A Single Center, Randomized, Open-label, Cross-over Exploratory Study to Evaluate the Pharmacodynamic and Pharmacokinetic Response to a Subcutaneous Administration or Oral Administration of Furosemide in Subjects With Heart Failure Presenting With Chronic Fluid Overload
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Diuresis and natriuresis
研究概览
简要总结
The purpose of this pilot study is to investigate the pharmacodynamic and pharmacokinetic parameters of a novel furosemide formulation administered subcutaneously as compared to oral furosemide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent obtained before any assessment is performed
- •Male and female subjects ≥18 years of age, with body weight <120 kg and body mass index (BMI) <30 kg/m2
- •Female subjects must be at least 2 years post-menopausal
- •Participant must have been on oral furosemide (40 mg oid or bid) or therapeutic equivalent (bumetanide 1 mg oid or bid) for a period 90 days before the first dose of study medication
- •History of chronic heart failure according to 2012 ESC guidelines with presence of moderate symptoms of chronic fluid overload. Chronic fluid overload is defined as presence of stable signs and symptoms of heart failure and congestion, like dyspnea at mild exertion or minimal exertion, pulmonary congestion and/or peripheral edema at the time of presentation in combination with elevated levels on natriuretic peptides (NT-proBNP > 300 ng/L)
- •In the opinion of the investigator, able to participate in the study
排除标准
- •Acute Decompensated Heart Failure (ADHF) or recent history of ADHF or significant worsening in their HF symptoms (within prior 2 weeks)
- •Contraindication to furosemide
- •Systolic BP (SBP) < 90 mm Hg
- •Temperature > 38°C (oral or equivalent) or sepsis or active infection requiring i.v. anti-microbial treatment
- •Serum sodium < 130 mmol/L and Serum potassium < 3.0 mmol/L
- •Current or planned (throughout the completion of study drug infusion) treatment with any i.v. therapies, including inotropic agents, vasopressors, levosimendan, nesiritide or analogues; or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device)
- •History of gastric or intestinal surgery that may affect absorption of oral medication
- •Presence or need for urinary catheterization
- •Current or planned ultrafiltration, hemofiltration, or dialysis
- •Impaired renal function defined as an estimated glomerular filtration rate (eGFR) on admission < 30 mL/min/1.73 m2 will be calculated as per standard at local laboratory
- •Administration of intravenous radiographic contrast agent within 72 hours prior to screening or acute contrast-induced nephropathy at the time of screening
- •Major surgery within 30 days prior to screening
- •Administration of an investigational drug or implantation of investigational device, or participation in another trial, within 30 days before screening
- •Inability to follow instructions or comply with procedures
- •Any surgical or medical condition which in the opinion of the investigator may interfere with participation in the study or which may affect the outcome of the study
研究组 & 干预措施
Group 1
Furosemide injection solution for subcutaneous administration (80 mg) over 5 hours followed by Oral Furosemide tablets (80 mg) in second period.
干预措施: Furosemide injection solution for subcutaneous administration (80 mg) (Drug)
Group 1
Furosemide injection solution for subcutaneous administration (80 mg) over 5 hours followed by Oral Furosemide tablets (80 mg) in second period.
干预措施: Oral Furosemide tablets (80 mg) (Drug)
Group 2
Oral Furosemide tablets (80 mg) followed by Furosemide injection solution for subcutaneous administration (80 mg) over 5 hours in second period.
干预措施: Furosemide injection solution for subcutaneous administration (80 mg) (Drug)
Group 2
Oral Furosemide tablets (80 mg) followed by Furosemide injection solution for subcutaneous administration (80 mg) over 5 hours in second period.
干预措施: Oral Furosemide tablets (80 mg) (Drug)
结局指标
主要结局
Diuresis and natriuresis
时间窗: 8 hours
Statistical summaries with a graphical presentation will show mean and individual diuresis and natriuresis time profiles such as time to first void, volume of first void, diuresis and natriuresis measured at 60 minute intervals up to 480 minutes following furosemide injection solution for subcutaneous administration or oral tablets. The diuretic response will be compared between therapies using t-tests or Wilcoxon test.
次要结局
- Body Water Content(8 hours)
- Pharmacokinetic profiles(8 hours)
- Cardiac Markers (NTpro-BNP, hs-Trop T, galectin-3)(8 hours)
- Dypsnea Scores on Visual Analog Scale and Likert Scale(8 hours)
- Injection site reaction on Draize Scale and Visual Analog Pain Scale(8 hours)