<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/NCT03773068</url>
  </required_header>
  <id_info>
    <org_study_id>19519</org_study_id>
    <secondary_id>2018-001814-13</secondary_id>
    <nct_id>NCT03773068</nct_id>
  </id_info>
  <brief_title>A Study in Healthy Volunteers Investigating How Quickly and to What Extent BAY1817080 is Taken up, Distributed, Broken Down and Eliminated From the Body, as Well as the Difference Between 2 Different Types of Tablets of BAY1817080 and the Difference Between Oral Dose and Dose in the Vein</brief_title>
  <official_title>Open Label, Partially Randomized, Cross-over Study to Determine the Absolute Bioavailability and Pharmacokinetics of BAY1817080 Using a Simultaneous Anticipated Therapeutic Oral Dose Along With an i.v. [13C715N]-Labeled Microtracer and to Investigate the Relative Bioavailability of Two Formulations Given Under Different Diets at 2 Dose Levels in Healthy Volunteers</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>
      The main purpose of this study is to investigate how quickly and to what extent BAY1817080 is&#xD;
      absorbed (taken up), distributed, metabolized (broken down) and eliminated from the body&#xD;
      (this is called pharmacokinetics). The pharmacokinetics of BAY1817080 administered as tablets&#xD;
      will be compared to the pharmacokinetics of BAY1817080 administered as intravenous (iv; in&#xD;
      the vein) infusion (this is called absolute bioavailability). Furthermore, 2 different types&#xD;
      of tablets with BAY1817080 (Formulation A and Formulation B) will be compared with regard to&#xD;
      pharmacokinetics (this is called relative bioavailability). The effect of a meal on the&#xD;
      pharmacokinetics of BAY1817080 administered as tablets will be investigated as well. Finally,&#xD;
      it will also be investigated how safe BAY1817080 is and how well BAY1817080 is tolerated.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 13, 2018</start_date>
  <completion_date type="Actual">August 12, 2019</completion_date>
  <primary_completion_date type="Actual">June 21, 2019</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Absolute oral bioavailability (F) of BAY1817080</measure>
    <time_frame>Up to 10 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Relative bioavailability (frel) of Formulation A versus Formulation B given under different diets</measure>
    <time_frame>Up to 10 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of a high-fat, high-calorie meal (HF,HC) on the PK of BAY1817080 after a single oral dose of Formulation B at two doses in comparison to the fasted state evaluated by Cmax</measure>
    <time_frame>Up to 10 days</time_frame>
    <description>Maximum observed drug concentration in plasma after single dose administration (Cmax) of BAY1817080 will be analyzed assuming log-normally distributed data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of a high-fat, high-calorie meal (HF,HC) on the PK of BAY1817080 after a single oral dose of Formulation B at two doses in comparison to the fasted state evaluated by AUC</measure>
    <time_frame>Up to 10 days</time_frame>
    <description>Area under the concentration versus time curve from zero to infinity after single dose administration (AUC) of BAY1817080 will be analyzed assuming log-normally distributed data. AUC from time 0 to the last data point greater than lower limit of quantification (AUC[0-tlast]) will be used if AUC cannot be calculated reliably in all subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose proportionality in BAY1817080 PK after a single oral dose of Formulation B across three doses in fasted state evaluated by Cmax/D</measure>
    <time_frame>Up to 10 days</time_frame>
    <description>To investigate dose-proportionality, Cmax divided by dose (Cmax/D) derived from the 3 oral doses of Formulation B in fasted state will be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose proportionality in BAY1817080 PK after a single oral dose of Formulation B across three doses in fasted state evaluated by AUC/D</measure>
    <time_frame>Up to 10 days</time_frame>
    <description>To investigate dose-proportionality, AUC divided by dose (AUC/D) derived from the 3 oral doses of Formulation B in fasted state will be analyzed. AUC(0-tlast)/D will be used if AUC/D cannot be calculated reliably in all subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency and severity of treatment emergent adverse events (TEAEs)</measure>
    <time_frame>Up to 42 days</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Biological Availability</condition>
  <arm_group>
