<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03754660</url>
  </required_header>
  <id_info>
    <org_study_id>17293</org_study_id>
    <secondary_id>2018-001791-37</secondary_id>
    <nct_id>NCT03754660</nct_id>
  </id_info>
  <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)</brief_title>
  <acronym>ATMOS</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bayer</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this trial the effects of the inhaled drug BAY1237592 will be studied in patients with&#xD;
      high blood pressure in the pulmonary blood vessels due to Pulmonary Arterial Hypertension&#xD;
      (PAH) and due to Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Pulmonary&#xD;
      hypertension is characterized by the elevation of pressure in the pulmonary arteries (PAP)&#xD;
      and of the pulmonary vascular resistance (PVR) leading to increased workload of the right&#xD;
      chamber of the heart to eject blood against this elevated resistance. The goal of this study&#xD;
      is to measure the safety and tolerability of the drug as well as the reduction of the PVR at&#xD;
      different doses&#xD;
&#xD;
      In Part A patients without specific treatment for PH (untreated patients) will be tested. In&#xD;
      Part B also patients stably pre-treated with specific PH drugs will be studied in combination&#xD;
      with the new inhaled drug&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 21, 2019</start_date>
  <completion_date type="Actual">November 3, 2022</completion_date>
  <primary_completion_date type="Actual">April 24, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Peak percent reduction in PVR (Pulmonary vascular resistance) from &quot;baseline 2&quot; for untreated patients</measure>
    <time_frame>Up to 5 hours post inhalation of BAY1237592 compared to &quot;baseline 2&quot;</time_frame>
    <description>PVR = 80* (PAP - PCWP) / CO (dyn·sec·cm-5)&#xD;
PAP = pulmonary arterial pressure&#xD;
PCWP = pulmonary capillary wedge pressure&#xD;
CO = cardiac output</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak percent reduction in PVR from &quot;baseline&quot; for pre-treated patients</measure>
    <time_frame>Up to 5 hours post inhalation of BAY1237592 compared to &quot;baseline&quot;</time_frame>
    <description>PVR = 80* (PAP - PCWP) / CO (dyn·sec·cm-5)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-emergent adverse events (TEAEs)</measure>
    <time_frame>Up to 7 days after treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Hypertension, Pulmonary</condition>
  <arm_group>
    <arm_group_label>Untreated patients (Part A and Part B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.&#xD;
Part B: The highest safe, well tolerated and effective dose of Part A will be tested in further untreated patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Monotherapy (Part B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combined therapy (Part B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BAY1237592</intervention_name>
    <description>Oral inhalation with dry powder inhaler, single dose.</description>
    <arm_group_label>Combined therapy (Part B)</arm_group_label>
    <arm_group_label>Monotherapy (Part B)</arm_group_label>
    <arm_group_label>Untreated patients (Part A and Part B)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          -  Patients with PAH or CTEPH undergoing medically indicated routine invasive diagnostics&#xD;
&#xD;
          -  Men and women aged 18 to 80 years&#xD;
&#xD;
        Part A:&#xD;
&#xD;
        - Untreated patients: Therapy-naïve patients (defined as off treatment with PDE-5&#xD;
        inhibitors, endothelin receptor antagonists, prostanoids, or other sGC&#xD;
        stimulators/activators) with PAH or CTEPH or patients pre-treated with these medications&#xD;
        who have to undergo a drug specific wash-out period at the discretion of the investigator&#xD;
        for least 24 h prior to Day -1 if medically safe&#xD;
&#xD;
        Part B:&#xD;
&#xD;
          -  Untreated patients with PAH or CTEPH:&#xD;
&#xD;
             -- Group 1 (total will be summed up with corresponding dosage group from Part A)&#xD;
&#xD;
          -  Pre-treated patients with PAH or CTEPH:&#xD;
&#xD;
               -  Group 2: Pre-treated patients with any kind of monotherapy* for PAH/CTEPH&#xD;
&#xD;
               -  Group 3: Pre-treated patients with any kind of double combination therapy* for&#xD;
                  PAH/CTEPH * patients receiving inhaled Iloprost, and patients who are known&#xD;
                  responders to iNO are excluded&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
        - Medical history indicating a different cause for PH than PAH or CTEPH according to the&#xD;
        guidelines of the European Society of Cardiology (ESC) and the European Respiratory Society&#xD;
        (ERS), such as significant left heart disease, valvular disease, or structural heart&#xD;
        defects, as assessed by the investigator, significant pulmonary disease or clinical&#xD;
        suspicion of pulmonary venoocclusive disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bayer Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Bayer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medizinische Universität Graz</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vseobecna fakultni nemocnice v Praze</name>
      <address>
        <city>Praha 2</city>
        <zip>128 08</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Klinicke a Experimentalni Mediciny</name>
      <address>
        <city>Praha 4</city>
        <zip>140 21</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krankenhaus Neuwittelsbach</name>
      <address>
        <city>München</city>
        <state>Bayern</state>
        <zip>80639</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Regensburg</name>
      <address>
        <city>Regensburg</city>
        <state>Bayern</state>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Giessen und Marburg</name>
      <address>
        <city>Gießen</city>
        <state>Hessen</state>
        <zip>35392</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Carl Gustav Carus Dresden</name>
      <address>
        <city>Dresden</city>
        <state>Sachsen</state>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Specjalistyczny im. Jana Pawla II</name>
      <address>
        <city>Krakow</city>
        <zip>31-202</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Czechia</country>
    <country>Germany</country>
    <country>Poland</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>November 23, 2018</study_first_submitted>
  <study_first_submitted_qc>November 23, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>November 7, 2022</last_update_submitted>
  <last_update_submitted_qc>November 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PAH</keyword>
  <keyword>CTEPH</keyword>
  <keyword>pulmonary arterial hypertension</keyword>
  <keyword>chronic thromboembolic pulmonary hypertension</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA &quot;Principles for responsible clinical trial data sharing&quot;. This pertains to scope, timepoint and process of data access.&#xD;
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.&#xD;
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.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03754660
org study id: 17293
secondary id: 2018-001791-37
nct id: NCT03754660
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Peak percent reduction in PVR (Pulmonary vascular resistance) from "baseline 2" for untreated patients
time frame: Up to 5 hours post inhalation of BAY1237592 compared to "baseline 2"
description: PVR = 80* (PAP - PCWP) / CO (dyn·sec·cm-5)
PAP = pulmonary arterial pressure
PCWP = pulmonary capillary wedge pressure
CO = cardiac output
measure: Peak percent reduction in PVR from "baseline" for pre-treated patients
time frame: Up to 5 hours post inhalation of BAY1237592 compared to "baseline"
description: PVR = 80* (PAP - PCWP) / CO (dyn·sec·cm-5)
measure: Incidence of treatment-emergent adverse events (TEAEs)
time frame: Up to 7 days after treatment
arm group label: Untreated patients (Part A and Part B)
arm group type: Experimental
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 group label: Monotherapy (Part B)
arm group type: Experimental
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 group label: Combined therapy (Part B)
arm group type: Experimental
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: BAY1237592
description: Oral inhalation with dry powder inhaler, single dose.
arm group label: Combined therapy (Part B)
arm group label: Monotherapy (Part B)
arm group label: Untreated patients (Part A and Part B)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Bayer Study Director
role: Study Director
affiliation: Bayer
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Czechia
country: Germany
country: Poland
responsible party type: Sponsor
mesh term: Hypertension, Pulmonary
mesh term: Pulmonary Arterial Hypertension
mesh term: Hypertension
sharing ipd: No
ipd 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.