<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/NCT02254226</url>
  </required_header>
  <id_info>
    <org_study_id>1184.8</org_study_id>
    <nct_id>NCT02254226</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Salmeterol (Serevent®) After Inhalation With Metered Dose Inhaler (MDI) and Diskus® in Healthy Male Volunteers</brief_title>
  <official_title>A Randomised, Open-label Four-way Crossover Study to Evaluate Pharmacokinetics of Salmeterol (Serevent®) After Inhalation of a 25 μg and 50 μg Single Dose (Metered Dose Inhaler) and a 50 μg and 100 μg Single Dose (Diskus®) 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>
      1. To compare the systemic drug exposure of 100 μg Serevent ® Diskus ® with that of 50 μg&#xD;
           Serevent ® MDI with sufficient precision so that in combination with a second trial it&#xD;
           can be demonstrated that the systemic drug exposure of a new formulation of salmeterol&#xD;
           xinafoate is not superior to that of Serevent ® MDI&#xD;
&#xD;
        2. To test a system of ordered null hypotheses regarding the exposure of two dose levels of&#xD;
           Serevent ® Diskus ® and Serevent ® MDI&#xD;
&#xD;
        3. To get data about the systemic drug exposure of 25 μg Serevent ® MDI and of 50 μg&#xD;
           Serevent ® Diskus ®&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2004</start_date>
  <primary_completion_date type="Actual">January 2005</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>Up to 6 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>Up to 6 hours after drug administration</time_frame>
  </primary_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 time of the last quantifiable data point)</measure>
    <time_frame>Up to 6 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCt1-t2 (Area under the concentration time curve of the analyte in plasma over the time interval t1 to t2)</measure>
    <time_frame>Up to 6 hours after inhalation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to the maximum concentration of the analyte in plasma)</measure>
    <time_frame>Up to 6 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant in plasma)</measure>
    <time_frame>Up to 6 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t½ (terminal half-life of the analyte in plasma)</measure>
    <time_frame>Up to 6 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTinh (mean residence time of the analyte in the body after inhalational administration)</measure>
    <time_frame>Up to 6 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (apparent clearance of the analyte in the plasma after extravascular administration)</measure>
    <time_frame>Up to 6 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)</measure>
    <time_frame>Up to 6 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aet1-t2 (amount of analyte that was eliminated in urine from the time interval t1 to t2)</measure>
    <time_frame>Up to 6 hours after inhalation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2)</measure>
    <time_frame>Up to 6 hours after inhalation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLR,t1-t2 (renal clearance of the analyte in plasma from the time point t1 to t2)</measure>
    <time_frame>Up to 6 hours after inhalation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with abnormal findings in physical examination</measure>
    <time_frame>Up to 15 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with clinically significant changes in vital signs</measure>
    <time_frame>Up to 15 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with abnormal findings in ECG</measure>
    <time_frame>Up to 15 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with abnormal changes in clinical laboratory parameters</measure>
    <time_frame>Up to 15 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>Up to 15 days after last drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Salmeterol MDI low</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Salmeterol MDI high</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Salmeterol Diskus low</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Salmeterol Diskus high</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Salmeterol Diskus low</intervention_name>
    <arm_group_label>Salmeterol Diskus low</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Salmeterol Diskus high</intervention_name>
    <arm_group_label>Salmeterol Diskus high</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Salmeterol MDI low</intervention_name>
    <arm_group_label>Salmeterol MDI low</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Salmeterol MDI high</intervention_name>
    <arm_group_label>Salmeterol MDI high</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy males according to the following criteria:&#xD;
&#xD;
             Based upon a complete medical history, including the physical examination, vital signs&#xD;
             (blood pressure (BP), pulse rate (PR)), 12-lead ECG (electrocardiogram) , clinical&#xD;
             laboratory tests 1.1 No finding deviating from normal and of clinical relevance 1.2 No&#xD;
             evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          2. Age ≥21 and ≤50 years&#xD;
&#xD;
          3. BMI ≥18.5 and &lt;30 kg/m2 (Body Mass Index)&#xD;
&#xD;
          4. 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;
          1. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          2. Surgery of gastrointestinal tract (except appendectomy)&#xD;
&#xD;
          3. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          4. History of relevant orthostatic hypotension, fainting spells or blackouts.&#xD;
&#xD;
          5. Chronic or relevant acute infections&#xD;
&#xD;
          6. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant&#xD;
             to the trial as judged by the investigator&#xD;
&#xD;
          7. Intake of drugs with a long half-life (&gt;24 hours) within at least 1 month or less than&#xD;
             10 half-lives of the respective drug prior to administration or during the trial.&#xD;
&#xD;
          8. Use of drugs which might reasonably influence the results of the trial based on the&#xD;
             knowledge at the time of protocol preparation within 10 days prior to administration&#xD;
             or during the trial.&#xD;
&#xD;
          9. Participation in another trial with an investigational drug within 2 months prior to&#xD;
             administration or during the trial.&#xD;
&#xD;
         10. Smoker (more than 10 cigarettes or three cigars or three pipes per day)&#xD;
&#xD;
         11. Inability to refrain from smoking on trial days&#xD;
&#xD;
         12. Alcohol abuse (more than 60 g/day)&#xD;
&#xD;
         13. Drug abuse&#xD;
&#xD;
         14. Blood donation (more than 100 mL within 4 weeks prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
         15. Excessive physical activities (within 1 week prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
         16. Any laboratory value outside the reference range that is of clinical relevance&#xD;
&#xD;
         17. Inability to comply with dietary regimen of study centre&#xD;
&#xD;
             Exclusion criterion specific for this study:&#xD;
&#xD;
         18. Asthma or history of pulmonary hyperreactivity&#xD;
&#xD;
         19. Allergy / hypersensitivity to Lactose monohydrate&#xD;
&#xD;
         20. Hyperthyrosis&#xD;
&#xD;
         21. Allergic rhinitis in need of treatment&#xD;
&#xD;
         22. Cardiac arrhythmia&#xD;
&#xD;
         23. Paroxysmal tachycardia (&gt; 100 beats per minute)&#xD;
&#xD;
         24. Aortic stenosis&#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>September 2014</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>September 29, 2014</last_update_submitted>
  <last_update_submitted_qc>September 29, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 1, 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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Salmeterol Xinafoate</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/NCT02254226
org study id: 1184.8
nct id: NCT02254226
lead sponsor: 
1. To compare the systemic drug exposure of 100 μg Serevent ® Diskus ® with that of 50 μg
           Serevent ® MDI with sufficient precision so that in combination with a second trial it
           can be demonstrated that the systemic drug exposure of a new formulation of salmeterol
           xinafoate is not superior to that of Serevent ® MDI

        2. To test a system of ordered null hypotheses regarding the exposure of two dose levels of
           Serevent ® Diskus ® and Serevent ® MDI

        3. To get data about the systemic drug exposure of 25 μg Serevent ® MDI and of 50 μg
           Serevent ® Diskus ®
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
time frame: Up to 6 hours after drug administration
measure: Cmax (maximum measured concentration of the analyte in plasma)
time frame: Up to 6 hours after drug administration
measure: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: Up to 6 hours after drug administration
measure: AUCt1-t2 (Area under the concentration time curve of the analyte in plasma over the time interval t1 to t2)
time frame: Up to 6 hours after inhalation
measure: tmax (time from dosing to the maximum concentration of the analyte in plasma)
time frame: Up to 6 hours after drug administration
measure: λz (terminal rate constant in plasma)
time frame: Up to 6 hours after drug administration
measure: t½ (terminal half-life of the analyte in plasma)
time frame: Up to 6 hours after drug administration
measure: MRTinh (mean residence time of the analyte in the body after inhalational administration)
time frame: Up to 6 hours after drug administration
measure: CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
time frame: Up to 6 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
time frame: Up to 6 hours after drug administration
measure: Aet1-t2 (amount of analyte that was eliminated in urine from the time interval t1 to t2)
time frame: Up to 6 hours after inhalation
measure: fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2)
time frame: Up to 6 hours after inhalation
measure: CLR,t1-t2 (renal clearance of the analyte in plasma from the time point t1 to t2)
time frame: Up to 6 hours after inhalation
measure: Number of participants with abnormal findings in physical examination
time frame: Up to 15 days after last drug administration
measure: Number of participants with clinically significant changes in vital signs
time frame: Up to 15 days after last drug administration
measure: Number of participants with abnormal findings in ECG
time frame: Up to 15 days after last drug administration
measure: Number of participants with abnormal changes in clinical laboratory parameters
time frame: Up to 15 days after last drug administration
measure: Number of participants with adverse events
time frame: Up to 15 days after last drug administration
arm group label: Salmeterol MDI low
arm group type: Experimental
arm group label: Salmeterol MDI high
arm group type: Active Comparator
arm group label: Salmeterol Diskus low
arm group type: Experimental
arm group label: Salmeterol Diskus high
arm group type: Experimental
intervention type: Drug
intervention name: Salmeterol Diskus low
arm group label: Salmeterol Diskus low
intervention type: Drug
intervention name: Salmeterol Diskus high
arm group label: Salmeterol Diskus high
intervention type: Drug
intervention name: Salmeterol MDI low
arm group label: Salmeterol MDI low
intervention type: Drug
intervention name: Salmeterol MDI high
arm group label: Salmeterol MDI high
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: Respiratory Aspiration
mesh term: Salmeterol Xinafoate