    <arm_group_label>Group 1 - BAY1817080 Dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive one single oral dose of BAY1817080 - Formulation B at dose 1 under fasted condition</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 - BAY1817080 Dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a) one single oral dose of BAY1817080 - Formulation A at dose 2 with moderate-fat, moderate-calorie meal (MF, MC); b) one single oral dose of BAY1817080 - Formulation B at dose 2 along with one intravenous (i.v.) infusion of 0.1 mg [13C715N]-BAY1817080; and c) one single oral dose of BAY1817080 - Formulation B at dose 2 with high-fat, high-calorie meal (HF, HC). The 3 treatments will be administered with a randomized sequence</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3 - BAY1817080 Dose 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a) one single oral dose of BAY1817080 - Formulation B at dose 3 under fasted condition; followed by one single oral dose of BAY1817080 - Formulation A at dose 3 with MF, MC; and followed by one single oral dose of BAY1817080 - Formulation B at dose 3 with HF, HC. The 3 treatments will be administered with a fixed sequence</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BAY1817080 - Formulation A</intervention_name>
    <description>Formulation A</description>
    <arm_group_label>Group 2 - BAY1817080 Dose 2</arm_group_label>
    <arm_group_label>Group 3 - BAY1817080 Dose 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BAY1817080 - Formulation B</intervention_name>
    <description>Formulation B</description>
    <arm_group_label>Group 1 - BAY1817080 Dose 1</arm_group_label>
    <arm_group_label>Group 2 - BAY1817080 Dose 2</arm_group_label>
    <arm_group_label>Group 3 - BAY1817080 Dose 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[13C715N]-BAY 181708 stable isotope label (SIL)</intervention_name>
    <description>0.1 mg [13C715N]-BAY181708, 15 minutes i.v. infusion at the estimated tmax after administration of Formulation B</description>
    <arm_group_label>Group 2 - BAY1817080 Dose 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Healthy male subject&#xD;
&#xD;
          -  Age: 18 to 55 years (inclusive) at the time of informed consent and first dose of&#xD;
             study medication&#xD;
&#xD;
          -  Body mass index (BMI) above/equal to 18 and below/equal to 30 kg/m^2 at Screening&#xD;
&#xD;
          -  Body weight of at least 45 kg at Screening&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Presence or history of clinically relevant cardiovascular, central nervous system&#xD;
             (CNS), hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine&#xD;
             dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic&#xD;
             skin rash&#xD;
&#xD;
          -  Known hypersensitivity to the study drugs&#xD;
&#xD;
          -  Known severe allergies or significant non-allergic drug reactions&#xD;
&#xD;
          -  Febrile illness within 1 week before study drug administration&#xD;
&#xD;
          -  Current or recent (within 6 months) gastrointestinal disease that would be expected to&#xD;
             influence the absorption of drugs&#xD;
&#xD;
          -  Subject has a history of cancer, except basal cell carcinoma which has been in&#xD;
             remission for at least 5 years prior to Screening&#xD;
&#xD;
          -  Poor peripheral venous access&#xD;
&#xD;
          -  Regular use of medicines within 6 months prior to screening&#xD;
&#xD;
          -  Clinically relevant findings in the electrocardiogram (ECG), physical examination or&#xD;
             laboratory examination&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>PRAHealthSciences</name>
      <address>
        <city>Groningen</city>
        <zip>9728 NZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>August 16, 2019</last_update_submitted>
  <last_update_submitted_qc>August 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Endometriosis</keyword>
  <keyword>Refractory chronic cough</keyword>
  <!-- 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/NCT03773068
org study id: 19519
secondary id: 2018-001814-13
nct id: NCT03773068
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The main purpose of this study is to investigate how quickly and to what extent BAY1817080 is
      absorbed (taken up), distributed, metabolized (broken down) and eliminated from the body
      (this is called pharmacokinetics). The pharmacokinetics of BAY1817080 administered as tablets
      will be compared to the pharmacokinetics of BAY1817080 administered as intravenous (iv; in
      the vein) infusion (this is called absolute bioavailability). Furthermore, 2 different types
      of tablets with BAY1817080 (Formulation A and Formulation B) will be compared with regard to
      pharmacokinetics (this is called relative bioavailability). The effect of a meal on the
      pharmacokinetics of BAY1817080 administered as tablets will be investigated as well. Finally,
      it will also be investigated how safe BAY1817080 is and how well BAY1817080 is tolerated.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Absolute oral bioavailability (F) of BAY1817080
time frame: Up to 10 days
measure: Relative bioavailability (frel) of Formulation A versus Formulation B given under different diets
time frame: Up to 10 days
measure: Effect of a high-fat, high-calorie meal (HF,HC) on the PK of BAY1817080 after a single oral dose of Formulation B at two doses in comparison to the fasted state evaluated by Cmax
time frame: Up to 10 days
description: Maximum observed drug concentration in plasma after single dose administration (Cmax) of BAY1817080 will be analyzed assuming log-normally distributed data.
