<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/NCT02216461</url>
  </required_header>
  <id_info>
    <org_study_id>1219.3</org_study_id>
    <nct_id>NCT02216461</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and Pharmacokinetics of BIBW 2948 BS for HandiHaler® in Healthy Male Volunteers</brief_title>
  <official_title>Safety, Tolerability and Pharmacokinetics of Multiple Rising Inhaled Doses (7.5 to 60 mg Daily for 12 Days) of BIBW 2948 BS Inhalation Powder, Hard Capsule for HandiHaler® in Healthy Male Volunteers (Randomised, Double-blind Placebo-controlled Within Dose Groups)</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 investigate safety, tolerability, and pharmacokinetics of BIBW 2948 BS after repeated&#xD;
      dosing&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2006</start_date>
  <primary_completion_date type="Actual">April 2006</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 patients with clinically significant findings in vital signs</measure>
    <time_frame>Up to day 20 after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant findings in 12-lead electrocardiogram (ECG)</measure>
    <time_frame>Up to day 20 after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant findings in clinical laboratory tests</measure>
    <time_frame>Up to day 20 after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to day 41</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>Up to day 20 after start of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration of the analyte BIBW in plasma at different time points (Cmax)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to maximum measured concentration of the analyte in plasma at different time points (tmax)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ (AUCτ,1)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The percentage of the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to infinity (AUC0-∞) that is obtained by extrapolation (%AUCtz-∞)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant of the analyte in plasma at different time points (λz)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life of the analyte in plasma at different time points (t1/2)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time of the analyte in the body after one administration at different time points (MRTih)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance of the analyte in plasma following extravascular administration at different time points (CL/F)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase λz following an extravascular administration at different time points (Vz/F)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of analyte that is eliminated in urine from at different time points (Ae)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of analyte eliminated in urine at different time points (fe)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance of the analyte at different time points (CLR)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio of the analyte in plasma after multiple dose administration over a uniform dosing interval τ based on Cmax (RA,Cmax,10)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio of the analyte in plasma after multiple dose administration over a uniform dosing interval τ based on AUC0-τ (RA,AUC,10)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Linearity index (AUCτ,ss / AUC0-∞)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in induced sputum analysis (amount of cells, mucin)</measure>
    <time_frame>Pre-dose, 268 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</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 the last quantifiable concentration at tz (AUC0-tz)</measure>
    <time_frame>Pre-dose, up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Low dose of BIBW 2948 BS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Medium dose of BIBW 2948 BS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>High dose of BIBW 2948 BS</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 BIBW 2948 BS for oral inhalation</intervention_name>
    <arm_group_label>Low dose of BIBW 2948 BS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Medium dose of BIBW 2948 BS for oral inhalation</intervention_name>
    <arm_group_label>Medium dose of BIBW 2948 BS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose of BIBW 2948 BS for oral inhalation</intervention_name>
    <arm_group_label>High dose of BIBW 2948 BS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males based on a complete medical history, including the physical examination,&#xD;
             vital signs (BP, PR), 12-lead ECG, clinical laboratory tests&#xD;
&#xD;
          -  Age ≥21 and Age ≤ 50 years&#xD;
&#xD;
          -  BMI (Body Mass Index) ≥18.5 and BMI ≤ 29.9 kg/m2&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with good clinical practice (GCP) and the local legislation&#xD;
&#xD;
          -  Subjects must be current smokers (&lt;10 cigarettes or &lt;3 cigars &lt;3 pipes/day) with a&#xD;
             smoking history &gt;1 year&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including BP, PR and ECG) deviating from&#xD;
             normal and of clinical relevance&#xD;
&#xD;
          -  Any evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          -  History of relevant orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of relevant allergy/hypersensitivity (including allergy to the drug or its&#xD;
             excipients)&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt;24 hours) within at least one month or less&#xD;
             than 10 half-lives of the respective drug prior to administration or during the trial&#xD;
&#xD;
          -  Use of drugs which may have reasonably influenced the results of the trial based on&#xD;
             the knowledge at the time of protocol preparation within 10 days prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within two months prior to&#xD;
             administration or during the 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 (more than 60 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (more than 100 mL within four weeks prior to administration or during&#xD;
             the trial)&#xD;
&#xD;
          -  Excessive physical activities (within one week prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Any laboratory value outside the reference range that is of clinical relevance&#xD;
&#xD;
          -  Inability to comply with dietary regimen of study centre&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>50 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 12, 2014</study_first_submitted>
  <study_first_submitted_qc>August 13, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <last_update_submitted>August 13, 2014</last_update_submitted>
  <last_update_submitted_qc>August 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 15, 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/NCT02216461
org study id: 1219.3
nct id: NCT02216461
lead sponsor: 
To investigate safety, tolerability, and pharmacokinetics of BIBW 2948 BS after repeated
      dosing
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of patients with clinically significant findings in vital signs
time frame: Up to day 20 after start of treatment
measure: Number of patients with clinically significant findings in 12-lead electrocardiogram (ECG)
time frame: Up to day 20 after start of treatment
measure: Number of patients with clinically significant findings in clinical laboratory tests
time frame: Up to day 20 after start of treatment
measure: Number of patients with adverse events
time frame: Up to day 41
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: Up to day 20 after start of treatment
measure: Maximum concentration of the analyte BIBW in plasma at different time points (Cmax)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Time from dosing to maximum measured concentration of the analyte in plasma at different time points (tmax)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ (AUCτ,1)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: The percentage of the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to infinity (AUC0-∞) that is obtained by extrapolation (%AUCtz-∞)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Terminal rate constant of the analyte in plasma at different time points (λz)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Terminal half-life of the analyte in plasma at different time points (t1/2)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Mean residence time of the analyte in the body after one administration at different time points (MRTih)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Apparent clearance of the analyte in plasma following extravascular administration at different time points (CL/F)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Apparent volume of distribution during the terminal phase λz following an extravascular administration at different time points (Vz/F)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Amount of analyte that is eliminated in urine from at different time points (Ae)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Fraction of analyte eliminated in urine at different time points (fe)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Renal clearance of the analyte at different time points (CLR)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Accumulation ratio of the analyte in plasma after multiple dose administration over a uniform dosing interval τ based on Cmax (RA,Cmax,10)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Accumulation ratio of the analyte in plasma after multiple dose administration over a uniform dosing interval τ based on AUC0-τ (RA,AUC,10)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Linearity index (AUCτ,ss / AUC0-∞)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: Changes from baseline in induced sputum analysis (amount of cells, mucin)
time frame: Pre-dose, 268 hours after start of treatment
measure: area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
time frame: Pre-dose, up to 336 hours after start of treatment
measure: area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable concentration at tz (AUC0-tz)
time frame: Pre-dose, up to 336 hours after start of treatment
arm group label: Low dose of BIBW 2948 BS
arm group type: Experimental
arm group label: Medium dose of BIBW 2948 BS
arm group type: Experimental
arm group label: High dose of BIBW 2948 BS
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Low dose of BIBW 2948 BS for oral inhalation
arm group label: Low dose of BIBW 2948 BS
intervention type: Drug
intervention name: Medium dose of BIBW 2948 BS for oral inhalation
arm group label: Medium dose of BIBW 2948 BS
intervention type: Drug
intervention name: High dose of BIBW 2948 BS for oral inhalation
arm group label: High dose of BIBW 2948 BS
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor