<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/NCT03255512</url>
  </required_header>
  <id_info>
    <org_study_id>18582</org_study_id>
    <secondary_id>2016-005178-36</secondary_id>
    <nct_id>NCT03255512</nct_id>
  </id_info>
  <brief_title>Vericiguat Drug-drug Interaction Study With Isosorbite Mononitrate in Stable Coronary Artery Disease Patients</brief_title>
  <acronym>VISOR</acronym>
  <official_title>Multi-center, Randomized, Placebo-controlled, Double-blind Group Comparison Study to Investigate Safety, Tolerability and Blood Pressure of 2.5 mg, 5.0 mg and 10 mg Vericiguat Each Given Over 14 ± 3 Days Together With Isosorbite Mononitrate (ISMN) 60 mg Extended Release Formulation After a Pretreatment Phase (ISMN-starting Dose: 30 mg) in Stable Coronary Artery Disease (CAD) Patients With or Without Heart Failure Aged 30 to 80 Years - Vericiguat ISOsoRbite Mononitrate Interaction (VISOR) Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Bayer</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This study is intended to investigate the pharmacodynamic drug-drug interaction as well as&#xD;
      the safety and tolerability of isosorbite mononitrate and vericiguat in patients with stable&#xD;
      coronary artery disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 17, 2017</start_date>
  <completion_date type="Actual">March 23, 2018</completion_date>
  <primary_completion_date type="Actual">February 7, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>Regular measurements of blood pressure after a vericiguat administration on the first and on the last days of each dose step of vericiguat, and on the first days of ISMN up-titration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Heart rate</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>Regular measurements heart rate after a vericiguat administration on the first and on the last days of each dose step of vericiguat, and on the first days of ISMN up-titration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>Up to 9 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Vericiguat + isosorbite mononitrate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects received Isosorbide mononitrate (ISMN) up-titration with 30 mg / 60 mg, about 7 days each,prior to start of vericiguat administration.&#xD;
Then subjects received 2.5 mg vericiguat for about 14 days, followed by 5 mg vericiguat for about 14 days, followed by 10 mg vericiguat for about 14 days together 60 mg ISMN od on each day of vericiguat administration, taken 1 hour prior to vericiguat (in-house days) or together with vericiguat (out-patient days).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo + isosorbite mononitrate</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects received Isosorbide mononitrate (ISMN) up-titration with 30 mg / 60 mg, about 7 days each, prior to start of placebo administration.&#xD;
Then subjects received placebo matching 2.5 mg vericiguat for about 14 days, followed by placebo matching 5 mg vericiguat for about 14 days, followed by placebo matching 10 mg vericiguat for about 14 days together 60 mg ISMN od on each day of placebo administration, taken 1 hour prior to placebo (in-house days) or together with placebo (out-patient days).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vericiguat (BAY1021189)</intervention_name>
    <description>2.5 mg/tablet; 5 mg/tablet or 10 mg/tablet</description>
    <arm_group_label>Vericiguat + isosorbite mononitrate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo</description>
    <arm_group_label>Placebo + isosorbite mononitrate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isosorbide mononitrate (ISMN)</intervention_name>
    <description>30 mg/tablet or 60 mg/tablet</description>
    <arm_group_label>Placebo + isosorbite mononitrate</arm_group_label>
    <arm_group_label>Vericiguat + isosorbite mononitrate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients with stable CAD defined by&#xD;
&#xD;
          -  coronary artery stenosis in any of the 3 main coronary vessels &gt; 50% documented by&#xD;
             coronary angiography within last 36 months&#xD;
&#xD;
          -  or history of myocardial infarction&#xD;
&#xD;
          -  Age: 30 to 80 years (inclusive) at the first screening examination&#xD;
&#xD;
          -  Body mass index (BMI): above/equal 18.0 and below/equal 36.0 kg / m²&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Intervention e.g. revascularization by percutaneous coronary intervention (PCI) and/or&#xD;
             coronary artery bypass graft (CABG) during the last 3 months&#xD;
&#xD;
          -  Progressive angina with symptoms of worsening of angina within the &lt; 3 months prior to&#xD;
             the first screening examination&#xD;
&#xD;
          -  History of recent (&lt; 6 months prior to the first screening examination) myocardial&#xD;
             infarction or unstable angina&#xD;
&#xD;
          -  Symptomatic carotid stenosis, or transient ischemic attack or stroke within 3 months&#xD;
             prior to the first screening examination or patients with stroke at more than 3 months&#xD;
             prior to the first screening examination with significant residual neurologic&#xD;
             involvement&#xD;
&#xD;
          -  Insulin dependent diabetes mellitus&#xD;
&#xD;
          -  Clinically relevant cardiac ischemia at screening&#xD;
&#xD;
          -  Clinical significant persistent ischemia, which should be ruled out by clinical&#xD;
