<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/NCT02259881</url>
  </required_header>
  <id_info>
    <org_study_id>1192.11</org_study_id>
    <nct_id>NCT02259881</nct_id>
  </id_info>
  <brief_title>Effect of BIBT 986 Followed by BIBT 986 Given as IV Infusion on Tissue Factor Triggered Coagulation in Healthy Male Volunteers</brief_title>
  <official_title>Investigation of the Effect of 0.9, 2.25 or 4.5 mg of BIBT 986 Over 1 Hour, Followed by 0.2, 0.5 or 1.0 mg/Hour of BIBT 986 for 7 Hours Given as IV Infusion on Tissue Factor Triggered Coagulation in a Randomised, Placebo Controlled, Dose Escalation Design in Healthy Male Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      To compare with placebo the anticoagulant activity of three dosages of BIBT 986 on parameters&#xD;
      of coagulation, platelet activation and inflammation in a model of tissue factor triggered&#xD;
      activation of the coagulation system; to examine the safety of BIBT 986 in this setting&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2002</start_date>
  <primary_completion_date type="Actual">May 2003</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>Change in activated partial thromboplastin time (aPTT)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in international normalized ratio (INR)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in thrombin time (TT)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in ecarin clotting time (ECT)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in prothrombin fragment (F1+2)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in D-dimer</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in thrombin anti-thrombin complexes (TAT)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in protein C activity</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in antithrombin</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in thrombomodulin</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in tissue factor messenger RNA (mRNA)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in platelet count</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in plasmin antiplasmin complexes (PAP)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in soluble P-selectin</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in tumor necrosis factor alpha (TNF alpha)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in interleukin-6 (IL-6)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in primary haemostasis measured by closure times</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with clinically relevant changes in vital signs</measure>
    <time_frame>up to 14 days after start of treatment</time_frame>
    <description>blood pressure, pulse rate, body temperature</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with clinically relevant changes in laboratory parameters</measure>
    <time_frame>up to 14 days after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 14 days after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with clinically relevant changes in ECG</measure>
    <time_frame>up to 14 days after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in thrombus precursor protein</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in soluble E-selectin</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve (AUC)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration in plasma at the end of the infusion (Cgh)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half-life of BIBT 986 in plasma (t1/2)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time of BIBT 986 in the body after intravenous bolus administration (MRT)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution of BIBT 986 in plasma at steady state (Vss)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution of BIBT 986 during the terminal phase after intravenous infusion (Vz)</measure>
    <time_frame>up to 48 hours after start of treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Low dose of BIBT 986 CL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Medium dose of BIBT 986 CL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>High dose of BIBT 986 CL</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>Low dose of BIBT 986 CL, per i.v. infusion</intervention_name>
    <arm_group_label>Low dose of BIBT 986 CL</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Medium dose of BIBT 986 CL, per i.v. infusion</intervention_name>
    <arm_group_label>Medium dose of BIBT 986 CL</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose of BIBT 986 CL, per i.v. infusion</intervention_name>
    <arm_group_label>High dose of BIBT 986 CL</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 (LPS), single i.v. bolus</intervention_name>
    <description>Endotoxin derived from E. coli bacteria, used for activation of coagulation</description>
    <arm_group_label>High dose of BIBT 986 CL</arm_group_label>
    <arm_group_label>Low dose of BIBT 986 CL</arm_group_label>
    <arm_group_label>Medium dose of BIBT 986 CL</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects as determined by the screening procedure&#xD;
&#xD;
          -  Signed written informed consent form in accordance with good clinical practice (GCP)&#xD;
             and local legislation was available&#xD;
&#xD;
          -  Age ≥ 18 and ≤ 40 years&#xD;
&#xD;
          -  Body mass index: BMI ≥ 18 and ≤ 29.9 kg/m2&#xD;
&#xD;
          -  Normal findings in medical history and physical examination unless the investigator&#xD;
             considered an abnormality to be clinically irrelevant&#xD;
&#xD;
          -  Normal laboratory parameters unless the investigator considered an abnormality to be&#xD;
             clinically irrelevant&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding in the medical examination (including blood pressure, pulse rate, ECG, and&#xD;
             laboratory parameters) deviating from normal and of clinical relevance&#xD;
&#xD;
          -  History of or current gastrointestinal, hepatic, renal, respiratory, cardiovascular,&#xD;
             metabolic, immunologic, autoimmune, hormonal disorders, diseases of the central&#xD;
             nervous system (such as epilepsy), or psychiatric disorders&#xD;
&#xD;
          -  Symptoms of a clinically relevant illness in the 3 weeks before the first trial day&#xD;
&#xD;
          -  History of orthostatic hypotension, fainting spells, and blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of allergy / hypersensitivity (including drug allergy) which was deemed&#xD;
             relevant to the trial as judged by the investigator&#xD;
&#xD;
          -  History of&#xD;
&#xD;
               -  any bleeding disorder including prolonged or habitual bleeding&#xD;
