<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/NCT02254096</url>
  </required_header>
  <id_info>
    <org_study_id>1195.1</org_study_id>
    <nct_id>NCT02254096</nct_id>
  </id_info>
  <brief_title>Safety, Pharmacokinetics and Pharmacodynamics of BIRT 1696 BS in Healthy Human Subjects</brief_title>
  <official_title>Safety, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BIRT 1696 BS as a Solution (10, 100, 400, 1000, 2000, 3000 mg) in 15 ml PEG 400 to Healthy Human Subjects. A Three Part Study: Part 1 Placebo-controlled, Randomised, Dose Escalating Double Blinded Within Each Dose Level; Part 2 Open Label Grapefruit Juice Effect in 100 mg Dose Level Group; Part 3 Open Label Food Effect in 400 mg Dose Level Group</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The objectives are:&#xD;
&#xD;
        1. To assess safety, pharmacokinetics, and pharmacodynamics of BIRT 1696 BS in rising&#xD;
           single doses.&#xD;
&#xD;
        2. To assess safety, pharmacokinetics, and pharmacodynamics of single dose of 100 mg BIRT&#xD;
           1696 BS after grapefruit juice.&#xD;
&#xD;
        3. To asses safety and pharmacokinetics of single dose of 400 mg BIRT 1696 BS after a 67 g&#xD;
           fat and high caloric breakfast.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2002</start_date>
  <primary_completion_date type="Actual">July 2002</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>Number of subjects with adverse events</measure>
    <time_frame>up to 44 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with clinically significant changes in vital signs</measure>
    <time_frame>up to 44 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 44 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal findings in electrocardiogram</measure>
    <time_frame>up to 44 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with abnormal findings in physical examination</measure>
    <time_frame>up to 44 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of tolerability on a verbal rating scale</measure>
    <time_frame>up to 44 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration (Cmax)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total area under the plasma drug concentration-time curve from time zero to infinity (AUC0-∞)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to the maximum plasma concentration (tmax)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life (t1/2)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total apparent oral clearance of drug from plasma after oral administration (CL/F)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution based on terminal elimination phase, divided by F (bioavailability factor) (Vz/F)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time (MRT)</measure>
    <time_frame>up to 48 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinary excretion</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Receptor occupancy as determined by binding of anti-lymphocyte function associated antigen-1 antibody fragment (Fab)</measure>
    <time_frame>up to 168 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inhibition of superantigen induced interleukin-2 production ex vivo</measure>
    <time_frame>up to 168 hours after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BIRT 1696 BS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single escalating dose phase</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BIRT 1696 BS + GFJ</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single dose grapefruit effect arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BIRT 1696 BS + HFM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single dose food effect arm</description>
  </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>BIRT 1696 BS</intervention_name>
    <arm_group_label>BIRT 1696 BS</arm_group_label>
    <arm_group_label>BIRT 1696 BS + GFJ</arm_group_label>
    <arm_group_label>BIRT 1696 BS + HFM</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>Other</intervention_type>
    <intervention_name>Grapefruit juice (GFJ)</intervention_name>
    <arm_group_label>BIRT 1696 BS + GFJ</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High fat meal (HFM)</intervention_name>
    <arm_group_label>BIRT 1696 BS + HFM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male or female subjects as determined by results of screening&#xD;
&#xD;
          -  Signed written informed consent in accordance with Good Clinical Practice (GCP) and&#xD;
             local legislation&#xD;
&#xD;
          -  Age ≥18 and ≤60 years&#xD;
&#xD;
          -  Body Mass Index ≥18.5 and ≤29.9 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subjects who are lactating or of child bearing potential as defined by&#xD;
             surgically sterile or post menopausal (no periods for at least 12 months and elevated&#xD;
             follicle stimulating hormone with low estradiol while on no estrogen supplementation&#xD;
             unless surgically sterile). Females should use barrier contraception (e.g. condoms)&#xD;
             prior to administration of study medication, during the study and at least one month&#xD;
             after release from the study. Women must have had negative blood pregnancy tests&#xD;
&#xD;
          -  Any finding of the medical examination (including blood pressure, pulse rate, and&#xD;
             electrocardiogram) deviating from normal and of clinical relevance&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic&#xD;
             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;
          -  Relevant history of orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          -  Chronic or 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 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; 2 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;
          -  Alcohol abuse (&gt; 60 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Use of methylxanthine-containing drinks or foods (coffee, tea, cola, energy drinks,&#xD;
             chocolate, etc.), grapefruit or grapefruit juice, alcohol, green tea, or tobacco &lt; 5&#xD;
             days prior to administration of study drug or during trial&#xD;
&#xD;
          -  Blood donation or loss &gt; 400 mL, &lt; 1 month prior to administration or during the trial&#xD;
&#xD;
          -  Excessive physical activities &lt; 5 days prior to administration of study drug or during&#xD;
             trial&#xD;
&#xD;
          -  Clinically relevant laboratory abnormalities&#xD;
&#xD;
          -  Any ECG value outside of the reference range of clinical relevance including, but not&#xD;
             limited to QRS interval &gt; 110 ms or QTcB &gt; 450 ms (males) or QTcB &gt; 470 ms (females)&#xD;
&#xD;
          -  Inability to comply with dietary regimen of study centre&#xD;
&#xD;
          -  Inability to comply with the investigator's instructions&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 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>September 2014</verification_date>
  <study_first_submitted>September 30, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>September 30, 2014</last_update_submitted>
  <last_update_submitted_qc>September 30, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 1, 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/NCT02254096
org study id: 1195.1
nct id: NCT02254096
lead sponsor: 
The objectives are:

