<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/NCT02194283</url>
  </required_header>
  <id_info>
    <org_study_id>18.493</org_study_id>
    <nct_id>NCT02194283</nct_id>
  </id_info>
  <brief_title>Study to Evaluate Safety, Tolerability and Pharmacokinetics of Increasing Repeated Oral Doses of Ambroxol Lozenges in Healthy Male Volunteers</brief_title>
  <official_title>A Double-blind (at Each Dose Level), Randomised, Placebo Controlled Phase I Study to Evaluate Safety, Tolerability and Pharmacokinetics of Increasing Repeated Oral Doses of Ambroxol Lozenges (Dosage: 20, 40, 80 mg Three Times Daily) Over 4 Days 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>
      The main objectives of the present study are to determine pharmacokinetics of ambroxol in&#xD;
      healthy male volunteers following repeated administration of lozenges of 20 mg ambroxol for&#xD;
      four days&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2009</start_date>
  <primary_completion_date type="Actual">November 2009</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax (maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>tmax (time from dosing to the maximum concentration of the analyte in plasma)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ae0-24 (amount of the analyte that is eliminated in urine from the time point 0 until time point 24)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>CLR,0-24 (renal clearance of the analyte determined from the time point 0 until time point 24) using AUC0-24 and Ae0-24</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax,ss (maximum concentration of the analyte in plasma at steady state)</measure>
    <time_frame>up to 120 hours after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>tmax,ss (time from last dosing to maximum concentration at steady state)</measure>
    <time_frame>up to 120 hours after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmin,ss (minimum concentration of the analyte in plasma at steady state)</measure>
    <time_frame>up to 120 hours after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC72-96,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform 24 hour interval matching Day 1)</measure>
    <time_frame>up to 96 hours after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ae72-96,ss (amount of analyte that is eliminated in urine at steady state from the time point 72 to time point 96)</measure>
    <time_frame>up to 96 hours after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>CLR,72-96,ss (renal clearance of the analyte in plasma from the time point 72 until the time point 96 at steady state) using AUC72-96 and Ae72-96</measure>
    <time_frame>up to 96 hours after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>λz,ss (terminal rate constant in plasma at steady state)</measure>
    <time_frame>up to 120 hours after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>t1/2,ss (terminal half-life of the analyte in plasma at steady state)</measure>
    <time_frame>up to 120 hours after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>RA (accumulation ratio)</measure>
    <time_frame>up to 96 hours after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>LI (linearity index)</measure>
    <time_frame>up to 96 hours after first drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 36 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 36 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant changes in vital signs (blood pressure [BP], pulse rate [PR])</measure>
    <time_frame>up to 36 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG)</measure>
    <time_frame>up to 36 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability on a 4-point scale</measure>
    <time_frame>10 days after last drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Ambroxol - in single rising doses</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>Ambroxol - in single rising doses</intervention_name>
    <arm_group_label>Ambroxol - in single rising doses</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 according to the following criteria: Based upon a complete medical&#xD;
             history, including the physical examination, vital signs, 12-lead Electrocardiogram&#xD;
             (ECG), clinical laboratory tests&#xD;
&#xD;
          -  Age ≥21 and Age ≤50 year&#xD;
&#xD;
          -  BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)&#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 vital signs 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 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 might reasonably influence the results of the trial or that prolong&#xD;
             the QT/QTc interval based on the knowledge at the time of protocol preparation within&#xD;
             10 days prior to 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;
          -  Actual smoker&#xD;
&#xD;
          -  Alcohol abuse (more than 40 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 trial site&#xD;
&#xD;
          -  A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a&#xD;
             QTc interval &gt;450 ms)&#xD;
&#xD;
          -  A history of additional risk factors for torsade de pointes (e.g., heart failure,&#xD;
             hypokalaemia, family history of Long QT Syndrome)&#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/content/dam/internet/opu/clinicaltrial/com_EN/results/18/18.493_U10-1795-01.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 17, 2014</study_first_submitted>
  <study_first_submitted_qc>July 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 18, 2014</study_first_posted>
  <last_update_submitted>July 22, 2014</last_update_submitted>
  <last_update_submitted_qc>July 22, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 23, 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>Ambroxol</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/NCT02194283
org study id: 18.493
nct id: NCT02194283
lead sponsor: 
The main objectives of the present study are to determine pharmacokinetics of ambroxol in
      healthy male volunteers following repeated administration of lozenges of 20 mg ambroxol for
      four days
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Cmax (maximum measured concentration of the analyte in plasma)
time frame: up to 24 hours after drug administration
measure: tmax (time from dosing to the maximum concentration of the analyte in plasma)
time frame: up to 24 hours after drug administration
measure: AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours)
time frame: up to 24 hours after drug administration
measure: Ae0-24 (amount of the analyte that is eliminated in urine from the time point 0 until time point 24)
time frame: up to 24 hours after drug administration
measure: CLR,0-24 (renal clearance of the analyte determined from the time point 0 until time point 24) using AUC0-24 and Ae0-24
time frame: up to 24 hours after drug administration
measure: Cmax,ss (maximum concentration of the analyte in plasma at steady state)
time frame: up to 120 hours after first drug administration
measure: tmax,ss (time from last dosing to maximum concentration at steady state)
time frame: up to 120 hours after first drug administration
measure: Cmin,ss (minimum concentration of the analyte in plasma at steady state)
time frame: up to 120 hours after first drug administration
measure: AUC72-96,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform 24 hour interval matching Day 1)
time frame: up to 96 hours after first drug administration
measure: Ae72-96,ss (amount of analyte that is eliminated in urine at steady state from the time point 72 to time point 96)
time frame: up to 96 hours after first drug administration
measure: CLR,72-96,ss (renal clearance of the analyte in plasma from the time point 72 until the time point 96 at steady state) using AUC72-96 and Ae72-96
time frame: up to 96 hours after first drug administration
measure: λz,ss (terminal rate constant in plasma at steady state)
time frame: up to 120 hours after first drug administration
measure: t1/2,ss (terminal half-life of the analyte in plasma at steady state)
time frame: up to 120 hours after first drug administration
measure: RA (accumulation ratio)
time frame: up to 96 hours after first drug administration
measure: LI (linearity index)
time frame: up to 96 hours after first drug administration
measure: Number of patients with adverse events
time frame: up to 36 days
measure: Number of patients with abnormal changes in laboratory parameters
time frame: up to 36 days
measure: Number of patients with clinically significant changes in vital signs (blood pressure [BP], pulse rate [PR])
time frame: up to 36 days
measure: Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG)
time frame: up to 36 days
measure: Assessment of tolerability on a 4-point scale
time frame: 10 days after last drug administration
arm group label: Ambroxol - in single rising doses
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Ambroxol - in single rising doses
arm group label: Ambroxol - in single rising doses
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/content/dam/internet/opu/clinicaltrial/com_EN/results/18/18.493_U10-1795-01.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Ambroxol