&#xD;
               -  any familial bleeding disorder&#xD;
&#xD;
               -  other haematological disease&#xD;
&#xD;
               -  cerebral bleeding (e.g. after a car accident)&#xD;
&#xD;
               -  commotio cerebri&#xD;
&#xD;
          -  Hereditary deficiency of protein C or S, or a mutation of factor V (Leiden), or any&#xD;
             other known abnormality affecting coagulation, fibrinolysis, or platelet function&#xD;
&#xD;
          -  Platelet count &lt; 150000/μL&#xD;
&#xD;
          -  Any ECG value outside of the reference range of clinical relevance (QRS interval &gt; 110&#xD;
             ms or QTcB (QT interval Bazett correction) &gt; 450 ms will be an obligatory exclusion&#xD;
             criterion)&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt; 24 hours) within 1 month prior to&#xD;
             administration&#xD;
&#xD;
          -  Use of any drugs that might influence the results of the trial within 10 days prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within 2 months prior to&#xD;
             administration or during trial&#xD;
&#xD;
          -  Participation in an LPS trial within the last six weeks&#xD;
&#xD;
          -  Smoker (&gt; 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from&#xD;
             smoking on study days&#xD;
&#xD;
          -  Concurrent or history of drug, alcohol, tobacco or coffee / tea / cola abuse&#xD;
&#xD;
          -  Blood donation within 1 month prior to administration or during the trial&#xD;
&#xD;
          -  Excessive physical activities within 5 days prior to administration or during the&#xD;
             trial&#xD;
&#xD;
          -  Seropositivity for hepatitis B surface antigen (HBs-Ag), hepatitis C virus (HCV), HIV&#xD;
             1, or HIV 2 antibodies&#xD;
&#xD;
          -  Weight over 95 kg&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 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 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <last_update_submitted>October 7, 2014</last_update_submitted>
  <last_update_submitted_qc>October 7, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 9, 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/NCT02259881
org study id: 1192.11
nct id: NCT02259881
lead sponsor: 
To compare with placebo the anticoagulant activity of three dosages of BIBT 986 on parameters
      of coagulation, platelet activation and inflammation in a model of tissue factor triggered
      activation of the coagulation system; to examine the safety of BIBT 986 in this setting
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Change in activated partial thromboplastin time (aPTT)
time frame: up to 48 hours after start of treatment
measure: Change in international normalized ratio (INR)
time frame: up to 48 hours after start of treatment
measure: Change in thrombin time (TT)
time frame: up to 48 hours after start of treatment
measure: Change in ecarin clotting time (ECT)
time frame: up to 48 hours after start of treatment
measure: Change in prothrombin fragment (F1+2)
time frame: up to 48 hours after start of treatment
measure: Change in D-dimer
time frame: up to 48 hours after start of treatment
measure: Change in thrombin anti-thrombin complexes (TAT)
time frame: up to 48 hours after start of treatment
measure: Change in protein C activity
time frame: up to 48 hours after start of treatment
measure: Change in antithrombin
time frame: up to 48 hours after start of treatment
measure: Change in thrombomodulin
time frame: up to 48 hours after start of treatment
measure: Change in tissue factor messenger RNA (mRNA)
time frame: up to 48 hours after start of treatment
measure: Change in platelet count
time frame: up to 48 hours after start of treatment
measure: Change in plasmin antiplasmin complexes (PAP)
time frame: Pre-dose, up to day 14 after start of treatment
measure: Change in soluble P-selectin
time frame: up to 48 hours after start of treatment
measure: Change in tumor necrosis factor alpha (TNF alpha)
time frame: up to 48 hours after start of treatment
measure: Change in interleukin-6 (IL-6)
time frame: up to 48 hours after start of treatment
measure: Change in primary haemostasis measured by closure times
time frame: up to 48 hours after start of treatment
measure: Number of subjects with clinically relevant changes in vital signs
time frame: up to 14 days after start of treatment
description: blood pressure, pulse rate, body temperature
measure: Number of subjects with clinically relevant changes in laboratory parameters
time frame: up to 14 days after start of treatment
measure: Number of subjects with adverse events
time frame: up to 14 days after start of treatment
measure: Number of subjects with clinically relevant changes in ECG
time frame: up to 14 days after start of treatment
measure: Change in thrombus precursor protein
time frame: up to 48 hours after start of treatment
measure: Change in soluble E-selectin
time frame: up to 48 hours after start of treatment
measure: Area under the plasma concentration-time curve (AUC)
time frame: up to 48 hours after start of treatment
measure: Maximum concentration in plasma at the end of the infusion (Cgh)
time frame: up to 48 hours after start of treatment
measure: Apparent terminal half-life of BIBT 986 in plasma (t1/2)
time frame: up to 48 hours after start of treatment
measure: Mean residence time of BIBT 986 in the body after intravenous bolus administration (MRT)
time frame: up to 48 hours after start of treatment
measure: Volume of distribution of BIBT 986 in plasma at steady state (Vss)
time frame: up to 48 hours after start of treatment
measure: Apparent volume of distribution of BIBT 986 during the terminal phase after intravenous infusion (Vz)
time frame: up to 48 hours after start of treatment
arm group label: Low dose of BIBT 986 CL
arm group type: Experimental
arm group label: Medium dose of BIBT 986 CL
arm group type: Experimental
arm group label: High dose of BIBT 986 CL
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Low dose of BIBT 986 CL, per i.v. infusion
arm group label: Low dose of BIBT 986 CL
intervention type: Drug
intervention name: Medium dose of BIBT 986 CL, per i.v. infusion
arm group label: Medium dose of BIBT 986 CL
intervention type: Drug
intervention name: High dose of BIBT 986 CL, per i.v. infusion
arm group label: High dose of BIBT 986 CL
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Drug
intervention name: Lipopolysaccharide (LPS), single i.v. bolus
description: Endotoxin derived from E. coli bacteria, used for activation of coagulation
arm group label: High dose of BIBT 986 CL
arm group label: Low dose of BIBT 986 CL
arm group label: Medium dose of BIBT 986 CL
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor