Proof of Concept Study to Investigate Safety, Tolerability, Pharmacokinetics and the Impact on Pulmonary and Systemic Hemodynamics of a Single Oral Dose of BAY60-4552 in Patients With Biventricular Chronic Heart Failure and Pulmonary Hypertension in a Non-randomized, Non-blinded, Dose Escalation Design.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 55
- 主要终点
- AUC
研究概览
简要总结
This study is to demonstrate the safety and tolerability of a single oral dose of BAY60-4552 in a single dose escalation design. Furthermore, this study examines the changes in hemodynamics after application of the test substance.42 hospitalized stable patients with chronic heart failure will be included. Several measurements will be performed to test how good the drug works and wether there are any unwanted reactions to the drug (e.g. blood tests, ECG, heart rate, blood pressure, adverse events). After a observation period the patient will be discharged from the hospital.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with chronic heart failure, undergoing routine invasive measurement of hemodynamic parameters
排除标准
- •Acute heart failure or acute decompensated heart failure, need for acute cardiologic intervention or surgery, severe renal or hepatic insufficiency, severe valvular disease
研究组 & 干预措施
BAY60-4552, 1 mg
Subjects were planned to receive 1 mg of BAY60-4552 as solution
干预措施: BAY60-4552 (Drug)
BAY60-4552, 2.5 mg
Subjects were planned to receive 2.5 mg of BAY60-4552 as tablet
干预措施: BAY60-4552 (Drug)
BAY60-4552, 5 mg
Subjects were planned to receive 5.0 mg of BAY60-4552 as tablet
干预措施: BAY60-4552 (Drug)
BAY60-4552, 7.5 mg
Subjects were planned to receive 7.5 mg of BAY60-4552 as tablet
干预措施: BAY60-4552 (Drug)
BAY60-4552, 10 mg
Subjects were planned to receive 10 mg of BAY60-4552 as tablet
干预措施: BAY60-4552 (Drug)
结局指标
主要结局
AUC
时间窗: Pre-dose and up to 72 hr post-dose
Area under the plasma concentration vs time curve from zero to infinity after single dose
Number of participants with adverse events
时间窗: Approximately 2 weeks
Change in mean pulmonary artery pressure
时间窗: Pre-dose and up to 6 hr post-dose
Change in pulmonary capillary wedge pressure
时间窗: Pre-dose and up to 6 hr post-dose
AUC/D
时间窗: Pre-dose and up to 72 hr post-dose
AUC divided by dose (mg)
Cmax
时间窗: Pre-dose and up to 72 hr post-dose
Maximum drug concentration in plasma after single dose administration
Cmax/D
时间窗: Pre-dose and up to 72 hr post-dose
Cmax divided by dose (mg)
次要结局
- Systolic pulmonary artery pressure(Pre-dose and up to 6 hr post-dose)
- Pulmonary vascular resistance(Pre-dose and up to 6 hr post-dose)
- Pulmonary vascular resistance index(Pre-dose and up to 6 hr post-dose)
- Apparent volume of distribution associated with the terminal phase (after oral administration)(Pre-dose and up to 72 hr post-dose)
- Amount of drug excreted via urine(Pre-dose and up to 6 hr post-dose)
- Percent amount of drug excreted via urine(Pre-dose and up to 6 hr post-dose)
- Mean right atrial pressure(Pre-dose and up to 6 hr post-dose)
- Heart rate(At pre-study visit, pre-dose and up to 24 hr post-dose)
- Cardiac output(Pre-dose and up to 6 hr post-dose)
- Systemic vascular resistance(Pre-dose and up to 6 hr post-dose)
- Diastolic pulmonary artery pressure(Pre-dose and up to 6 hr post-dose)
- Cmax,norm(Pre-dose and up to 72 hr post-dose)
- tmax(Pre-dose and up to 72 hr post-dose)
- t½(Pre-dose and up to 72 hr post-dose)
- Mean residence time(Pre-dose and up to 72 hr post-dose)
- Total body clearance of drug from plasma calculated after oral administration (apparent oral clearance)(Pre-dose and up to 72 hr post-dose)
- AUC(0-tn)norm(Pre-dose and up to 72 hr post-dose)
- Systemic vascular resistance index(Pre-dose and up to 6 hr post-dose)
- Cardiac index(Pre-dose and up to 6 hr post-dose)
- Mean arterial pressure(Pre-dose and up to 6 hr post-dose)
- Systemic blood pressure(At pre-study visit, pre-dose and up to 24 hr post-dose)
- Diastolic blood pressure(At pre-study visit, pre-dose and up to 24 hr post-dose)
- Dyspnea Score(Pre-dose and up to 48 hr post-dose)
- AUC(0-6)(Pre-dose and up to 6 hr post-dose)
- AUCnorm(Pre-dose and up to 72 hr post-dose)
- AUC(0-tn)(Pre-dose and up to 72 hr post-dose)
- Renal clearance of drug(Pre-dose and up to 6 hr post-dose)
- Renin activity(Pre-dose and up to 24 hr post-dose)
- Change from baseline of noradrenaline after drug administration(Pre-dose and up to 24 hr post-dose)
- N-terminal pro-atrial natriuretic peptide(Pre-dose and up to 24 hr post-dose)
- NT-pro B-type natriuretic peptide(Pre-dose and up to 24 hr post-dose)
- Big endothelin-1(Pre-dose and up to 24 hr post-dose)
- Cystatin C(Pre-dose and up to 24 hr post-dose)
- Change from baseline of osteopontin after drug administration(Pre-dose and up to 24 hr post-dose)
- Cyclic guanosine mono-phosphate(Pre-dose and up to 24 hr post-dose)