<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/NCT02256722</url>
  </required_header>
  <id_info>
    <org_study_id>1207.26</org_study_id>
    <nct_id>NCT02256722</nct_id>
  </id_info>
  <brief_title>In Vivo Specificity of KUC 7483 CL Co-administered With Bisoprolol, Propranolol, and Acipimox in Healthy Male Subjects</brief_title>
  <official_title>A Randomised, Open Label, Four-way Crossover Phase I Trial to Investigate the in Vivo Specificity of a Single Oral Dose of 320 mg KUC 7483 CL Co-administered With Bisoprolol (10 mg Daily), Propranolol (160 mg Daily), and Acipimox (500 mg Daily) Over 5 Days and a Single Inhalative Dose of 100 μg Salmeterol in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Study to compare the metabolic and electrolyte effects of a single oral dose of 320 mg&#xD;
      ritobegron administered alone or with a pre- and comedication with bisoprolol, propranolol&#xD;
      and acipimox. In addition, to compare the metabolic and electrolyte effects of a single dose&#xD;
      of 320 mg ritobegron with those of a single inhalatory dose of 100 μg salmeterol&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2005</start_date>
  <primary_completion_date type="Actual">November 2005</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Absolute change from baseline in glucose</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage change from baseline in glucose</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Absolute change from baseline in free fatty acids (FFA)</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage change from baseline in FFA</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Absolute change from baseline in insulin</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage change from baseline in insulin</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Absolute change from baseline in C-Peptide</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage change from baseline in C-Peptide</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Absolute change from baseline in Potassium</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage change from baseline in Potassium</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Absolute change from baseline in Magnesium</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage change from baseline in Magnesium</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Absolute change from baseline in cAMP</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage change from baseline in cAMP</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 80 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically relevant changes in laboratory tests</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically relevant changes in vital signs</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically relevant findings in electrocardiogram</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically relevant changes in physical examination</measure>
    <time_frame>Baseline, within 10 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum measured concentration of the analyte in plasma</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to the maximum concentration of the analyte in plasma</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 4 hours</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment E</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KUC 7483 CL</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bisoprolol</intervention_name>
    <arm_group_label>Treatment B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propranolol</intervention_name>
    <arm_group_label>Treatment C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acipimox</intervention_name>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Salmeterol</intervention_name>
    <arm_group_label>Treatment E</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male&#xD;
&#xD;
          -  Age &gt;= 30 and &lt;= 60 years&#xD;
&#xD;
          -  Body Mass Index (BMI) &gt;= 18.5 and &lt;= 29.9 kg/m2&#xD;
&#xD;
          -  Signed and dated written informed consent in accordance with Good Clinical Practice&#xD;
             and local legislation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including blood pressure, pulse rate and ECG)&#xD;
             deviating from normal and of clinical relevance&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders, clinically relevant electrolyte disturbances&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          -  History of orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          -  Chronic or clinically relevant acute infections&#xD;
&#xD;
          -  History of allergy/hypersensitivity (including drug allergy) which is deemed relevant&#xD;
             to the trial as judged by the investigator&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt; 24:00 hours) within at least one month or&#xD;
             less than ten half-lives of the respective drug before enrolment in the study or&#xD;
             during the study&#xD;
&#xD;
          -  Use of any drugs which might influence the results of the trial up to 7 days prior to&#xD;
             enrolment in the study or during the study&#xD;
&#xD;
          -  Participation in another trial with an investigational drug (within two months prior&#xD;
             to administration or during the trial)&#xD;
&#xD;
          -  Smoker (&gt; 10 cigarettes or &gt; 3 cigars of &gt; 3 pipes/day)&#xD;
&#xD;
          -  Inability to refrain from smoking on trial days&#xD;
&#xD;
          -  Alcohol abuse (&gt; 60 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (&gt; 100 mL within four weeks prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Any laboratory value outside the reference range if indicative of underlying disease&#xD;
             or poor health&#xD;
&#xD;
          -  Excessive physical activities within the last week before the trial or during the&#xD;
             trial&#xD;
&#xD;
          -  Hypersensitivity to treatment medication, salmeterol and/or related drugs of these&#xD;
             classes&#xD;
&#xD;
          -  Congenital or documented acquired QT- prolongation, previous history of symptomatic&#xD;
             arrhythmias&#xD;
&#xD;
          -  Systolic BP &lt; 115 mmHg&#xD;
&#xD;
          -  Heart rate at rest of &gt; 80 bpm or &lt; 55 bpm&#xD;
&#xD;
          -  Any screening ECG value outside of the reference range of clinical relevance&#xD;
             including, but not limited to PR interval &gt; 220 ms, QRS interval &gt; 115 ms, QTcB &gt; 420&#xD;
             ms, or QT (uncorrected) &gt; 450 ms&#xD;
&#xD;
          -  History of asthma or obstructive pulmonary disease.&#xD;
&#xD;
          -  Psoriasis (own medical history or relative)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <last_update_submitted>October 2, 2014</last_update_submitted>
  <last_update_submitted_qc>October 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 6, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Propranolol</mesh_term>
    <mesh_term>Bisoprolol</mesh_term>
    <mesh_term>Acipimox</mesh_term>
    <mesh_term>Salmeterol Xinafoate</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/NCT02256722
org study id: 1207.26
nct id: NCT02256722
lead sponsor: 
Study to compare the metabolic and electrolyte effects of a single oral dose of 320 mg
      ritobegron administered alone or with a pre- and comedication with bisoprolol, propranolol
      and acipimox. In addition, to compare the metabolic and electrolyte effects of a single dose
      of 320 mg ritobegron with those of a single inhalatory dose of 100 μg salmeterol
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Absolute change from baseline in glucose
time frame: up to 24 hours after administration of study drug
measure: Percentage change from baseline in glucose
time frame: up to 24 hours after administration of study drug
measure: Absolute change from baseline in free fatty acids (FFA)
time frame: up to 24 hours after administration of study drug
measure: Percentage change from baseline in FFA
time frame: up to 24 hours after administration of study drug
measure: Absolute change from baseline in insulin
time frame: up to 24 hours after administration of study drug
measure: Percentage change from baseline in insulin
time frame: up to 24 hours after administration of study drug
measure: Absolute change from baseline in C-Peptide
time frame: up to 24 hours after administration of study drug
measure: Percentage change from baseline in C-Peptide
time frame: up to 24 hours after administration of study drug
measure: Absolute change from baseline in Potassium
time frame: up to 24 hours after administration of study drug
measure: Percentage change from baseline in Potassium
time frame: up to 24 hours after administration of study drug
measure: Absolute change from baseline in Magnesium
time frame: up to 24 hours after administration of study drug
measure: Percentage change from baseline in Magnesium
time frame: up to 24 hours after administration of study drug
measure: Absolute change from baseline in cAMP
time frame: up to 24 hours after administration of study drug
measure: Percentage change from baseline in cAMP
time frame: up to 24 hours after administration of study drug
measure: Number of subjects with adverse events
time frame: up to 80 days
measure: Number of subjects with clinically relevant changes in laboratory tests
time frame: up to 24 hours after administration of study drug
measure: Number of subjects with clinically relevant changes in vital signs
time frame: up to 24 hours after administration of study drug
measure: Number of subjects with clinically relevant findings in electrocardiogram
time frame: up to 24 hours after administration of study drug
measure: Number of subjects with clinically relevant changes in physical examination
time frame: Baseline, within 10 days after last drug administration
measure: Maximum measured concentration of the analyte in plasma
time frame: up to 24 hours after administration of study drug
measure: Time from dosing to the maximum concentration of the analyte in plasma
time frame: up to 24 hours after administration of study drug
measure: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 4 hours
time frame: up to 24 hours after administration of study drug
arm group label: Treatment A
arm group type: Experimental
arm group label: Treatment B
arm group type: Experimental
arm group label: Treatment C
arm group type: Experimental
arm group label: Treatment D
arm group type: Experimental
arm group label: Treatment E
arm group type: Active Comparator
intervention type: Drug
intervention name: KUC 7483 CL
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
intervention type: Drug
intervention name: Bisoprolol
arm group label: Treatment B
intervention type: Drug
intervention name: Propranolol
arm group label: Treatment C
intervention type: Drug
intervention name: Acipimox
arm group label: Treatment D
intervention type: Drug
intervention name: Salmeterol
arm group label: Treatment E
criteria: 
gender: Male
minimum age: 30 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Propranolol
mesh term: Bisoprolol
mesh term: Acipimox
mesh term: Salmeterol Xinafoate