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| ID | Type | Description | Link |
|---|---|---|---|
| U01HL068270 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| Pediatric Heart Network | OTHER |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Udenafil 37.5 mg QD | Experimental | Udenafil 37.5 mg tablet once daily for 5 days |
|
| Udenafil 37.5 mg BID | Experimental | Udenafil 37.5 mg tablet twice daily for 5 days |
|
| Udenafil 87.5 mg QD | Experimental | Udenafil 87.5 mg tablet once daily for 5 days |
|
| Udenafil 87.5 mg BID | Experimental | Udenafil 87.5 mg tablet twice daily for 5 days |
|
| Udenafil 125 mg QD | Experimental | Udenafil 125 mg tablet once daily for 5 days |
|
| No Drug | No Intervention | Cohort undergoing exercise test only |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Udenafil | Drug | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 5, zero to 48 hours after the last dose |
| Evaluate the Effect of Udenafil on Pharmacodynamic (PD) Outcomes: Exercise Capacity |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Goldberg, MD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Riley Hospital for Children | Indianapolis | Indiana | 46201 | United States | ||
| University of Michigan Congenital Heart Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | Udenafil 37.5 mg QD | Udenafil 37.5 mg tablet once daily for 5 days |
| FG001 | Udenafil 37.5 mg BID | Udenafil 37.5 mg tablet twice daily for 5 days |
| FG002 | Udenafil 87.5 mg QD | Udenafil 87.5 mg tablet once daily for 5 days |
| FG003 | Udenafil 87.5 mg BID | Udenafil 87.5 mg tablet twice daily for 5 days |
| FG004 | Udenafil 125 mg mg QD | Udenafil 125 mg tablet once daily for 5 days |
| FG005 | No Drug | Only exercise testing |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Udenafil 37.5 mg QD | Udenafil 37.5 mg tablet once daily for 5 days Udenafil: Drug |
| BG001 | Udenafil 37.5 mg BID | Udenafil 37.5 mg tablet twice daily for 5 days Udenafil: Drug |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | participants | 5 days |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Udenafil 37.5 mg QD | Udenafil 37.5 mg tablet once daily for 5 days | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Altered mental status/mood altered | Psychiatric disorders | Systematic Assessment | Not related to the study drug, per PI. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Won Geun Kim | Mezzion Pharmaceuticals | 3128980292 | wg.kim@mezzion.com |
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| ID | Term |
|---|---|
| C419664 | udenafil |
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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 | 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 | 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 | 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) | 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 | 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)] | 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) | 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 | 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 | 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) | 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 |
| Ann Arbor |
| Michigan |
| 48109-4204 |
| United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Primary Children's Medical Center | Salt Lake City | Utah | 84113 | United States |
| The Hospital for Sick Children | Toronto | Ontario | M5G1X8 | Canada |
| BG002 | Udenafil 87.5 mg QD | Udenafil 87.5 mg tablet once daily for 5 days Udenafil: Drug |
| BG003 | Udenafil 87.5 mg BID | Udenafil 87.5 mg tablet twice daily for 5 days Udenafil: Drug |
| BG004 | Udenafil 125 mg QD | Udenafil 125 mg tablet once daily for 5 days Udenafil: Drug |
| BG005 | No Drug | Cohort undergoing exercise test only |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Udenafil 87.5 mg tablet once daily for 5 days |
| OG003 | Udenafil 87.5 mg BID | Udenafil 87.5 mg tablet twice daily for 5 days |
| OG004 | Udenafil 125 mg QD | Udenafil 125 mg tablet once daily for 5 days |
| OG005 | No Drug | Exercise only |
|
|
| Secondary | 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. | The No Drug Group is not eligible for PK analysis. | Posted | Mean | Standard Deviation | ng/ml | Day 5, zero to 48 hours after the last dose |
|
|
|
| Secondary | 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]. | n= 4 to 5 for some measures | Posted | Mean | Standard Deviation | ml/kg/min | Day 1 (baseline) and Day 5 (follow-up) |
|
|
|
| Secondary | 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. | The No Drug Group is not eligible for PK analysis. | Posted | Mean | Standard Deviation | ng/ml | Day 5, zero to 48 hours after the last dose |
|
|
|
| Secondary | 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. | The No Drug Group is not eligible for PK analysis. | Posted | Mean | Standard Deviation | hr | Day 5, zero to 48 hours after the last dose |
|
|
|
| Secondary | 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. | The No Drug Group is not eligible for PK analysis. | Posted | Mean | Standard Deviation | hr | Day 5, zero to 48 hours after the last dose |
|
|
|
| Secondary | 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. | The No Drug Group is not eligible for PK analysis. | Posted | Mean | Standard Deviation | hr*ng/ml | Day 5, zero to 48 hours after the last dose |
|
|
|
| Secondary | 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. | The No Drug Group is not eligible for PK analysis. | Posted | Mean | Standard Deviation | l/hr | Day 5, zero to 48 hours after the last dose |
|
|
|
| Secondary | 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. | n= 4 to 5 for some measures | Posted | Mean | Standard Deviation | Change in natural log Transformed RHI | Day 1 (baseline) and Day 5 (follow-up) |
|
|
|
| Secondary | 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. | n= 4 to 5 for some measures | Posted | Mean | Standard Deviation | Change in blood pool MPI | Day 1 (baseline) and Day 5 (follow-up) |
|
|
|
| Secondary | 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. | The No Drug Group is not eligible for PK analysis. | Posted | Mean | Standard Deviation | hr | Day 5, zero to 48 hours after the last dose |
|
|
|
| Secondary | 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. | The No Drug Group is not eligible for PK analysis. | Posted | Mean | Standard Deviation | hr | Day 5, zero to 48 hours after the last dose |
|
|
|
| Secondary | 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. | The No Drug Group is not eligible for PK analysis. | Posted | Mean | Standard Deviation | hr*ng/ml | Day 5, zero to 48 hours after the last dose |
|
|
|
| 6 |
| 1 |
| 6 |
| 5 |
| 6 |
| EG001 | Udenafil 37.5 mg BID | Udenafil 37.5 mg tablet twice daily for 5 days | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | Udenafil 87.5 mg QD | Udenafil 87.5 mg tablet once daily for 5 days | 0 | 6 | 0 | 6 | 6 | 6 |
| EG003 | Udenafil 87.5 mg BID | Udenafil 87.5 mg tablet twice daily for 5 days | 0 | 6 | 0 | 6 | 5 | 6 |
| EG004 | Udenafil 125 mg QD | Udenafil 125 mg tablet once daily for 5 days | 0 | 6 | 0 | 6 | 6 | 6 |
| EG005 | No Drug | Exercise only | 0 | 6 | 0 | 6 | 0 | 6 |
|
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Flushing | Blood and lymphatic system disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Spontaneous penile erection | Reproductive system and breast disorders | Systematic Assessment |
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Not provided
|
| VO2 at anaerobic threshold |
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