<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/NCT02191176</url>
  </required_header>
  <id_info>
    <org_study_id>1134.3</org_study_id>
    <nct_id>NCT02191176</nct_id>
  </id_info>
  <brief_title>Study to Investigate Safety With Special Emphasis on ECG Effects and Tolerability After Oral Doses of Dextromethorphan Hydrobromide Monohydrate in Healthy Male and Female Subjects</brief_title>
  <official_title>A Phase I Multiple Dose Trial to Investigate Safety With Special Emphasis on ECG Effects and Tolerability After Oral Doses of 30 mg q.i.d. and 90 mg q.i.d. Dextromethorphan Hydrobromide Monohydrate (2 mg/mL Syrup) in Healthy Male and Female Subjects for 2 Days Followed by a Morning Dose (Extensive Metabolisers of CYP 2D6) and for 10 Days Followed by a Morning Dose (Poor Metabolisers of CYP 2D6) (Randomised, Double-blind, Placebo-controlled 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>
      The primary objective of the current study is to investigate the safety with special emphasis&#xD;
      on ECG effects, and tolerability of dextromethorphan hydrobromide monohydrate (2mg/mL syrup)&#xD;
      in healthy male and female subjects following oral administration of 30 mg q.i.d. and 90 mg&#xD;
      q.i.d. for 2 days followed by a single morning dose (extensive metabolisers of CYP 2D6) and&#xD;
      for 10 days followed by a single morning dose (poor metabolisers of CYP 2D6).&#xD;
&#xD;
      Additionally pharmacokinetic properties of dextromethorphan and its main metabolites&#xD;
      dextrorphan, 3-hydroxymorphinan, and 3-methoxymorphinan will be investigated&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2009</start_date>
  <primary_completion_date type="Actual">July 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with abnormal findings in physical examination</measure>
    <time_frame>up to day 20</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant changes in vital signs (blood pressure and pulse rate)</measure>
    <time_frame>up to day 20</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically significant changes in 12-lead ECG (electrocardiogram) including QT interval and heart rate corrected QTcN, QTcF (Fridericia) and QTcB (Bazett)</measure>
    <time_frame>up to day 20</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with abnormal changes in laboratory parameters</measure>
    <time_frame>up to day 20</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>day 20 (end of trial examination)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 48 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum measured concentration of the analyte in plasma) after the first dose</measure>
    <time_frame>within 5 hours after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to the maximum concentration of the analyte in plasma) after the first dose</measure>
    <time_frame>within 5 hours after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCt1-t2 (area under the concentration-time curve of the analyte in plasma from the time interval t1 to t2) after the first dose</measure>
    <time_frame>within 5 hours after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-5 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 5 hours after administration) after the first dose</measure>
    <time_frame>within 5 hours after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax,N (maximum measured concentration of the analyte in plasma following the Nth dose) after the last dose</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax,N (time from last dosing to the maximum concentration of the analyte in plasma following the Nth dose) after the last dose</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCt1-t2,N (area under the concentration-time curve of the analyte in plasma from the time interval t1 to t2 following the Nth dose) after the last dose</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-5,N (area under the concentration-time curve of the analyte in plasma over the time interval 0 to 5 hours following the Nth dose) after last dose</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz,N (terminal rate constant in plasma following the Nth dose) after the last dose</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2,N (terminal half-life of the analyte in plasma following the Nth dose) after the last dose</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo,N (mean residence time of the analyte in the body after oral administration of the Nth dose) after the last dose</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum observed concentration of the analyte in plasma) after the second dose</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (Time to Cmax of the analyte in plasma) after the second dose</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Dextromethorphan syrup - low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Dextromethorphan syrup - high dose</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>Dextromethorphan syrup - low dose</intervention_name>
    <arm_group_label>Dextromethorphan syrup - low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dextromethorphan syrup - high dose</intervention_name>
    <arm_group_label>Dextromethorphan syrup - high dose</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 and females according to the following criteria: Based upon a complete&#xD;
             medical history, including the physical examination, oral body temperature, vital&#xD;
             signs (blood pressure, pulse rate), 12-lead Electrocardiogram (ECG), clinical&#xD;
             laboratory tests&#xD;
&#xD;
          -  Age ≥18 and Age ≤55 years&#xD;
&#xD;
          -  BMI ≥18.5 and BMI ≤30 kg/m2 (Body Mass Index)&#xD;
&#xD;
          -  Extensive or poor metabolisers for CYP 2D6 based on the results of a genotyping test&#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 blood pressure, pulse rate and ECG)&#xD;
             deviating from 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 one month prior to&#xD;
             first 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 first administration or&#xD;
             during the trial)&#xD;
&#xD;
          -  Excessive physical activities (within one week prior to first administration or during&#xD;
             the 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 QTc interval of &gt;450 ms;&#xD;
&#xD;
          -  A history of additional risk factors for Torsades de points (e.g., heart failure,&#xD;
             hypokalemia, family history of Long QT Syndrome)&#xD;
&#xD;
        Exclusion criteria specific for this study:&#xD;
&#xD;
          -  Use of drugs that inhibit or induce cytochrome P 450 enzymes, especially CYP2D6,&#xD;
             within 30 days prior to first administration of the study medication or during the&#xD;
             trial&#xD;
&#xD;
        For female subjects:&#xD;
&#xD;
          -  Pregnancy or planning to become pregnant within 2 months of study completion&#xD;
&#xD;
          -  Positive pregnancy test&#xD;
&#xD;
          -  No adequate contraception in woman of child bearing potential during the study, i.e.,&#xD;
             sterilisation, intrauterine device, injectables, oral contraceptive combined with a&#xD;
             barrier method of contraception&#xD;
&#xD;
          -  Lactation period&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 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/1134/1134.3_U10-2388-01.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 16, 2014</study_first_posted>
  <last_update_submitted>July 15, 2014</last_update_submitted>
  <last_update_submitted_qc>July 15, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 16, 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>Dextromethorphan</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/NCT02191176
org study id: 1134.3
nct id: NCT02191176
lead sponsor: 
The primary objective of the current study is to investigate the safety with special emphasis
      on ECG effects, and tolerability of dextromethorphan hydrobromide monohydrate (2mg/mL syrup)
      in healthy male and female subjects following oral administration of 30 mg q.i.d. and 90 mg
      q.i.d. for 2 days followed by a single morning dose (extensive metabolisers of CYP 2D6) and
      for 10 days followed by a single morning dose (poor metabolisers of CYP 2D6).

      Additionally pharmacokinetic properties of dextromethorphan and its main metabolites
      dextrorphan, 3-hydroxymorphinan, and 3-methoxymorphinan will be investigated
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of patients with abnormal findings in physical examination
time frame: up to day 20
measure: Number of patients with clinically significant changes in vital signs (blood pressure and pulse rate)
time frame: up to day 20
measure: Number of patients with clinically significant changes in 12-lead ECG (electrocardiogram) including QT interval and heart rate corrected QTcN, QTcF (Fridericia) and QTcB (Bazett)
time frame: up to day 20
measure: Number of patients with abnormal changes in laboratory parameters
time frame: up to day 20
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: day 20 (end of trial examination)
measure: Number of patients with adverse events
time frame: up to 48 days
measure: Cmax (maximum measured concentration of the analyte in plasma) after the first dose
time frame: within 5 hours after first drug administration
measure: tmax (time from dosing to the maximum concentration of the analyte in plasma) after the first dose
time frame: within 5 hours after first drug administration
measure: AUCt1-t2 (area under the concentration-time curve of the analyte in plasma from the time interval t1 to t2) after the first dose
time frame: within 5 hours after first drug administration
measure: AUC0-5 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 5 hours after administration) after the first dose
time frame: within 5 hours after first drug administration
measure: Cmax,N (maximum measured concentration of the analyte in plasma following the Nth dose) after the last dose
time frame: up to day 13
measure: tmax,N (time from last dosing to the maximum concentration of the analyte in plasma following the Nth dose) after the last dose
time frame: up to day 13
measure: AUCt1-t2,N (area under the concentration-time curve of the analyte in plasma from the time interval t1 to t2 following the Nth dose) after the last dose
time frame: up to day 13
measure: AUC0-5,N (area under the concentration-time curve of the analyte in plasma over the time interval 0 to 5 hours following the Nth dose) after last dose
time frame: up to day 13
measure: λz,N (terminal rate constant in plasma following the Nth dose) after the last dose
time frame: up to day 13
measure: t1/2,N (terminal half-life of the analyte in plasma following the Nth dose) after the last dose
time frame: up to day 13
measure: MRTpo,N (mean residence time of the analyte in the body after oral administration of the Nth dose) after the last dose
time frame: up to day 13
measure: Cmax (maximum observed concentration of the analyte in plasma) after the second dose
time frame: Day 1
measure: tmax (Time to Cmax of the analyte in plasma) after the second dose
time frame: Day 1
arm group label: Dextromethorphan syrup - low dose
arm group type: Experimental
arm group label: Dextromethorphan syrup - high dose
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Dextromethorphan syrup - low dose
arm group label: Dextromethorphan syrup - low dose
intervention type: Drug
intervention name: Dextromethorphan syrup - high dose
arm group label: Dextromethorphan syrup - high dose
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1134/1134.3_U10-2388-01.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Dextromethorphan