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) (ATMOS)

Bayer

Status and phase: Completed; Phase 1

Conditions: Hypertension, Pulmonary

Treatments: Drug: BAY1237592

Study type: Interventional

Funder types: Industry

Identifiers

NCT03754660

2018-001791-37 (EudraCT Number)

17293

Details and patient eligibility

About

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

Enrollment: 38 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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38 participants in 3 patient groups

Untreated patients (Part A and Part B)

Experimental group

Description:

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.

Treatment:

Drug: BAY1237592

Monotherapy (Part B)

Experimental group

Description:

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.

Treatment:

Drug: BAY1237592

Combined therapy (Part B)

Experimental group

Description:

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.

Treatment:

Drug: BAY1237592