<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/NCT02221375</url>
  </required_header>
  <id_info>
    <org_study_id>1256.1</org_study_id>
    <nct_id>NCT02221375</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and Pharmacokinetics of Multiple Rising Doses of Butylated Hydroxytoluene and BI 54903 XX Via Respimat® Soft MistTM Inhaler B in Healthy Male Volunteers</brief_title>
  <official_title>Safety, Tolerability and Pharmacokinetics of Multiple Rising Inhalative Doses of Butylated Hydroxytoluene Via Respimat Soft MistTM Inhaler B (Sub-study 1) and Safety, Tolerability and Pharmacokinetics of Multiple Rising Inhalative Doses of BI 54903 XX Via Respimat Soft MistTM Inhaler B as Randomised, Double-blind, Placebo-controlled Phase I Trial in Healthy Male Volunteers (Main Study) and Comparison of Systemic Exposure Following a Single Dose of BI 54903 XX Via Respimat Soft MistTM Inhaler B and of a Single Dose of Ciclesonide Via MDI (Randomised, Open-label, Two-way Crossover Sub-study 2)</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 objective of the study was to investigate safety, tolerability and pharmacokinetics of&#xD;
      butylated hydroxytoluene (BHT) (sub-study 1) administered via Respimat® Soft MistTM Inhaler B&#xD;
      (SMI B); to assess safety, tolerability and pharmacokinetics of multiple rising doses of BI&#xD;
      54903 XX administered via Respimat® SMI B (main study), and to compare systemic exposure of&#xD;
      single dose BI 54903 XX administered via Respimat® SMI B (sub-study 2) with single dose&#xD;
      Alvesco® (ciclesonide) administered via HFA-134a propellant metered dose inhaler (MDI).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2008</start_date>
  <primary_completion_date type="Actual">September 2008</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 adverse events</measure>
    <time_frame>up to 21 days after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant findings in vitals signs</measure>
    <time_frame>up to 21 days after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant findings in ECG</measure>
    <time_frame>up to 21 days after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant findings in laboratory tests</measure>
    <time_frame>up to 21 days after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Investigator assessed tolerability on a 4-point scale</measure>
    <time_frame>up to 21 days after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in airway resistance (Raw)</measure>
    <time_frame>baseline, after 80 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum measured concentration in plasma)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to maximum measured concentration in plasma)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCτ (area under the concentration-time curve in plasma over a uniform dosing interval τ)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-inf (area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCt1-t2 (area under the concentration-time curve in plasma over the time interval from time t1 to time t2)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve in plasma over the time interval from 0 to the last quantifiable concentration at tz)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>%AUCtz-∞ (the percentage of the AUC 0-∞ that is obtained by extrapolation)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant in plasma)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (terminal half-life in plasma)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTih (mean residence time in the body after inhalation administration)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (apparent clearance in plasma following inhalation administration)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F (apparent volume of distribution during the terminal phase λz following inhalation administration)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aet1-t2 (amount that is eliminated in urine from the time point t1 to time point t2)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fet1-t2 (fraction that is eliminated in urine from time point t1 to time point t2)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLR,t1-t2 (renal clearance from the time point t1 until the time point t2)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio based on Cmax (RA,Cmax)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio based on AUC (RA,AUC)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Linearity index (LI)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolite-to-parent ratio for Cmax (RCmax,Met)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolite-to-parent ratio for AUC (AUCt1-t2,Met)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BHT low</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BHT medium</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BHT high</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 54903 XX low</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 54903 XX medium 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 54903 XX medium 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 54903 XX high</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 54903 XX medium single dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Ciclesonide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BHT low</intervention_name>
    <arm_group_label>BHT low</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BHT medium</intervention_name>
    <arm_group_label>BHT medium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BHT high</intervention_name>
    <arm_group_label>BHT high</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 54903 XX low</intervention_name>
    <arm_group_label>BI 54903 XX low</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 54903 XX medium 1</intervention_name>
    <arm_group_label>BI 54903 XX medium 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 54903 XX medium 2</intervention_name>
    <arm_group_label>BI 54903 XX medium 2</arm_group_label>
    <arm_group_label>BI 54903 XX medium single dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 54903 XX high</intervention_name>
    <arm_group_label>BI 54903 XX high</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ciclesonide</intervention_name>
    <arm_group_label>Ciclesonide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males based upon a complete medical history, including the physical&#xD;
             examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead&#xD;
             Electrocardiogram (ECG) and clinical laboratory tests&#xD;
&#xD;
          -  Age &gt;= 21 and &lt;= 50 years&#xD;
&#xD;
          -  BMI &gt;= 18.5 and &lt;= 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;
        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;
          -  Surgery of the 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 relevant orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of relevant allergy/hypersensitivity (including allergy to drug or its&#xD;
