Clinical trial NCT03754660: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension, Pulmonary
Keywords: PAH
CTEPH
pulmonary arterial hypertension
chronic thromboembolic pulmonary hypertension
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-11-27
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: 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


Eligibility 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

Primary outcomes:
measure: Peak percent reduction in PVR (Pulmonary vascular resistance) from "baseline 2" for untreated patients
timeFrame: Up to 5 hours post inhalation of BAY1237592 compared to "baseline 2"
measure: Peak percent reduction in PVR from "baseline" for pre-treated patients
timeFrame: Up to 5 hours post inhalation of BAY1237592 compared to "baseline"
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 7 days after treatment
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 4
country: Czechia
facility: Institut Klinicke a Experimentalni Mediciny
city: München
country: Germany
facility: Krankenhaus Neuwittelsbach
state: Bayern
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
state: Bayern
city: Gießen
country: Germany
facility: Universitätsklinikum Giessen und Marburg
state: Hessen
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
state: Sachsen
city: Krakow
country: Poland
facility: Szpital Specjalistyczny im. Jana Pawla II
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: