A Phase I/II Dose Escalation Trial of Udenafil in Adolescents With Single Ventricle Physiology After Fontan Palliation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 6
- 主要终点
- Number of Subjects With Serious Adverse Events Possibly or Probably Related to Udenafil
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Udenafil 37.5 mg QD
Udenafil 37.5 mg tablet once daily for 5 days
干预措施: Udenafil (Drug)
Udenafil 37.5 mg BID
Udenafil 37.5 mg tablet twice daily for 5 days
干预措施: Udenafil (Drug)
Udenafil 87.5 mg QD
Udenafil 87.5 mg tablet once daily for 5 days
干预措施: Udenafil (Drug)
Udenafil 87.5 mg BID
Udenafil 87.5 mg tablet twice daily for 5 days
干预措施: Udenafil (Drug)
Udenafil 125 mg QD
Udenafil 125 mg tablet once daily for 5 days
干预措施: Udenafil (Drug)
结局指标
主要结局
Number of Subjects With Serious Adverse Events Possibly or Probably Related to Udenafil
时间窗: 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.
次要结局
- 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)
- Evaluate the Pharmacokinetic (PK) Profile of Udenafil: AUC (0-tau)(Day 5, zero to 48 hours after the last dose)
- Evaluate the Pharmacokinetic (PK) Profile of Udenafil: CLSS/F(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)](Day 1 (baseline) and Day 5 (follow-up))
- Absolute Change in Blood Pool Myocardial Performance Index (MPI)(Day 1 (baseline) and Day 5 (follow-up))
- Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: Tmax(Day 5, zero to 48 hours after the last dose)
- Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: T-1/2(Day 5, zero to 48 hours after the last dose)
- Evaluate the Pharmacokinetic (PK) Profile of Metabolite DA-8164: AUC(0-tau)(Day 5, zero to 48 hours after the last dose)