<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/NCT02220673</url>
  </required_header>
  <id_info>
    <org_study_id>1256.13</org_study_id>
    <nct_id>NCT02220673</nct_id>
  </id_info>
  <brief_title>Serial Lung Function Measurements in Healthy and Mild Asthmatic Adults After Oral Inhalation of Ethanolic Solutions Containing Two Concentrations of the Excipient Butylated Hydroxytoluene (BHT) Administered With the Respimat® B (RMT-B)</brief_title>
  <official_title>Serial Lung Function Measurements in 12 Healthy and 48 Mild Asthmatic Adults After Oral Inhalation of Ethanolic Solutions Containing Two Concentrations of the Excipient Butylated Hydroxytoluene (BHT, 0.1% and 0.5%) Administered With the Respimat® B (RMT-B) vs. Corresponding RMT-B and HFA MDI Without BHT; Repeated Increasing Doses With 2, 4, and 6 Actuations of Low Concentration Prior to High Concentration on Separate Days, Double Blind for RMT-B Use, Randomised 4-way Cross-over Design</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Primary objective: To investigate the safety and local tolerability of increasing cumulative&#xD;
      doses (2, 4, 6 actuations) of a low (0.1%) and a high (0.5%) concentration of BHT&#xD;
      administered via oral inhalation with the Respimat® inhaler B (RMT-B) vs. 2 inhalation&#xD;
      solutions without BHT (placebo to BHT given by RMT B and placebo given by hydroxylfluoralkane&#xD;
      metered dose inhaler (HFA MDI)). In a first step, the trial was performed in healthy subjects&#xD;
      and - if no safety concerns arose - in a second step in patients with mild asthma who were&#xD;
      sensitive to metacholine in a respective challenge test. Secondary objective: To explore the&#xD;
      pharmacokinetics (PK) of BHT.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2009</start_date>
  <primary_completion_date type="Actual">May 2010</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum decrease of forced expiratory volume in one second (FEV1)</measure>
    <time_frame>baseline, 3 h after administration</time_frame>
    <description>(Minimum FEV1 value over the interval 5 min to 2 h 50 min) minus (baseline value)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum decrease in FEV1 after 2 actuations</measure>
    <time_frame>baseline, up to 50 minutes after drug administration</time_frame>
    <description>(minimum FEV1 value over the interval 5 min to 50 min) - (baseline value)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum decrease in FEV1 after 4 actuations</measure>
    <time_frame>baseline, up to 1:50 hours after drug administration</time_frame>
    <description>(minimum FEV1 value over the interval 1 h 5 min to 1 h 50 min) - (baseline value)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum decrease in FEV1 after 6 actuations</measure>
    <time_frame>baseline, up to 2:50 hours after drug administration</time_frame>
    <description>(minimum FEV1 value over the interval 2 h 5 min to 2 h 50 min) - (baseline value)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with a decrease in FEV1</measure>
    <time_frame>baseline, up to 2:50 hours after drug administration</time_frame>
    <description>stratified into classes of 0-20%, &gt;20-40%, and &gt;40%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with cough episodes</measure>
    <time_frame>up to 9 days</time_frame>
    <description>within 5 min prior to the 1st inhalation and within 5 min after each of the 3 inhalations on each treatment day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients requiring rescue medication</measure>
    <time_frame>up to 60 min after each dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 10 days after the last treatment day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>pre-dose, 2, 10, 25 and 55 min after each dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>pre-dose, 2, 10, 25 and 55 min after each dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable concentration at tz)</measure>
    <time_frame>pre-dose, 2, 10, 25 and 55 min after each dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve (AUC) of FEV1</measure>
    <time_frame>over 3 hours after first dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of FEV1</measure>
    <time_frame>over 1 hours after each dosing</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>BHT 0.1%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BHT 0.5%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for RMT-B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for HFA-MDI</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BHT 0.1%</intervention_name>
    <arm_group_label>BHT 0.1%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BHT 0.5%</intervention_name>
    <arm_group_label>BHT 0.5%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for RMT-B</intervention_name>
    <arm_group_label>Placebo for RMT-B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for HFA-MDI</intervention_name>
    <arm_group_label>Placebo for HFA-MDI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Healthy subjects&#xD;
&#xD;
          -  Male or female adult subjects&#xD;
&#xD;
          -  Age ≥ 18 and ≤ 65 years&#xD;
&#xD;
