<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/NCT02215122</url>
  </required_header>
  <id_info>
    <org_study_id>MGR001-1008</org_study_id>
    <nct_id>NCT02215122</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study to Assess Systemic Exposure of FP and SAL FDC From Different DPIs</brief_title>
  <official_title>A Bioequivalence Study to Assess the Systemic Exposure of Fluticasone Propionate and Salmeterol Administered as a Fixed Dose Combination From Different Dry Powder Inhalers in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mylan Pharma UK Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Viatris Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a crossover study to assess the systemic pharmacokinetics of fluticasone propionate&#xD;
      (FP) and salmeterol (SAL). Study medication will be administered as fixed dose combinations&#xD;
      (250 µg FP and 50 µg SAL) from the Advair® Diskus®, Seretide™ Accuhaler™ and CRC749 inhalers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study drug will be administered through the inhaled route to healthy subjects in single doses&#xD;
      (three inhalations, i.e. total dose 750 µg FP and 150 µg SAL).&#xD;
&#xD;
      Each subject will receive the following treatments in a random order:&#xD;
&#xD;
      A. MGR001 B. Seretide™ Accuhaler™ C. Advair® Diskus® There will be a wash out of 3 7 days&#xD;
      between treatment periods. Pharmacokinetics will be assessed by the measurement of plasma&#xD;
      concentrations of FP and SAL over the 48 hours following dosing. Adverse Events will be&#xD;
      collected throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2013</start_date>
  <completion_date type="Actual">November 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</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>AUC for each of the treatment groups FP/SAL</measure>
    <time_frame>3 days of each treatment period.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax for each of the treatment groups FP/SAL,</measure>
    <time_frame>3 days of each treatment period.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Day1 to Day3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inspiratory Flow assessments</measure>
    <time_frame>Day 1 pre-dose</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Asthma</condition>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>MGR001</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FP/SAL 250/50 µg 3 x inhalations (total dose 750/150 µg) administered via CRC749 inhaler.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Advair® Diskus®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FP/SAL 250/50 µg 3 x inhalations (total dose 750/150 µg) administered via Diskus® inhaler.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Seretide™ Accuhaler™</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FP/SAL 250/50 µg 3 x inhalations (total dose 750/150 µg) administered via Accuhaler™ inhaler.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MGR001</intervention_name>
    <description>Fluticasone Propionate is an inhaled corticosteroid (ICS) Salmeterol is a long acting β2 agonist (LABA)</description>
    <arm_group_label>MGR001</arm_group_label>
    <other_name>FP</other_name>
    <other_name>SAL</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Advair® Diskus®</intervention_name>
    <description>Fluticasone Propionate is an inhaled corticosteroid (ICS) Salmeterol is a long acting β2 agonist (LABA)</description>
    <arm_group_label>Advair® Diskus®</arm_group_label>
    <other_name>FP</other_name>
    <other_name>SAL</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Seretide™ Accuhaler™</intervention_name>
    <description>Fluticasone Propionate is an inhaled corticosteroid (ICS) Salmeterol is a long acting β2 agonist (LABA)</description>
    <arm_group_label>Seretide™ Accuhaler™</arm_group_label>
    <other_name>FP</other_name>
    <other_name>SAL</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male and/or female subjects between the ages of 18 and 55 years.&#xD;
&#xD;
          -  Body Mass Index (BMI) of 18 to 30.5 kg/m2; and a total body weight &gt;45 kg (99 lbs).&#xD;
&#xD;
          -  An informed consent document signed and dated by the subject.&#xD;
&#xD;
          -  Subjects who are willing and able to comply with scheduled visits, treatment plan,&#xD;
             laboratory tests, and other study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or&#xD;
             allergic disease (including drug allergies, but excluding untreated, asymptomatic,&#xD;
             seasonal allergies at the time of dosing).&#xD;
&#xD;
          -  A positive urine drug screen.&#xD;
&#xD;
          -  History of regular alcohol consumption exceeding 14 units/week for females or 21&#xD;
             units/week for males (1 unit = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer&#xD;
             or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.&#xD;
&#xD;
          -  Treatment with an investigational drug within 30 days or 5 half-lives or as determined&#xD;
             by the local requirement, whichever is longer, preceding the first dose of study&#xD;
             medication.&#xD;
&#xD;
          -  12-lead ECG demonstrating QTcF &gt;450 msec or a QRS interval &gt;120 msec at screening. If&#xD;
             QTcF exceeds 450 msec or QRS exceeds 120 msec, the ECG should be repeated two more&#xD;
             times and the average of the three QTcF or QRS values should be used to determine the&#xD;
             subject's eligibility.&#xD;
&#xD;
          -  Hemoglobin &lt;11.5 g/dL for female subjects or &lt;12.5 g/dL for male subjects.&#xD;
&#xD;
          -  Pregnant or nursing females; females of childbearing potential who are unwilling or&#xD;
