Back to resultsThis 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)
Primary Purpose
Hypertension, Pulmonary
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BAY1237592
Sponsored by
About this trial
This is an interventional basic science trial for Hypertension, Pulmonary focused on measuring PAH, CTEPH, pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension
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
Sites / Locations
- Medizinische Universität Graz
- Vseobecna fakultni nemocnice v Praze
- Institut Klinicke a Experimentalni Mediciny
- Krankenhaus Neuwittelsbach
- Universitätsklinikum Regensburg
- Universitätsklinikum Giessen und Marburg
- Universitätsklinikum Carl Gustav Carus Dresden
- Szpital Specjalistyczny im. Jana Pawla II
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Untreated patients (Part A and Part B)
Monotherapy (Part B)
Combined therapy (Part B)
Arm 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.
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.
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.
Outcomes
Primary Outcome Measures
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
Peak percent reduction in PVR from "baseline" for pre-treated patients
PVR = 80* (PAP - PCWP) / CO (dyn·sec·cm-5)
Secondary Outcome Measures
Incidence of treatment-emergent adverse events (TEAEs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03754660
Brief Title
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)
Acronym
ATMOS
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
January 21, 2019 (Actual)
Primary Completion Date
April 24, 2022 (Actual)
Study Completion Date
November 3, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Pulmonary
Keywords
PAH, CTEPH, pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Untreated patients (Part A and Part B)
Arm Type
Experimental
Arm 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.
Arm Title
Monotherapy (Part B)
Arm Type
Experimental
Arm 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.
Arm Title
Combined therapy (Part B)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
BAY1237592
Intervention Description
Oral inhalation with dry powder inhaler, single dose.
Primary Outcome Measure Information:
Title
Peak percent reduction in PVR (Pulmonary vascular resistance) from "baseline 2" for untreated patients
Description
PVR = 80* (PAP - PCWP) / CO (dyn·sec·cm-5)
PAP = pulmonary arterial pressure
PCWP = pulmonary capillary wedge pressure
CO = cardiac output
Time Frame
Up to 5 hours post inhalation of BAY1237592 compared to "baseline 2"
Title
Peak percent reduction in PVR from "baseline" for pre-treated patients
Description
PVR = 80* (PAP - PCWP) / CO (dyn·sec·cm-5)
Time Frame
Up to 5 hours post inhalation of BAY1237592 compared to "baseline"
Secondary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events (TEAEs)
Time Frame
Up to 7 days after treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
Facility Name
Medizinische Universität Graz
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Vseobecna fakultni nemocnice v Praze
City
Praha 2
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Institut Klinicke a Experimentalni Mediciny
City
Praha 4
ZIP/Postal Code
140 21
Country
Czechia
Facility Name
Krankenhaus Neuwittelsbach
City
München
State/Province
Bayern
ZIP/Postal Code
80639
Country
Germany
Facility Name
Universitätsklinikum Regensburg
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
93053
Country
Germany
Facility Name
Universitätsklinikum Giessen und Marburg
City
Gießen
State/Province
Hessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus Dresden
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
Facility Name
Szpital Specjalistyczny im. Jana Pawla II
City
Krakow
ZIP/Postal Code
31-202
Country
Poland
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.
As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.
Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.
Links:
URL
http://www.clinicaltrialsregister.eu/
Description
Click here to find information about studies related to Bayer Healthcare products conducted in Europe
Learn more about this trial
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)
We'll reach out to this number within 24 hrs