          -  Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2&#xD;
&#xD;
          -  Non-smokers (within the last 5 years)&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the trial in&#xD;
             accordance with Good Clinical Practice (GCP) and the local legislation&#xD;
&#xD;
          -  Proper use of RMT and MDI&#xD;
&#xD;
          -  Able to perform technically satisfactory pulmonary function test&#xD;
&#xD;
        Patients with mild asthma&#xD;
&#xD;
          -  Male or female adult subjects with intermittent and mild persistent asthma&#xD;
&#xD;
          -  Age ≥ 18 and ≤ 65 years&#xD;
&#xD;
          -  Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2&#xD;
&#xD;
          -  FEV1 ≥ 70% predicted and stable for at least 7 days prior to randomization&#xD;
&#xD;
          -  Short acting beta agonist (SABA) response documented in the last 6 months&#xD;
&#xD;
          -  A history of wheeze, cough, dyspnoea or chest tightness following exposure to at least&#xD;
             one of the following: cold, exercise, dry air, smoke, dust, allergens&#xD;
&#xD;
          -  Positive methacholine challenge test reflecting mild to moderate bronchial&#xD;
             hyperreactivity (PC20: 0.25-4.0 mg/mL) performed within two weeks prior randomization&#xD;
             (at visit 1 or between visit 1 and 2)&#xD;
&#xD;
          -  None or stable dosages of pulmonary medications (SABA only) in the past 6 weeks&#xD;
&#xD;
          -  Non smokers or ex-smokers for the last 5 years&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the trial in&#xD;
             accordance with GCP and the local legislation&#xD;
&#xD;
          -  Proper use of RMT and MDI&#xD;
&#xD;
          -  Able to perform technically satisfactory pulmonary function test&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Healthy subjects&#xD;
&#xD;
          -  Any finding in the medical examination (including blood pressure (BP), pulse rate&#xD;
             (PR)) deviating from normal and of clinical relevance&#xD;
&#xD;
          -  Any laboratory value outside the reference range deemed of clinical relevance&#xD;
&#xD;
          -  Pregnant or breast feeding women or women of childbearing potential without having a&#xD;
             negative Human choriongonadotropin, β-subunit (ß-HCG) pregnancy test and without using&#xD;
             a medically approved highly effective method of contraception for the previous 3&#xD;
             months&#xD;
&#xD;
          -  Abnormal spirometry i.e., FEV1 &lt;80% predicted and/or methacholine challenge at&#xD;
             screening Visit 1 (or between Visits 1 and 2)&#xD;
&#xD;
          -  Acute or chronic bacterial and viral infections of the lung&#xD;
&#xD;
          -  History of relevant allergy/hypersensitivity (including allergy to drug or its&#xD;
             excipients)&#xD;
&#xD;
          -  Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular,&#xD;
             metabolic, immunological or hormonal disorders&#xD;
&#xD;
          -  Clinically relevant diseases of the central nervous system (such as epilepsy) or&#xD;
             psychiatric disorders or neurological disorders&#xD;
&#xD;
          -  Use of drugs which might reasonably influence the results of the trial within 10 days&#xD;
             prior to first administration or during the trial (assessed and judged by the&#xD;
             investigator)&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within 1 month prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  Alcohol abuse (more than 60 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (&gt;120 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 vulnerable subjects&#xD;
&#xD;
          -  Inability to comply with protocol requirements, instructions and study related&#xD;
             restrictions, dietary regimen of trial site, and improbability of completing the study&#xD;
&#xD;
        Patients with mild asthma&#xD;
&#xD;
          -  Any finding of the medical examination (including BP, PR) deviating from normal and of&#xD;
             clinical relevance&#xD;
&#xD;
          -  Any laboratory value that was of clinical relevance&#xD;
&#xD;
          -  Moderate or severe persistent asthma&#xD;
&#xD;
          -  Pregnant or breast feeding women or women of childbearing potential without a negative&#xD;
             ß-HCG pregnancy test and without using a medically approved highly effective method of&#xD;
             contraception for the previous 3 months&#xD;
&#xD;
          -  Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular,&#xD;
             metabolic, immunological or hormonal disorders&#xD;
&#xD;
          -  Clinically relevant diseases of the central nervous system (such as epilepsy) or&#xD;
             psychiatric disorders or neurological disorders&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  Treated or non-treated bacterial and viral infections of the lung, including active or&#xD;
             latent tuberculosis&#xD;
&#xD;
          -  Use of any corticosteroids, long acting muscarinic antagonist (LAMA) or long acting&#xD;
             beta agonists (LABA), all within 1 month prior to screening Visit 1 and prior to&#xD;
             administration of investigational product (i.e., allergic patients could only&#xD;
             participate outside their season)&#xD;
&#xD;
          -  Clinically relevant perennial allergies (i.e., which need actual treatment)&#xD;
&#xD;
          -  Methylxanthines, antihistamines, antileukotrienes, cromolyn/nedocromil sodium all&#xD;
             within 1 month prior to screening Visit 1 and prior to administration of&#xD;
             investigational product&#xD;
&#xD;
          -  SABAs 12 h prior to each visit day&#xD;
&#xD;
          -  Use of other drugs which reasonably influence the results of the trial within 10 days&#xD;
             prior to first administration or during the trial (e.g., beta blockers, all&#xD;
             antimuscarinic agents like phenothiazines and some antidepressants)&#xD;
&#xD;
          -  Participation in another trial with an investigational product within 1 month prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  Alcohol abuse (more than 60 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (&gt;120 mL within 4 weeks prior to administration or during the trial)&#xD;
&#xD;
          -  Excessive physical activities (within 3 days prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Inability to comply with protocol requirements, instructions and trial related&#xD;
             restrictions, dietary regimen of trial site, and improbability of completing the trial&#xD;
&#xD;
          -  Any vulnerable patients&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Aspiration</mesh_term>
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Butylated Hydroxytoluene</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/NCT02220673
org study id: 1256.13
nct id: NCT02220673
lead sponsor: 
Primary objective: To investigate the safety and local tolerability of increasing cumulative
      doses (2, 4, 6 actuations) of a low (0.1%) and a high (0.5%) concentration of BHT
      administered via oral inhalation with the Respimat® inhaler B (RMT-B) vs. 2 inhalation
      solutions without BHT (placebo to BHT given by RMT B and placebo given by hydroxylfluoralkane
      metered dose inhaler (HFA MDI)). In a first step, the trial was performed in healthy subjects
      and - if no safety concerns arose - in a second step in patients with mild asthma who were
      sensitive to metacholine in a respective challenge test. Secondary objective: To explore the
      pharmacokinetics (PK) of BHT.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double
measure: Maximum decrease of forced expiratory volume in one second (FEV1)
time frame: baseline, 3 h after administration
description: (Minimum FEV1 value over the interval 5 min to 2 h 50 min) minus (baseline value)
measure: Maximum decrease in FEV1 after 2 actuations
time frame: baseline, up to 50 minutes after drug administration
description: (minimum FEV1 value over the interval 5 min to 50 min) - (baseline value)
measure: Maximum decrease in FEV1 after 4 actuations
time frame: baseline, up to 1:50 hours after drug administration
description: (minimum FEV1 value over the interval 1 h 5 min to 1 h 50 min) - (baseline value)
measure: Maximum decrease in FEV1 after 6 actuations
time frame: baseline, up to 2:50 hours after drug administration
description: (minimum FEV1 value over the interval 2 h 5 min to 2 h 50 min) - (baseline value)
measure: Number of subjects with a decrease in FEV1
time frame: baseline, up to 2:50 hours after drug administration
description: stratified into classes of 0-20%, >20-40%, and >40%
measure: Number of patients with cough episodes
time frame: up to 9 days
description: within 5 min prior to the 1st inhalation and within 5 min after each of the 3 inhalations on each treatment day
measure: Number of patients requiring rescue medication
time frame: up to 60 min after each dosing
measure: Number of patients with adverse events
time frame: up to 10 days after the last treatment day
measure: Cmax (maximum measured concentration of the analyte in plasma)
time frame: pre-dose, 2, 10, 25 and 55 min after each dosing
measure: tmax (time from dosing to maximum measured concentration of the analyte in plasma)
time frame: pre-dose, 2, 10, 25 and 55 min after each dosing
measure: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable concentration at tz)
time frame: pre-dose, 2, 10, 25 and 55 min after each dosing
measure: Area under the curve (AUC) of FEV1
time frame: over 3 hours after first dosing
measure: AUC of FEV1
time frame: over 1 hours after each dosing
arm group label: BHT 0.1%
arm group type: Experimental
arm group label: BHT 0.5%
arm group type: Experimental
arm group label: Placebo for RMT-B
arm group type: Placebo Comparator
arm group label: Placebo for HFA-MDI
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BHT 0.1%
arm group label: BHT 0.1%
intervention type: Drug
intervention name: BHT 0.5%
arm group label: BHT 0.5%
intervention type: Drug
intervention name: Placebo for RMT-B
arm group label: Placebo for RMT-B
intervention type: Drug
intervention name: Placebo for HFA-MDI
arm group label: Placebo for HFA-MDI
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Respiratory Aspiration
mesh term: Asthma
mesh term: Butylated Hydroxytoluene