A Multi-Center, Unblinded, Single-Arm Study to Evaluate Sex Differences in the Acute Effects of PL-3994 on Myocardial cGMP Enhancement and Hemodynamics in Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Part B: Coronary Sinus Levels
研究概览
简要总结
A Multi-Center, Unblinded, Single-Arm Study to Evaluate Sex Differences in the Acute Effects of PL-3994 on Myocardial cGMP Enhancement and Hemodynamics in Heart Failure with Preserved Ejection Fraction
详细描述
Multi-center, unblinded, dose ascending, two-part pilot study involving Part A, up to 15 subjects for dose ascension and optimization (N=3 per dose level, up to 5 dose levels) and Part B, 40 patients (n=20 women, n=20 men), with a single dose of PL-3994 after which hemodynamics will be measured by pulmonary artery catheter and pulmonary artery (mixed venous) and coronary sinus blood sampling will be performed to measure cGMP levels during a 15-minute observation period.
The objective of this study is to evaluate the acute effects of a single dose of intravenous PL-3994 on hemodynamics and myocardial cGMP expression.
The following endpoints will be assessed:
- Hemodynamics (including blood pressure, right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output)
- Myocardial cGMP expression via coronary sinus sampling
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject has provided written informed consent.
- •Pre- or post-menopausal female or male age > 21 years
- •LVEF ≥ 45% by echocardiography within prior 6 months
- •Symptoms of HF requiring treatment with diuretics for ≥ 30 days prior to enrollment
- •Current symptoms of HF (NYHA class II-IV) at time of enrollment
- •6. The subject has clinical indication for right heart catheterization for evaluation of HFpEF
- •Negative pregnancy test in a female of childbearing potential
排除标准
- •A subject who meets ANY of the following exclusion criteria must not be enrolled.
- •Orthostatic hypotension, systolic blood pressure <100 mm Hg, diastolic blood pressure < 50 mmHg.
- •Any prior echocardiogram with LVEF < 40%
- •Hemoglobin < 9 g/dl
- •eGFR < 30 mL/min/1.73 m2
- •Hemodynamically significant arrhythmias within prior 4 weeks
- •Acute coronary syndrome, cardiac surgery, or percutaneous coronary intervention within prior 3 months
- •Any of the following cardiac diagnoses: active myocarditis, hypertrophic cardiomyopathy, > moderate regurgitant valvular disease, any valvular stenosis, restrictive cardiomyopathy (including amyloid, sarcoid, or hemochromatosis), constrictive pericarditis, complex congenital heart disease, or pulmonary arterial hypertension
- •Current need for IV inotropic medication
- •Currently taking nitrates or having stopped nitrates within 24 hours of visit
- •Currently taking antihistamines, antipsychotics, tri-cyclic antidepressants, catecholamines/related compounds, monoamine oxidase inhibitors, stimulants (including caffeine and nicotine), sympathomimetics, dopamine agonists. Additionally, medications that inhibit PDE activity will be prohibited during the study and for 5 half- lives prior to Day 1 so that cGMP measurements will not be affected
- •Currently hospitalized for HF
- •Any prior need for mechanical circulatory support
- •Previous adverse reaction to the study drug
- •Inability to comply with planned study procedures
- •Pregnant or nursing mothers
- •Participation in another study with an investigational drug or device within 30 days or a biologic study within 90 days prior to signing consent.
- •Study participants must use method of birth control that has been approved by the Study Doctor and males must not donate sperm during the study and for 30 days after the last dose of study drug.
研究组 & 干预措施
Part A: PL-3994 Dose Ascension
Dose ascension: up to 15 subjects with HFpEF. N = 3 per dose level, up to 5 dose levels.
干预措施: PL-3994 Aqueous Intravenous Solution Dose Ascention (Drug)
Part B: PL-3994 Single Dose
Up to 40 subjects with HFpEF (20 Females, 20 Males) will receive a single dose of PL-3994.
干预措施: PL-3994 Aqueous Intravenous Solution Single Dose (Drug)
结局指标
主要结局
Part B: Coronary Sinus Levels
时间窗: 1 day
Coronary sinus levels of cGMP post PL-3994 infusion as compared to baseline.
Part A: Dose Ascension
时间窗: 1 day
Reaching the maximum tolderated dose (MTD) as defined by meeting stopping criteria.
次要结局
- Part B: Pulmonary artery pressure measured in mmHg(1 day)
- Part B: Pulmonary capillary wedge pressure measured in mmHg(1 day)
- Part B: Cardiac output measured in L/min.(1 day)
- Part B: Blood pressure measured in mmHg(1 day)
- Part B: Heart rate measured in beats per minute(1 day)
- Part B: Right atrial pressure measured in mmHg(1 day)