A Non-randomized Two Part Multi-center, Open-label, Single Dose Trial With an Escalation Part in Untreated Pulmonary Arterial Hypertension (PAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Patients (Part A), Followed by a Parallel-group Part in Untreated and Pre-treated Patients With PAH and CTEPH (Part B) to Investigate the Safety, Tolerability and Pharmacodynamics of Inhaled BAY1237592
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 38
- 试验地点
- 8
- 主要终点
- Peak percent reduction in PVR (Pulmonary vascular resistance) from "baseline 2" for untreated patients
研究概览
简要总结
In this trial the effects of the inhaled drug BAY1237592 will be studied in patients with high blood pressure in the pulmonary blood vessels due to Pulmonary Arterial Hypertension (PAH) and due to Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Pulmonary hypertension is characterized by the elevation of pressure in the pulmonary arteries (PAP) and of the pulmonary vascular resistance (PVR) leading to increased workload of the right chamber of the heart to eject blood against this elevated resistance. The goal of this study is to measure the safety and tolerability of the drug as well as the reduction of the PVR at different doses
In Part A patients without specific treatment for PH (untreated patients) will be tested. In Part B also patients stably pre-treated with specific PH drugs will be studied in combination with the new inhaled drug
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with PAH or CTEPH undergoing medically indicated routine invasive diagnostics
- •Men and women aged 18 to 80 years
- •Untreated patients: Therapy-naïve patients (defined as off treatment with PDE-5 inhibitors, endothelin receptor antagonists, prostanoids, or other sGC stimulators/activators) with PAH or CTEPH or patients pre-treated with these medications who have to undergo a drug specific wash-out period at the discretion of the investigator for least 24 h prior to Day -1 if medically safe
- •Untreated patients with PAH or CTEPH:
- •- Group 1 (total will be summed up with corresponding dosage group from Part A)
- •Pre-treated patients with PAH or CTEPH:
- •Group 2: Pre-treated patients with any kind of monotherapy* for PAH/CTEPH
- •Group 3: Pre-treated patients with any kind of double combination therapy* for PAH/CTEPH * patients receiving inhaled Iloprost, and patients who are known responders to iNO are excluded
排除标准
- •Medical history indicating a different cause for PH than PAH or CTEPH according to the guidelines of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), such as significant left heart disease, valvular disease, or structural heart defects, as assessed by the investigator, significant pulmonary disease or clinical suspicion of pulmonary venoocclusive disease
研究组 & 干预措施
Untreated patients (Part A and Part B)
Part A: Untreated PAH and CTEPH patients will be enrolled to test 5 ascending doses of BAY1237592 with 4 patients per dose group up to a maximum dose of 4000 µg.
Part B: The highest safe, well tolerated and effective dose of Part A will be tested in further untreated patients.
干预措施: BAY1237592 (Drug)
Monotherapy (Part B)
The highest safe, well tolerated and effective dose chosen from Part A will be tested in pre-treated patients with any kind of monotherapy for PAH/CTEPH.
干预措施: BAY1237592 (Drug)
Combined therapy (Part B)
The highest safe, well tolerated and effective dose from Part A will be tested in pre-treated patients with any kind of double combination treatment for PAH/CTEPH.
干预措施: BAY1237592 (Drug)
结局指标
主要结局
Peak percent reduction in PVR (Pulmonary vascular resistance) from "baseline 2" for untreated patients
时间窗: Up to 5 hours post inhalation of BAY1237592 compared to "baseline 2"
PVR = 80\* (PAP - PCWP) / CO (dyn·sec·cm-5) * PAP = pulmonary arterial pressure * PCWP = pulmonary capillary wedge pressure * CO = cardiac output
Peak percent reduction in PVR from "baseline" for pre-treated patients
时间窗: Up to 5 hours post inhalation of BAY1237592 compared to "baseline"
PVR = 80\* (PAP - PCWP) / CO (dyn·sec·cm-5)
次要结局
- Incidence of treatment-emergent adverse events (TEAEs)(Up to 7 days after treatment)