This Study Tests the Safety of Inhaled BAY1237592, How the Drug is Tolerated and How it Effects Patients With High Blood Pressure in the Arteries of the Lungs in the Two Different Disease Groups Pulmonary Arterial Hypertension (PAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Drug: BAY1237592


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Patients with PAH or CTEPH undergoing medically indicated routine invasive diagnostics Men and women aged 18 to 80 years Part A: - 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 Part B: 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 Main Exclusion Criteria: - 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Untreated patients (Part A and Part B)<br>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. | Drug: BAY1237592<br>* Oral inhalation with dry powder inhaler, single dose.<br>|
| Experimental: Monotherapy (Part B)<br>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. | Drug: BAY1237592<br>* Oral inhalation with dry powder inhaler, single dose.<br>|
| Experimental: Combined therapy (Part B)<br>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. | Drug: BAY1237592<br>* Oral inhalation with dry powder inhaler, single dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak percent reduction in PVR (Pulmonary vascular resistance) from baseline 2 for untreated patients | PVR = 80* (PAP - PCWP) / CO (dyn·sec·cm-5) PAP = pulmonary arterial pressure PCWP = pulmonary capillary wedge pressure CO = cardiac output | Up to 5 hours post inhalation of BAY1237592 compared to baseline 2 | 
| Peak percent reduction in PVR from baseline for pre-treated patients | PVR = 80* (PAP - PCWP) / CO (dyn·sec·cm-5) | Up to 5 hours post inhalation of BAY1237592 compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) |  | Up to 7 days after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAH, CTEPH, pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension