<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/NCT02211170</url>
  </required_header>
  <id_info>
    <org_study_id>1175.4</org_study_id>
    <nct_id>NCT02211170</nct_id>
  </id_info>
  <brief_title>Effect of Single Oral Dose BIRB 796 BS on Endotoxin-induced Inflammatory Responses in Healthy Human Subjects</brief_title>
  <official_title>The Effect of Single Oral Dose BIRB 796 BS (50 and 600 mg) on Endotoxin-induced Inflammatory Responses in Healthy Human Subjects. A Placebo-controlled, Randomised, Parallel, Double-blinded Study.</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 determine the effect of a single dose BIRB 796 BS on systemic inflammatory responses&#xD;
      induced by endotoxin in healthy humans&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2000</start_date>
  <primary_completion_date type="Actual">April 2000</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>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction of tumour necrosis factor alpha (TNFα) concentration</measure>
    <time_frame>up to 2 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reduction of pro-inflammatory cytokines (IL-6, IL-8, G-CSF)</measure>
    <time_frame>up to 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of anti-inflammatory cytokine and cytokine inhibitors (IL-10, IL-12p40, soluble TNF receptor (sTNFr) type 1, IL-1ra)</measure>
    <time_frame>up to 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of Acute Phase Proteins (C-reactive protein, Haptoglobin)</measure>
    <time_frame>up to 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of Endothelial Activation Markers (von Willebrand Factor, soluble E-selectin)</measure>
    <time_frame>up to 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of Granulocyte Responses (white blood cell (WBC) count with differential, elastase, elastase-á1-antitrypsin complexes)</measure>
    <time_frame>up to 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of flow Cytometry Cell Surface Markers (Mac-1 (macrophage-1 antigen), L-Selectin)</measure>
    <time_frame>up to 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of ex vivo p38 mitogen-activated protein kinase (MAPK) phosphorylation activity</measure>
    <time_frame>up to 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurence and severity of with chills, nausea, vomiting, abdominal pain, backache, headache, myalgia, fever</measure>
    <time_frame>up to 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant changes in vital signs (pulse rate, systolic and diastolic blood pressure, temperature)</measure>
    <time_frame>up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Global Clinical Tolerability on a 4-point scale</measure>
    <time_frame>after 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>up to 27 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time at which Cmax occurred (tmax)</measure>
    <time_frame>up to 27 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half life (t1/2),</measure>
    <time_frame>up to 27 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve for different time points(AUC)</measure>
    <time_frame>up to 27 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance (CL/F)</measure>
    <time_frame>up to 27 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination rate constant (λz)</measure>
    <time_frame>up to 27 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time (MRT)</measure>
    <time_frame>up to 27 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution (Vz/F)</measure>
    <time_frame>up to 27 hours after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BIBR 796 BS, low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BIBR 796 BS, high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIBR 796 BS, low dose</intervention_name>
    <arm_group_label>BIBR 796 BS, low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIBR 796 BS, high dose</intervention_name>
    <arm_group_label>BIBR 796 BS, high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lipopolysaccharide</intervention_name>
    <description>Lipopolysaccharide (LPS) for endotoxin challenge</description>
    <arm_group_label>BIBR 796 BS, high dose</arm_group_label>
    <arm_group_label>BIBR 796 BS, low dose</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects as determined by results of screening&#xD;
&#xD;
          -  Signed written informed consent in accordance with Good Clinical Practice and local&#xD;
             legislation&#xD;
&#xD;
          -  Age ≥18 and ≤ 35 years&#xD;
&#xD;
          -  Broca ≥- 20 % and ≤ + 20%&#xD;
&#xD;
          -  Able to communicate well with the investigator and to comply with study requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including blood pressure, pulse rate and EKG)&#xD;
             deviating from normal and of clinical relevance&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Surgery of gastrointestinal tract (except appendectomy)&#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 relevant acute infections within 14 days of enrolment&#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 hours) (&lt; 1 month prior to administration&#xD;
             or during the trial)&#xD;
&#xD;
          -  Use of any drugs, which might influence the results of the trial (&lt; 10 days prior to&#xD;
             administration or during the trial)&#xD;
&#xD;
          -  Participation in another trial with an investigational drug (&lt; 3 months prior to&#xD;
             administration or during trial)&#xD;
&#xD;
          -  Smoker (&gt; 10 cigarettes or &gt;3 cigars or &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 or loss &gt; 400 ml (&lt; 2 month prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Excessive physical activities (&lt; 24 hours prior to administration or during the trial)&#xD;
&#xD;
          -  Any laboratory value outside the reference range of clinical relevance&#xD;
&#xD;
          -  History of any familial bleeding disorder&#xD;
&#xD;
          -  Weight &gt; 150 kg&#xD;
&#xD;
          -  Prior confirmed or suspected receipt of a monoclonal antibody&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 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>August 2014</verification_date>
  <study_first_submitted>August 5, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <last_update_submitted>August 5, 2014</last_update_submitted>
  <last_update_submitted_qc>August 5, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 7, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT02211170
org study id: 1175.4
nct id: NCT02211170
lead sponsor: 
Study to determine the effect of a single dose BIRB 796 BS on systemic inflammatory responses
      induced by endotoxin in healthy humans
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Reduction of tumour necrosis factor alpha (TNFα) concentration
time frame: up to 2 days
measure: Reduction of pro-inflammatory cytokines (IL-6, IL-8, G-CSF)
time frame: up to 2 days
measure: Reduction of anti-inflammatory cytokine and cytokine inhibitors (IL-10, IL-12p40, soluble TNF receptor (sTNFr) type 1, IL-1ra)
time frame: up to 2 days
measure: Reduction of Acute Phase Proteins (C-reactive protein, Haptoglobin)
time frame: up to 2 days
measure: Reduction of Endothelial Activation Markers (von Willebrand Factor, soluble E-selectin)
time frame: up to 2 days
measure: Reduction of Granulocyte Responses (white blood cell (WBC) count with differential, elastase, elastase-á1-antitrypsin complexes)
time frame: up to 2 days
measure: Reduction of flow Cytometry Cell Surface Markers (Mac-1 (macrophage-1 antigen), L-Selectin)
time frame: up to 2 days
measure: Reduction of ex vivo p38 mitogen-activated protein kinase (MAPK) phosphorylation activity
time frame: up to 2 days
measure: Occurence and severity of with chills, nausea, vomiting, abdominal pain, backache, headache, myalgia, fever
time frame: up to 2 days
measure: Number of patients with clinically significant changes in vital signs (pulse rate, systolic and diastolic blood pressure, temperature)
time frame: up to 14 days
measure: Number of patients with abnormal changes in laboratory parameters
time frame: up to 14 days
measure: Number of patients with adverse events
time frame: up to 14 days
measure: Assessment of Global Clinical Tolerability on a 4-point scale
time frame: after 14 days
measure: Maximum plasma concentration (Cmax)
time frame: up to 27 hours after drug administration
measure: Time at which Cmax occurred (tmax)
time frame: up to 27 hours after drug administration
measure: Elimination half life (t1/2),
time frame: up to 27 hours after drug administration
measure: Area under the plasma concentration-time curve for different time points(AUC)
time frame: up to 27 hours after drug administration
measure: Apparent clearance (CL/F)
time frame: up to 27 hours after drug administration
measure: Elimination rate constant (λz)
time frame: up to 27 hours after drug administration
measure: Mean residence time (MRT)
time frame: up to 27 hours after drug administration
measure: Apparent volume of distribution (Vz/F)
time frame: up to 27 hours after drug administration
arm group label: BIBR 796 BS, low dose
arm group type: Experimental
arm group label: BIBR 796 BS, high dose
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BIBR 796 BS, low dose
arm group label: BIBR 796 BS, low dose
intervention type: Drug
intervention name: BIBR 796 BS, high dose
arm group label: BIBR 796 BS, high dose
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Drug
intervention name: Lipopolysaccharide
description: Lipopolysaccharide (LPS) for endotoxin challenge
arm group label: BIBR 796 BS, high dose
arm group label: BIBR 796 BS, low dose
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor