Udenafil tablet dose Level 1 daily for 5 days
Arm Title
Udenafil Dose Level 1 bid
Arm Type
Experimental
Arm Description
Udenafil Dose Level 1 twice daily for 5 days.
Arm Title
Udenafil Dose Level 2 qd
Arm Type
Experimental
Arm Description
Udenafil tablet dose level 2 once daily for 5 days.
Arm Title
Udenafil Dose Level 2 bid
Arm Type
Experimental
Arm Description
Udenafil tablet dose level 2 twice daily for 5 days
Arm Title
Udenafil Dose Level 3 qd
Arm Type
Experimental
Arm Description
Udenafil tablet dose level 3 daily for 5 days
Arm Title
No Drug
Arm Type
No Intervention
Arm Description
No drug
Intervention Type
Drug
Intervention Name(s)
Udenafil
Intervention Description
Drug
Primary Outcome Measure Information:
Title
Number of subjects with Serious Adverse Events
Description
Safety will be measured by the number of subjects experience serious adverse events possibly or probably related to study drug
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Plasma clearance of parent drug and active metabolite
Description
Plasma clearance of parent drug and active metabolite will be determine after the administration of the last dose on day 5.
Time Frame
Day 5, Zero to 48 hours post last dose
Title
Measurement of maximum oxygen consumption (VO2)
Description
Change in maximum oxygen consumption after standard exercise testing.
Time Frame
Day 1 and Day 5
Title
PAT Index
Description
Measurement of the PAT reactive hyperemia index by the EndoPAT device.
Time Frame
Day 1 and Day 5
Title
Myocardial Performance Index (MPI)
Description
Myocardial Performance Index determined by echocardiogram.
Time Frame
Day 1 and Day 5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Goldberg, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46201
Country
United States
Facility Name
University of Michigan Congenital Heart Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-4204
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Primary Children's Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G1X8
Country
Canada

12. IPD Sharing Statement

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Pharmacokinetic/Pharmacodynamic Study of Udenafil in Adolescents

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