             unable to use an acceptable method of contraception as outlined in this protocol.&#xD;
&#xD;
          -  Use of prescription or nonprescription drugs and dietary supplements within 7 days or&#xD;
             5 half lives (whichever is longer) prior to the first dose of study medication. Herbal&#xD;
             supplements must be discontinued at least 28 days prior to the first dose of study&#xD;
             medication. - Blood donation of approximately 1 pint (500 mL) or more within 56 days&#xD;
             prior to dosing.&#xD;
&#xD;
          -  Unwilling or unable to comply with the lifestyle guidelines described in this&#xD;
             protocol.&#xD;
&#xD;
          -  Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or&#xD;
             investigational product administration or may interfere with the interpretation of&#xD;
             study results.&#xD;
&#xD;
          -  Evidence or significant history of childhood or adult asthma, or any significant&#xD;
             history of wheeze, chronic cough, dyspnea at rest or acute bronchospasm.&#xD;
&#xD;
          -  Subjects with abnormal lung function tests at screening, defined as an FEV1 and/or FVC&#xD;
             which is &lt;80% of predicted.&#xD;
&#xD;
          -  Subjects who are current smokers. Ex-smokers who have given up smoking for &lt;6 months&#xD;
             and/or have a smoking pack history of ≥10 pack years.&#xD;
&#xD;
          -  Subjects with a lower respiratory tract infection in the 4 weeks prior to dosing.&#xD;
&#xD;
          -  History of sensitivity to lactose or sensitivity to the ingredients of&#xD;
             Advair®/Seretide™, including subjects with severe milk protein allergy in whom Advair®&#xD;
             is contraindicated.&#xD;
&#xD;
          -  Subject is the Investigator or a sub-Investigator, research assistant, pharmacist,&#xD;
             study coordinator, other staff, or a relative of any study personnel directly involved&#xD;
             with the conduct of the study.&#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>
  <overall_official>
    <last_name>Jon Ward</last_name>
    <role>Study Director</role>
    <affiliation>Mylan Pharma UK Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Worldwide Clinical Trials Early Phase Services</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>August 5, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>February 22, 2022</last_update_submitted>
  <last_update_submitted_qc>February 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fluticasone Propionate</keyword>
  <keyword>Salmeterol</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Healthy Subjects</keyword>
  <keyword>MGR001</keyword>
  <keyword>CRC749</keyword>
  <keyword>Dry Powder Inhaler</keyword>
  <keyword>generic</keyword>
  <keyword>Advair Diskus</keyword>
  <keyword>Seretide Accuhaler</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone-Salmeterol Drug Combination</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/NCT02215122
org study id: MGR001-1008
nct id: NCT02215122
lead sponsor: 
has dmc: No
This is a crossover study to assess the systemic pharmacokinetics of fluticasone propionate
      (FP) and salmeterol (SAL). Study medication will be administered as fixed dose combinations
      (250 µg FP and 50 µg SAL) from the Advair® Diskus®, Seretide™ Accuhaler™ and CRC749 inhalers.
Study drug will be administered through the inhaled route to healthy subjects in single doses
      (three inhalations, i.e. total dose 750 µg FP and 150 µg SAL).

      Each subject will receive the following treatments in a random order:

      A. MGR001 B. Seretide™ Accuhaler™ C. Advair® Diskus® There will be a wash out of 3 7 days
      between treatment periods. Pharmacokinetics will be assessed by the measurement of plasma
      concentrations of FP and SAL over the 48 hours following dosing. Adverse Events will be
      collected throughout the study.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC for each of the treatment groups FP/SAL
time frame: 3 days of each treatment period.
measure: Cmax for each of the treatment groups FP/SAL,
time frame: 3 days of each treatment period.
measure: Adverse events
time frame: Day1 to Day3
measure: Inspiratory Flow assessments
time frame: Day 1 pre-dose
arm group label: MGR001
arm group type: Experimental
description: FP/SAL 250/50 µg 3 x inhalations (total dose 750/150 µg) administered via CRC749 inhaler.
arm group label: Advair® Diskus®
arm group type: Experimental
description: FP/SAL 250/50 µg 3 x inhalations (total dose 750/150 µg) administered via Diskus® inhaler.
arm group label: Seretide™ Accuhaler™
arm group type: Experimental
description: FP/SAL 250/50 µg 3 x inhalations (total dose 750/150 µg) administered via Accuhaler™ inhaler.
intervention type: Drug
intervention name: MGR001
description: Fluticasone Propionate is an inhaled corticosteroid (ICS) Salmeterol is a long acting β2 agonist (LABA)
arm group label: MGR001
other name: FP
other name: SAL
intervention type: Drug
intervention name: Advair® Diskus®
description: Fluticasone Propionate is an inhaled corticosteroid (ICS) Salmeterol is a long acting β2 agonist (LABA)
arm group label: Advair® Diskus®
other name: FP
other name: SAL
intervention type: Drug
intervention name: Seretide™ Accuhaler™
description: Fluticasone Propionate is an inhaled corticosteroid (ICS) Salmeterol is a long acting β2 agonist (LABA)
arm group label: Seretide™ Accuhaler™
other name: FP
other name: SAL
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jon Ward
role: Study Director
affiliation: Mylan Pharma UK Ltd.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fluticasone-Salmeterol Drug Combination