             judgment of the investigator, based on medical history, available clinical data e.g.&#xD;
             past angiograms or preexisting or current exercise testing with any imaging technique&#xD;
             (e.g. dobutamine stress echocardiography, adenosine or dobutamine stress cardiac&#xD;
             magnetic resonance imaging (CMR), scinthigraphy or exercise ECG)&#xD;
&#xD;
          -  Atrial fibrillation, pacemaker, defibrillator, atrial ventricular (AV)-block II and&#xD;
             III&#xD;
&#xD;
          -  Systolic blood pressure below 110 or above 160 mmHg at first screening visit&#xD;
&#xD;
          -  Diastolic blood pressure above 100 mmHg at first screening visit&#xD;
&#xD;
          -  Heart rate below 50 or above 100 beats / min (taken from ECG measurement) at first&#xD;
             screening visit&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) &lt; 30 mL/min/1.73m*2 at first screening&#xD;
             visit&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 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>Universitätsherzzentrum Freiburg - Bad Krozingen</name>
      <address>
        <city>Bad Krozingen</city>
        <state>Baden-Württemberg</state>
        <zip>79189</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <state>Baden-Württemberg</state>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Einrichtungen der Universität Bonn</name>
      <address>
        <city>Bonn</city>
        <state>Nordrhein-Westfalen</state>
        <zip>53105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SocraTec R&amp;D GmbH</name>
      <address>
        <city>Erfurt</city>
        <state>Thüringen</state>
        <zip>99084</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité - Campus Virchow-Klinikum (CVK)</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Hamburg Eppendorf (UKE)</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://clinicaltrials.bayer.com/</url>
    <description>Click here to find results for studies related to Bayer products.</description>
  </link>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>December 9, 2021</last_update_submitted>
  <last_update_submitted_qc>December 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Isosorbide</mesh_term>
    <mesh_term>Isosorbide Dinitrate</mesh_term>
    <mesh_term>Isosorbide-5-mononitrate</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03255512
org study id: 18582
secondary id: 2016-005178-36
nct id: NCT03255512
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is intended to investigate the pharmacodynamic drug-drug interaction as well as
      the safety and tolerability of isosorbite mononitrate and vericiguat in patients with stable
      coronary artery disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Blood pressure
time frame: Up to 8 weeks
description: Regular measurements of blood pressure after a vericiguat administration on the first and on the last days of each dose step of vericiguat, and on the first days of ISMN up-titration.
measure: Heart rate
time frame: Up to 8 weeks
description: Regular measurements heart rate after a vericiguat administration on the first and on the last days of each dose step of vericiguat, and on the first days of ISMN up-titration.
measure: Number of participants with adverse events
time frame: Up to 9 weeks
arm group label: Vericiguat + isosorbite mononitrate
arm group type: Experimental
description: Subjects received Isosorbide mononitrate (ISMN) up-titration with 30 mg / 60 mg, about 7 days each,prior to start of vericiguat administration.
Then subjects received 2.5 mg vericiguat for about 14 days, followed by 5 mg vericiguat for about 14 days, followed by 10 mg vericiguat for about 14 days together 60 mg ISMN od on each day of vericiguat administration, taken 1 hour prior to vericiguat (in-house days) or together with vericiguat (out-patient days).
arm group label: Placebo + isosorbite mononitrate
arm group type: Placebo Comparator
description: Subjects received Isosorbide mononitrate (ISMN) up-titration with 30 mg / 60 mg, about 7 days each, prior to start of placebo administration.
Then subjects received placebo matching 2.5 mg vericiguat for about 14 days, followed by placebo matching 5 mg vericiguat for about 14 days, followed by placebo matching 10 mg vericiguat for about 14 days together 60 mg ISMN od on each day of placebo administration, taken 1 hour prior to placebo (in-house days) or together with placebo (out-patient days).
intervention type: Drug
intervention name: Vericiguat (BAY1021189)
description: 2.5 mg/tablet; 5 mg/tablet or 10 mg/tablet
arm group label: Vericiguat + isosorbite mononitrate
intervention type: Drug
intervention name: Placebo
description: Matching placebo
arm group label: Placebo + isosorbite mononitrate
intervention type: Drug
intervention name: Isosorbide mononitrate (ISMN)
description: 30 mg/tablet or 60 mg/tablet
arm group label: Placebo + isosorbite mononitrate
arm group label: Vericiguat + isosorbite mononitrate
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: No
last name: Bayer Study Director
role: Study Director
affiliation: Bayer
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
url: http://clinicaltrials.bayer.com/
description: Click here to find results for studies related to Bayer products.
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Isosorbide
mesh term: Isosorbide Dinitrate
mesh term: Isosorbide-5-mononitrate