Proof of Concept Study to Investigate Safety, Tolerability, Pharmacokinetics and the Impact on Pulmonary and Systemic Hemodynamics, Gas Exchange and Lung Function Parameters of a Single-dose of BAY63-2521 IR-tablet in Patients With COPD Associated Pulmonary Hypertension in an Non-randomized, Non-blinded Design
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 23
- 主要终点
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean)
研究概览
简要总结
This study is to demonstrate the safety, tolerability, pharmakokinetic and pharmacodynamic effect of a single oral dose of BAY63-2521 in patients with pulmonary hypertension due to chronic obstructive pulmonary disease (COPD).
详细描述
In addition to the pharmacodynamic and pharmacokinetic variables, the following laboratory variables were assessed:
- Hematology: Leucocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelets, white blood cell (WBC), partial thromboplastin time (PTT), prothrombin time (Quick), international normalized ratio (INR) (prothrombin time expressed in relation to normal value) ;
- Clinical chemistry: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transpeptidase (GGT), creatine phosphokinase (CK), lipase, cholinesterase (CHE), glucose, creatinine, urea, uric acid, bilirubin, total protein, serum albumin, sodium, potassium, calcium, chloride.
And due to the small number of subjects analyzed at several local labs, no summary statistics were provided.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 pulmonary hypertension due to COPD, undergoing routine invasive measurement of hemodynamic parameters.
- •Catheters for measurement of hemodynamic parameters (PAP [pulmonary artery pressure], PCWP [pulmonary capillary wedge pressure], CO [cardiac output], SBP [systolic blood pressure]) must be in place independent of the trial.
排除标准
- •Acute exacerbation of COPD,
- •Pre-existing lung disease other than COPD,
- •Acute or severe chronic left heart failure,
- •Severe coronary artery disease,
- •Uncontrolled arterial hypertension;
- •Severe left ventricular hypertrophy,
- •Congenital or acquired valvular or myocardial disease,
- •Systolic blood pressure < 100 mmHg,
- •Heart rate < 55 bpm or >105 bpm,
- •PaO2 (arterial partial oxygen pressure)/FiO2 (fraction of inspired oxygen) < 50 mmHg,
- •PaCO2 (arterial partial pressure of carbon dioxide) > 55 mmHg,
- •Severe hepatic insufficiency,
- •Severe renal insufficiency.
研究组 & 干预措施
Riociguat (Adempas, BAY63-2521) 1.0 mg
Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
干预措施: Riociguat (Adempas, BAY63-2521) 1.0 mg (Drug)
Riociguat (Adempas, BAY63-2521) 2.5 mg
Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
干预措施: Riociguat (Adempas, BAY63-2521) 2.5 mg (Drug)
结局指标
主要结局
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean)
时间窗: From baseline up to 4 hours after administration
PAPmean was reported during right heart catheterization
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance (PVR)
时间窗: From baseline up to 4 hours after administration
PVR was calculated according to the formula PVR = 80\*(PAPmean - pulmonary capillary wedge pressure)/cardiac output
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat
时间窗: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
时间窗: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose Per kg Body Weight (AUCnorm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
时间窗: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
时间窗: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
时间窗: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
时间窗: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
次要结局
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Arterial Pressure (MAP)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Right Atrial Pressure (RAPmean)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Pulmonary Artery Pressure (PAPsyst)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Pulmonary Artery Pressure (PAPdiast)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Capillary Wedge Pressure (PCWP)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Heart Rate (HR)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Blood Pressure (SBP)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Blood Pressure (DBP)(From baseline up to 4 hours after administration)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity (TLC)(Baseline and 2 hours post dose)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Output (CO)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance Index (PVRI)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance (SVR)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance Index (SVRI)(From baseline up to 4 hours after administration)
- Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Index(From baseline up to 4 hours after administration)
- Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Oxygen Pressure (PaO2)(Baseline and 2 hours post dose)
- Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Pressure of Carbon Dioxide (PaCO2)(Baseline and 2 hours post dose)
- Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Pressure (PvO2)(Baseline and 2 hours post dose)
- Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Oxygen Saturation (SaO2)(Baseline and 2 hours post dose)
- Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Saturation (SvO2)(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Expiratory Volume in 1 Second (FEV1)(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FEV1(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Vital Capacity (FVC)(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FVC(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of FEV1/FVC(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted TLC(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Residual Volume (RV)(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted RV(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 75% of Expiratory Vital Capacity (MEF75)(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 50% of Expiratory Vital Capacity (MEF50)(Baseline and 2 hours post dose)
- Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Dead Space Ventilation(Baseline and 1 hour post dose)
- Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Low V/Q Perfusion(Baseline and 1 hour post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Specific Diffusing Capacity(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 25% of Expiratory Vital Capacity (MEF25)(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Airway Resistance (Raw)(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Vital Capacity (VC)(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted VC(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)(Baseline and 2 hours post dose)
- Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity at the Time When the DLCO is Measured (Alveolar Volume, VA)(Baseline and 2 hours post dose)
- Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Ventilation (V)(Baseline and 1 hour post dose)
- Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Perfusion (Q)(Baseline and 1 hour post dose)
- Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Normal V/Q Perfusion(Baseline and 1 hour post dose)
- Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hours Post Dose of Ventilation-perfusion Distribution Presented as Standard Deviation (SD) of Perfusion(Baseline and 1 hour post dose)
- Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Ventilation-perfusion Distribution Presented as Standard Deviation (SD) of Ventilation(Baseline and 1 hour post dose)
- Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Intrapulmonary Shunt Flow(Baseline and 1 hour post dose)
- Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat(Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose)
- Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat(Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose)
- Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat(Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose)
- Area Under the Plasma Concentration Verse Time Curve From Zero to the Last Data Point (AUC0-tn) of Riociguat and Metabolite M1 After Single Dose of Riociguat(Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose)