A Single-blind, Multiple Dose, Placebo-controlled, Double Dummy Study to Investigate the Pharmacodynamic and Pharmacokinetic Interaction Between Aliskiren and Furosemide in Patients With Heart Failure
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Diuretic Efficacy Index 1 for Sodium Excretion
研究概览
简要总结
This study assessed the interaction between single and multiple doses of aliskiren (150 mg and 300 mg) and furosemide (60 mg) in patients with heart failure.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Systolic or diastolic heart failure, diagnosed with either NYHA functional class II to III at least 3 months prior to screening and on stable medication for at least 12 weeks.
- •Patients must have met either of the criteria at screening:
- •Documented left ventricular ejection fraction (LVEF) greater than 20% but lower than 40% OR
- •Patients with a documented LVEF greater than 40% and with a history of NT-pro-BNP> 400pg/mL (or BNP > 100pg/mL) within 12 months of screening.
排除标准
- •Treatment with Angiotensin Receptor Blockers (ARBs), aldosterone receptor antagonists and diuretics (other than furosemide) within 3 weeks of first dose and during the study. Beta blockers were permitted provided the dose was stable for at least 3 weeks before the first dose and remains so throughout the study.
- •Hypertrophic cardiomyopathy (HCMP).
- •If a subject is currently treated with furosemide, the dose must be stable for at least 3 weeks before the first dose and the dose must not exceed 60 mg daily
- •Stable heart failure requiring treatment with both an ACE inhibitor and an ARB or Current acute decompensated heart failure.
- •Mean sitting systolic blood pressure ≥160 mmHg and/or mean sitting diastolic blood pressure ≥ 100mmHg and/or secondary forms of hypertension.
- •Persistent sitting systolic blood pressure <90 mmHg.
- •History of angioedema.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Furosemide 60 mg + Aliskiren 150 mg
Treatment Period 2 (Day 8 to day 17): Patients received 60 mg furosemide, 150 mg aliskiren and 300 mg placebo once daily.
干预措施: Aliskiren 150 mg (Drug)
Furosemide 60 mg + Aliskiren 150 mg
Treatment Period 2 (Day 8 to day 17): Patients received 60 mg furosemide, 150 mg aliskiren and 300 mg placebo once daily.
干预措施: Furosemide 60 mg (Drug)
Furosemide 60 mg
Treatment period 1 (Day 1 to Day 7): All eligible patients received 60 mg furosemide, 150 mg placebo of aliskiren, and 300 mg placebo aliskiren once daily.
干预措施: Furosemide 60 mg (Drug)
Furosemide 60 mg
Treatment period 1 (Day 1 to Day 7): All eligible patients received 60 mg furosemide, 150 mg placebo of aliskiren, and 300 mg placebo aliskiren once daily.
干预措施: Placebo for Aliskiren (Drug)
Furosemide 60 mg + Aliskiren 150 mg
Treatment Period 2 (Day 8 to day 17): Patients received 60 mg furosemide, 150 mg aliskiren and 300 mg placebo once daily.
干预措施: Placebo for Aliskiren (Drug)
Furosemide 60 mg + Aliskiren 300 mg
Treatment Period 3 (Day 18 to day 27): Patients received 60 mg furosemide, 300 mg aliskiren and 150 mg placebo of aliskiren once daily.
干预措施: Furosemide 60 mg (Drug)
Furosemide 60 mg + Aliskiren 300 mg
Treatment Period 3 (Day 18 to day 27): Patients received 60 mg furosemide, 300 mg aliskiren and 150 mg placebo of aliskiren once daily.
干预措施: Placebo for Aliskiren (Drug)
Furosemide 60 mg + Aliskiren 300 mg
Treatment Period 3 (Day 18 to day 27): Patients received 60 mg furosemide, 300 mg aliskiren and 150 mg placebo of aliskiren once daily.
干预措施: Aliskiren 300 mg (Drug)
结局指标
主要结局
Diuretic Efficacy Index 1 for Sodium Excretion
时间窗: 0 to 24 hours
Efficacy of furosemide for sodium excretion (efficacy index 1) was defined by dividing urinary sodium excretion by the urinary excretion of furosemide. Diuretic index 1 for sodium was calculated for the for the total 0 to 24 hour urine collection.
Diuretic Efficacy Index 2 for Water Excretion
时间窗: 0 to 24 hours
Efficacy of furosemide for water excretion (efficacy index 2) was defined by dividing urine volume by the urinary excretion of furosemide.Diuretic index 2 for water was calculated for the 0 to 4 hour fraction and for the total 0 to 24 hour urine collection.
次要结局
- Plasma Pharmacokinetics (PK) of Furosemide: Area Under the Plasma Concentration-time Curve (AUC)(pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose)
- Urine Pharmacokinetics (PK) of Furosemide: Renal Clearance (CLR)(0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose)
- Plasma Pharmacokinetics (PK) of Furosemide: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax, ss)(pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose)
- Plasma Pharmacokinetics (PK) of Furosemide: Time to Reach the Maximum Concentration After Drug Administration (Tmax)(pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose)
- Plasma Pharmacokinetics (PK) of Furosemide: Average Steady State Plasma Concentration During Multiple Dosing (Cav,ss)(pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post dose)
- Plasma Pharmacokinetics (PK) of Furosemide: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin, ss)(pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24 hours post dose)
- Urine Pharmacokinetics (PK) of Furosemide: Amount of Drug Excreted Into the Urine From Time Zero to 24 Hours After Administration (Ae0-24)(0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose)
- Creatinine Clearance(0 to 4, 4 to 8, 8 to 12 and 12 to 24 hours post dose)
- Urine Sodium and Potassium Excretion Per Treatment at 4 Hours Postdose(4 hours postdose)
- Urine Sodium and Potassium Excretion Per Treatment at 8 Hours Postdose(8 hours postdose)
- Urine Sodium and Potassium Excretion Per Treatment at 12 Hours Postdose(12 hours postdose)
- Urine Sodium and Potassium Excretion Per Treatment at 24 Hours Postdose(24 hours postdose)
- Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP)(0.5 hour pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose.)