             excipients)&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt;24 h) within at least one month or less than&#xD;
             10 half-lives of the respective drug prior to administration or during the trial&#xD;
&#xD;
          -  Use of drugs that could reasonably influence the results of the trial within 10 days&#xD;
             prior to administration or during the trial (based on the knowledge at the time of&#xD;
             protocol preparation)&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within 2 months prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  Smoker (&gt;10 cigarettes or &gt;3 cigars or &gt;3 pipes per day)&#xD;
&#xD;
          -  Inability to refrain from smoking on trial days&#xD;
&#xD;
          -  Alcohol abuse (more than 60 g per day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (&gt;100 mL within 4 weeks prior to administration or during the trial)&#xD;
&#xD;
          -  Excessive physical activities (within 1 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 the trial site&#xD;
&#xD;
          -  Bacterial and viral infections of the lung, including active or latent tuberculosis&#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 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>August 19, 2014</last_update_submitted>
  <last_update_submitted_qc>August 19, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 20, 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>Ciclesonide</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/NCT02221375
org study id: 1256.1
nct id: NCT02221375
lead sponsor: 
The objective of the study was to investigate safety, tolerability and pharmacokinetics of
      butylated hydroxytoluene (BHT) (sub-study 1) administered via Respimat® Soft MistTM Inhaler B
      (SMI B); to assess safety, tolerability and pharmacokinetics of multiple rising doses of BI
      54903 XX administered via Respimat® SMI B (main study), and to compare systemic exposure of
      single dose BI 54903 XX administered via Respimat® SMI B (sub-study 2) with single dose
      Alvesco® (ciclesonide) administered via HFA-134a propellant metered dose inhaler (MDI).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of patients with adverse events
time frame: up to 21 days after last drug administration
measure: Number of patients with clinically significant findings in vitals signs
time frame: up to 21 days after last drug administration
measure: Number of patients with clinically significant findings in ECG
time frame: up to 21 days after last drug administration
measure: Number of patients with clinically significant findings in laboratory tests
time frame: up to 21 days after last drug administration
measure: Investigator assessed tolerability on a 4-point scale
time frame: up to 21 days after last drug administration
measure: Change in airway resistance (Raw)
time frame: baseline, after 80 hours
measure: Cmax (maximum measured concentration in plasma)
time frame: up to 24 hours after last drug administration
measure: tmax (time from dosing to maximum measured concentration in plasma)
time frame: up to 24 hours after last drug administration
measure: AUCτ (area under the concentration-time curve in plasma over a uniform dosing interval τ)
time frame: up to 24 hours after last drug administration
measure: AUC0-inf (area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 24 hours after last drug administration
measure: AUCt1-t2 (area under the concentration-time curve in plasma over the time interval from time t1 to time t2)
time frame: up to 24 hours after last drug administration
measure: AUC0-tz (area under the concentration-time curve in plasma over the time interval from 0 to the last quantifiable concentration at tz)
time frame: up to 24 hours after last drug administration
measure: %AUCtz-∞ (the percentage of the AUC 0-∞ that is obtained by extrapolation)
time frame: up to 24 hours after last drug administration
measure: λz (terminal rate constant in plasma)
time frame: up to 24 hours after last drug administration
measure: t1/2 (terminal half-life in plasma)
time frame: up to 24 hours after last drug administration
measure: MRTih (mean residence time in the body after inhalation administration)
time frame: up to 24 hours after last drug administration
measure: CL/F (apparent clearance in plasma following inhalation administration)
time frame: up to 24 hours after last drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following inhalation administration)
time frame: up to 24 hours after last drug administration
measure: Aet1-t2 (amount that is eliminated in urine from the time point t1 to time point t2)
time frame: up to 24 hours after last drug administration
measure: fet1-t2 (fraction that is eliminated in urine from time point t1 to time point t2)
time frame: up to 24 hours after last drug administration
measure: CLR,t1-t2 (renal clearance from the time point t1 until the time point t2)
time frame: up to 24 hours after last drug administration
measure: Accumulation ratio based on Cmax (RA,Cmax)
time frame: up to 24 hours after last drug administration
measure: Accumulation ratio based on AUC (RA,AUC)
time frame: up to 24 hours after last drug administration
measure: Linearity index (LI)
time frame: up to 24 hours after last drug administration
measure: Metabolite-to-parent ratio for Cmax (RCmax,Met)
time frame: up to 24 hours after last drug administration
measure: Metabolite-to-parent ratio for AUC (AUCt1-t2,Met)
time frame: up to 24 hours after last drug administration
arm group label: BHT low
arm group type: Experimental
arm group label: BHT medium
arm group type: Experimental
arm group label: BHT high
arm group type: Experimental
arm group label: BI 54903 XX low
arm group type: Experimental
arm group label: BI 54903 XX medium 1
arm group type: Experimental
arm group label: BI 54903 XX medium 2
arm group type: Experimental
arm group label: BI 54903 XX high
arm group type: Experimental
arm group label: BI 54903 XX medium single dose
arm group type: Experimental
arm group label: Ciclesonide
arm group type: Active Comparator
intervention type: Drug
intervention name: BHT low
arm group label: BHT low
intervention type: Drug
intervention name: BHT medium
arm group label: BHT medium
intervention type: Drug
intervention name: BHT high
arm group label: BHT high
intervention type: Drug
intervention name: BI 54903 XX low
arm group label: BI 54903 XX low
intervention type: Drug
intervention name: BI 54903 XX medium 1
arm group label: BI 54903 XX medium 1
intervention type: Drug
intervention name: BI 54903 XX medium 2
arm group label: BI 54903 XX medium 2
arm group label: BI 54903 XX medium single dose
intervention type: Drug
intervention name: BI 54903 XX high
arm group label: BI 54903 XX high
intervention type: Drug
intervention name: Ciclesonide
arm group label: Ciclesonide
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
mesh term: Ciclesonide