<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/NCT04454424</url>
  </required_header>
  <id_info>
    <org_study_id>20331</org_study_id>
    <nct_id>NCT04454424</nct_id>
  </id_info>
  <brief_title>Study on the Safety of BAY1817080, How it is Tolerated and the Way the Body Absorbs, Distributes and Gets Rid of the Study Drug in Participants With Impaired Liver Function or Normal Liver Function</brief_title>
  <official_title>An Open-label Study to Evaluate the Pharmacokinetics, Safety and Tolerability of BAY 1817080 in Participants With Impaired Hepatic Function (Classified as Child-Pugh A, B or C) in Comparison to Matched Controls With Normal Hepatic Function</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>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      BAY1817080 is currently under clinical development to treat pain related to unexplained&#xD;
      chronic cough or chronic cough not affected by a treatment (refractory and/or unexplained&#xD;
      chronic cough, RUCC), or a condition where the bladder is unable to hold urine normally&#xD;
      (overactive bladder, OAB) or a condition in which tissue similar to the tissue that normally&#xD;
      lines the inside of the womb grows outside the womb (endometriosis).&#xD;
&#xD;
      In this study researchers want to learn more about the safety of BAY1817080, how it is&#xD;
      tolerated and the way the body absorbs, distributes and gets rid of the study dug given as&#xD;
      tablet in participants with mild, moderate or severe hepatic impairment and participants with&#xD;
      normal liver function matched for age-, gender-, weight and race.&#xD;
&#xD;
      The study will enroll 36 male and female participants in the age between 18 and 79 years.&#xD;
      Participants with mild or moderate hepatic impairment and the matching participants will take&#xD;
      multiple oral doses of study drug depending on the study plan. Participants with severe&#xD;
      hepatic impairment and the matching participants will take a single oral dose of study drug&#xD;
      during the study. Data from this study will provide researcher important information for&#xD;
      further development of the study drug in particular on dose recommendation for patients with&#xD;
      hepatic impairment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 23, 2020</start_date>
  <completion_date type="Actual">December 15, 2021</completion_date>
  <primary_completion_date type="Actual">June 24, 2021</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>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUCu after single dose of BAY1817080</measure>
    <time_frame>On day 1</time_frame>
    <description>AUCu: Area under the Curve unbound</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax,u after single dose of BAY1817080</measure>
    <time_frame>On day 1</time_frame>
    <description>Cmax,u: maximum observed drug concentration in measured matrix after single dose administration (unbound)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with treatment-emergent adverse events</measure>
    <time_frame>from dosing up to 14 days after end of treatment with study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC (0-12)md,u after multiple dose of BAY1817080</measure>
    <time_frame>From day 6 to day 13</time_frame>
    <description>AUC (0-12)md,u: Area Under the Curve from 0-12 hours at steady state for the multiple dose (unbound)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax,md,u after multiple dose of BAY1817080</measure>
    <time_frame>From day 6 to day 13</time_frame>
    <description>Cmax,md,u: Maximum observed drug concentration at steady state for multiple dose (unbound)</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Endometriosis Related Pain</condition>
  <condition>Overactive Bladder</condition>
  <condition>Diabetic Neuropathic Pain</condition>
  <condition>Refractory or Unexplained Chronic Cough</condition>
  <arm_group>
    <arm_group_label>Arm A: Child-Pugh A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with mildly impaired hepatic function (Child-Pugh A)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: Child-Pugh B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with moderately impaired hepatic function (Child-Pugh B)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C: Child-Pugh C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with severely impaired hepatic function (Child-Pugh C)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm D: Normal hepatic (Matched A and B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with normal hepatic function matched to Arm A and B</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm E: Normal hepatic (Matched to C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with normal hepatic function matched to Arm C</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BAY1817080</intervention_name>
    <description>Study intervention BAY1817080 will be administered orally with tablet(s).</description>
    <arm_group_label>Arm A: Child-Pugh A</arm_group_label>
    <arm_group_label>Arm B: Child-Pugh B</arm_group_label>
    <arm_group_label>Arm C: Child-Pugh C</arm_group_label>
    <arm_group_label>Arm D: Normal hepatic (Matched A and B)</arm_group_label>
    <arm_group_label>Arm E: Normal hepatic (Matched to C)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>Midazolam will be administered intravenously with dose of 0.1 mg on Day 1.</description>
    <arm_group_label>Arm A: Child-Pugh A</arm_group_label>
    <arm_group_label>Arm B: Child-Pugh B</arm_group_label>
    <arm_group_label>Arm C: Child-Pugh C</arm_group_label>
    <arm_group_label>Arm D: Normal hepatic (Matched A and B)</arm_group_label>
    <arm_group_label>Arm E: Normal hepatic (Matched to C)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant must be 18 to 79 years of age inclusive, at the time of signing the&#xD;
             informed consent.&#xD;
&#xD;
          -  Participants with a medical history of chronic (For Hepatically Impaired Participants&#xD;
             only):&#xD;
&#xD;
               -  documented liver cirrhosis confirmed by histopathology, laparoscopy, fibroscan,&#xD;
                  CT, MRI or ultrasound, AND&#xD;
&#xD;
               -  hepatic impairment (Child-Pugh A or B or C), AND&#xD;
&#xD;
               -  stable liver disease, i.e. same Child-Pugh class for at least 2 months prior to&#xD;
                  screening.&#xD;
&#xD;
          -  Body mass index (BMI) within the range 18 to 38 kg/m^2 (both inclusive).&#xD;
&#xD;
          -  Male or female.&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) must agree to use contraception for the&#xD;
             duration of the study. This applies for the time period between signing of the&#xD;
             Informed Consent Form until at least 30 days after the last dose of the study drug.&#xD;
&#xD;
          -  Capable of giving signed informed consent as described in study protocol which&#xD;
             includes compliance with the requirements and restrictions listed in the informed&#xD;
             consent form (ICF) and in this protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any relevant disease (other than those related to hepatic impairment for the hepatic&#xD;
             impaired participants) within 4 weeks prior to study drug administration including&#xD;
             infections and acute gastro-intestinal diseases (vomiting, diarrhea, constipation)&#xD;
             requiring medical treatment.&#xD;
&#xD;
          -  Renal failure with an estimated glomerular filtration rate (eGFR) ≤ 35 mL/min,&#xD;
             according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.&#xD;
&#xD;
          -  Use of strong CYP3A4 and P-glycoprotein inhibitors from 2 weeks before study treatment&#xD;
             until last day of blood sampling for pharmacokinetics after study drug administration.&#xD;
&#xD;
          -  Use of CYP3A4 and P-glycoprotein inducers from 2 weeks before study treatment until&#xD;
             last day of blood sampling for pharmacokinetics after study drug administration.&#xD;
&#xD;
          -  Use of drugs which may affect absorption (e.g. loperamide, metoclopramide), and&#xD;
             systemic administration of any broad-spectrum antibiotic within 1 week before first&#xD;
             study drug administration, unless the drug is part of the mandatory dosing regimen for&#xD;
             treatment of hepatic impairment or related conditions.&#xD;
&#xD;
          -  Indication or evidence for long QT syndrome; Participants in control arm only: QT&#xD;
             interval corrected using Fridericia's method (QTcF) &gt; 450 msec.&#xD;
&#xD;
          -  Ascites qualitatively estimated as severe ascites by physical examination, with need&#xD;
             of paracentesis; or a recent history of paracentesis.&#xD;
&#xD;
          -  Alkaline phosphatase (AP) ≥4 times the upper limit of normal (ULN).&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in conjunction with&#xD;
             gamma-glutamyl transpeptidase (GGT) ≥4 times the ULN (an isolated elevation of GGT&#xD;
             above 4 times ULN will not exclude the participant).&#xD;
&#xD;
          -  International Normalized Ratio (INR) &gt; 2.7.&#xD;
&#xD;
          -  Inability to provide informed consent: Participants with psychiatric disorders,&#xD;
             including hepatic encephalopathy &gt;grade 2, e.g. number connection test &gt;80 seconds.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Clinical Pharmacology of Miami, LLC</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orlando Clinical Research Center</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://clinicaltrials.bayer.com/</url>
    <description>Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.</description>
  </link>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>January 19, 2023</last_update_submitted>
  <last_update_submitted_qc>January 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Safety</keyword>
  <keyword>Tolerability</keyword>
  <keyword>Specific population</keyword>
  <keyword>Subjects with hepatic impairment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</mesh_term>
    <mesh_term>Endometriosis</mesh_term>
    <mesh_term>Urinary Bladder, Overactive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
  </intervention_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/NCT04454424
org study id: 20331
nct id: NCT04454424
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
BAY1817080 is currently under clinical development to treat pain related to unexplained
      chronic cough or chronic cough not affected by a treatment (refractory and/or unexplained
      chronic cough, RUCC), or a condition where the bladder is unable to hold urine normally
      (overactive bladder, OAB) or a condition in which tissue similar to the tissue that normally
      lines the inside of the womb grows outside the womb (endometriosis).

      In this study researchers want to learn more about the safety of BAY1817080, how it is
      tolerated and the way the body absorbs, distributes and gets rid of the study dug given as
      tablet in participants with mild, moderate or severe hepatic impairment and participants with
      normal liver function matched for age-, gender-, weight and race.

      The study will enroll 36 male and female participants in the age between 18 and 79 years.
      Participants with mild or moderate hepatic impairment and the matching participants will take
      multiple oral doses of study drug depending on the study plan. Participants with severe
      hepatic impairment and the matching participants will take a single oral dose of study drug
      during the study. Data from this study will provide researcher important information for
      further development of the study drug in particular on dose recommendation for patients with
      hepatic impairment.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: AUCu after single dose of BAY1817080
time frame: On day 1
description: AUCu: Area under the Curve unbound
measure: Cmax,u after single dose of BAY1817080
time frame: On day 1
description: Cmax,u: maximum observed drug concentration in measured matrix after single dose administration (unbound)
measure: Number of subjects with treatment-emergent adverse events
time frame: from dosing up to 14 days after end of treatment with study medication
measure: AUC (0-12)md,u after multiple dose of BAY1817080
time frame: From day 6 to day 13
description: AUC (0-12)md,u: Area Under the Curve from 0-12 hours at steady state for the multiple dose (unbound)
measure: Cmax,md,u after multiple dose of BAY1817080
time frame: From day 6 to day 13
description: Cmax,md,u: Maximum observed drug concentration at steady state for multiple dose (unbound)
arm group label: Arm A: Child-Pugh A
arm group type: Experimental
description: Participants with mildly impaired hepatic function (Child-Pugh A)
arm group label: Arm B: Child-Pugh B
arm group type: Experimental
description: Participants with moderately impaired hepatic function (Child-Pugh B)
arm group label: Arm C: Child-Pugh C
arm group type: Experimental
description: Participants with severely impaired hepatic function (Child-Pugh C)
arm group label: Arm D: Normal hepatic (Matched A and B)
arm group type: Experimental
description: Participants with normal hepatic function matched to Arm A and B
arm group label: Arm E: Normal hepatic (Matched to C)
arm group type: Experimental
description: Participants with normal hepatic function matched to Arm C
intervention type: Drug
intervention name: BAY1817080
description: Study intervention BAY1817080 will be administered orally with tablet(s).
arm group label: Arm A: Child-Pugh A
arm group label: Arm B: Child-Pugh B
arm group label: Arm C: Child-Pugh C
arm group label: Arm D: Normal hepatic (Matched A and B)
arm group label: Arm E: Normal hepatic (Matched to C)
intervention type: Drug
intervention name: Midazolam
description: Midazolam will be administered intravenously with dose of 0.1 mg on Day 1.
arm group label: Arm A: Child-Pugh A
arm group label: Arm B: Child-Pugh B
arm group label: Arm C: Child-Pugh C
arm group label: Arm D: Normal hepatic (Matched A and B)
arm group label: Arm E: Normal hepatic (Matched to C)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
facility: 
facility: 
country: United States
url: http://clinicaltrials.bayer.com/
description: Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.
responsible party type: Sponsor
mesh term: Neuralgia
mesh term: Endometriosis
mesh term: Urinary Bladder, Overactive
mesh term: Midazolam
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.