measure: Effect of a high-fat, high-calorie meal (HF,HC) on the PK of BAY1817080 after a single oral dose of Formulation B at two doses in comparison to the fasted state evaluated by AUC
time frame: Up to 10 days
description: Area under the concentration versus time curve from zero to infinity after single dose administration (AUC) of BAY1817080 will be analyzed assuming log-normally distributed data. AUC from time 0 to the last data point greater than lower limit of quantification (AUC[0-tlast]) will be used if AUC cannot be calculated reliably in all subjects.
measure: Dose proportionality in BAY1817080 PK after a single oral dose of Formulation B across three doses in fasted state evaluated by Cmax/D
time frame: Up to 10 days
description: To investigate dose-proportionality, Cmax divided by dose (Cmax/D) derived from the 3 oral doses of Formulation B in fasted state will be analyzed.
measure: Dose proportionality in BAY1817080 PK after a single oral dose of Formulation B across three doses in fasted state evaluated by AUC/D
time frame: Up to 10 days
description: To investigate dose-proportionality, AUC divided by dose (AUC/D) derived from the 3 oral doses of Formulation B in fasted state will be analyzed. AUC(0-tlast)/D will be used if AUC/D cannot be calculated reliably in all subjects.
measure: Frequency and severity of treatment emergent adverse events (TEAEs)
time frame: Up to 42 days
arm group label: Group 1 - BAY1817080 Dose 1
arm group type: Experimental
description: Participants will receive one single oral dose of BAY1817080 - Formulation B at dose 1 under fasted condition
arm group label: Group 2 - BAY1817080 Dose 2
arm group type: Experimental
description: Participants will receive a) one single oral dose of BAY1817080 - Formulation A at dose 2 with moderate-fat, moderate-calorie meal (MF, MC); b) one single oral dose of BAY1817080 - Formulation B at dose 2 along with one intravenous (i.v.) infusion of 0.1 mg [13C715N]-BAY1817080; and c) one single oral dose of BAY1817080 - Formulation B at dose 2 with high-fat, high-calorie meal (HF, HC). The 3 treatments will be administered with a randomized sequence
arm group label: Group 3 - BAY1817080 Dose 3
arm group type: Experimental
description: Participants will receive a) one single oral dose of BAY1817080 - Formulation B at dose 3 under fasted condition; followed by one single oral dose of BAY1817080 - Formulation A at dose 3 with MF, MC; and followed by one single oral dose of BAY1817080 - Formulation B at dose 3 with HF, HC. The 3 treatments will be administered with a fixed sequence
intervention type: Drug
intervention name: BAY1817080 - Formulation A
description: Formulation A
arm group label: Group 2 - BAY1817080 Dose 2
arm group label: Group 3 - BAY1817080 Dose 3
intervention type: Drug
intervention name: BAY1817080 - Formulation B
description: Formulation B
arm group label: Group 1 - BAY1817080 Dose 1
arm group label: Group 2 - BAY1817080 Dose 2
arm group label: Group 3 - BAY1817080 Dose 3
intervention type: Drug
intervention name: [13C715N]-BAY 181708 stable isotope label (SIL)
description: 0.1 mg [13C715N]-BAY181708, 15 minutes i.v. infusion at the estimated tmax after administration of Formulation B
arm group label: Group 2 - BAY1817080 Dose 2
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Netherlands
responsible party type: Sponsor