        1. To assess safety, pharmacokinetics, and pharmacodynamics of BIRT 1696 BS in rising
           single doses.

        2. To assess safety, pharmacokinetics, and pharmacodynamics of single dose of 100 mg BIRT
           1696 BS after grapefruit juice.

        3. To asses safety and pharmacokinetics of single dose of 400 mg BIRT 1696 BS after a 67 g
           fat and high caloric breakfast.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of subjects with adverse events
time frame: up to 44 days
measure: Number of subjects with clinically significant changes in vital signs
time frame: up to 44 days
measure: Number of subjects with abnormal changes in laboratory parameters
time frame: up to 44 days
measure: Number of subjects with abnormal findings in electrocardiogram
time frame: up to 44 days
measure: Number of subjects with abnormal findings in physical examination
time frame: up to 44 days
measure: Assessment of tolerability on a verbal rating scale
time frame: up to 44 days
measure: Maximum observed plasma concentration (Cmax)
time frame: up to 48 hours after drug administration
measure: Total area under the plasma drug concentration-time curve from time zero to infinity (AUC0-∞)
time frame: up to 48 hours after drug administration
measure: Time to the maximum plasma concentration (tmax)
time frame: up to 48 hours after drug administration
measure: Elimination half-life (t1/2)
time frame: up to 48 hours after drug administration
measure: Total apparent oral clearance of drug from plasma after oral administration (CL/F)
time frame: up to 48 hours after drug administration
measure: Apparent volume of distribution based on terminal elimination phase, divided by F (bioavailability factor) (Vz/F)
time frame: up to 48 hours after drug administration
measure: Mean residence time (MRT)
time frame: up to 48 hours after drug administration
measure: Urinary excretion
time frame: up to 24 hours after drug administration
measure: Receptor occupancy as determined by binding of anti-lymphocyte function associated antigen-1 antibody fragment (Fab)
time frame: up to 168 hours after drug administration
measure: Inhibition of superantigen induced interleukin-2 production ex vivo
time frame: up to 168 hours after drug administration
arm group label: BIRT 1696 BS
arm group type: Experimental
description: single escalating dose phase
arm group label: BIRT 1696 BS + GFJ
arm group type: Experimental
description: single dose grapefruit effect arm
arm group label: BIRT 1696 BS + HFM
arm group type: Experimental
description: single dose food effect arm
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BIRT 1696 BS
arm group label: BIRT 1696 BS
arm group label: BIRT 1696 BS + GFJ
arm group label: BIRT 1696 BS + HFM
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Other
intervention name: Grapefruit juice (GFJ)
arm group label: BIRT 1696 BS + GFJ
intervention type: Other
intervention name: High fat meal (HFM)
arm group label: BIRT 1696 BS + HFM
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor