<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/NCT02232087</url>
  </required_header>
  <id_info>
    <org_study_id>DDSD-1030-SAFL</org_study_id>
    <nct_id>NCT02232087</nct_id>
  </id_info>
  <brief_title>Single Blind Cross-over Dose Response Study in Subjects of Two Inhalers of Salmeterol and Fluticasone Propionate</brief_title>
  <official_title>Phase I Single Blind, Randomised, Cross-over Pharmacodynamic Dose Response Study in Healthy Volunteers of Two Pressurized Metered Dose Inhalers (pMDIs) That Deliver Salmeterol and Fluticasone Propionate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kindeva Drug Delivery</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kindeva Drug Delivery</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test the body's response to several doses of two different&#xD;
      inhalation products in healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Healthy subjects will be enrolled and will receive 2, 6, and 12 inhalations from both the&#xD;
      test and reference pMDI products according to a six-period cross-over design.&#xD;
      Electrocardiograms (ECGs) and plasma potassium and glucose levels will be measured pre-dose&#xD;
      and over 6 hours post-dose.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Relative Potency Max Heart Rate</measure>
    <time_frame>Baseline, up to 6 hrs</time_frame>
    <description>Selection of steepest part of dose response curve for Relative Potency: 6 and 12 inhalation dose pairs. Slope of B and C line compared with slope of E and F to obtain relative potency value. Two inhalation dose not utilized as not on steepest part of curve.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Relative Potency QTcB Interval</measure>
    <time_frame>Baseline up to 6 hrs</time_frame>
    <description>Selection of steepest part of dose response curve for Relative Potency: 2 and 6 inhalation dose pairs. Slope of A and B line compared with slope of D and E to obtain relative potency value. Twelve inhalation dose not utilized as not on steepest part of curve.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Max Heart Rate</measure>
    <time_frame>Baseline through 6 hours</time_frame>
    <description>max heart rate at the 2, 6, or 12 inhalations dose, assessed at multiple times over 6 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Potassium Level</measure>
    <time_frame>baseline through 6 hours</time_frame>
    <description>maximum plasma levels of potassium at 2, 6 or 12 inhalations dose inhalations dose, assessed a multiple times over 6 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Max Plasma Glucose Level</measure>
    <time_frame>baseline through 6 hours</time_frame>
    <description>maximum levels of glucose at the 2, 6 or 12 inhalations dose, assessed at multiple times over 6 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Max QTcB</measure>
    <time_frame>Baseline through 6 hours</time_frame>
    <description>For each dose, the 95% CIs for the mean difference for the test product versus the reference product were calculated.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>test product A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>salmeterol and fluticasone propionate, 2 puffs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>reference product D</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>salmeterol and fluticasone propionate, 2 puffs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>test product B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>salmeterol and fluticasone propionate, 6 puffs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>reference product E</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>salmeterol and fluticasone propionate, 6 puffs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>test product C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>salmeterol and fluticasone propionate, 12 puffs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>reference product F</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>salmeterol and fluticasone propionate, 12 puffs</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Salmeterol</intervention_name>
    <description>A, D 2 puffs; B, E 6 puffs; C, F 12 puffs</description>
    <arm_group_label>reference product D</arm_group_label>
    <arm_group_label>reference product E</arm_group_label>
    <arm_group_label>reference product F</arm_group_label>
    <arm_group_label>test product A</arm_group_label>
    <arm_group_label>test product B</arm_group_label>
    <arm_group_label>test product C</arm_group_label>
    <other_name>Sirdupla</other_name>
    <other_name>Seretide Evohaler</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fluticasone propionate</intervention_name>
    <description>A, D 2 puffs; B, E 6 puffs; C, F 12 puffs</description>
    <arm_group_label>reference product D</arm_group_label>
    <arm_group_label>reference product E</arm_group_label>
    <arm_group_label>reference product F</arm_group_label>
    <arm_group_label>test product A</arm_group_label>
    <arm_group_label>test product B</arm_group_label>
    <arm_group_label>test product C</arm_group_label>
    <other_name>Sirdupla</other_name>
    <other_name>Seretide Evohaler</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy Volunteer&#xD;
&#xD;
          -  Willing and able to give informed consent&#xD;
&#xD;
          -  Willing to withhold all alcoholic beverages for 48 hours and all xanthine- containing&#xD;
             foods and beverages for 24 hours prior to reporting to clinic&#xD;
&#xD;
          -  Male and female subjects aged 18 to 55 years (inclusive)&#xD;
&#xD;
          -  Subjects must agree to use an adequate method of contraception from admission through&#xD;
             12 weeks after last administration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence or history of clinically significant abnormalities or disease or chronic&#xD;
             respiratory disorders&#xD;
&#xD;
          -  Any presence or history of a clinically significant allergy including any adverse&#xD;
             reaction to study drug&#xD;
&#xD;
          -  History of drug or alcohol abuse within the past 2 years&#xD;
&#xD;
          -  Smoked tobacco within the past 6 months or have a history of more than 10- pack years&#xD;
             (number of packs smoked per day x number of years smoked)&#xD;
&#xD;
          -  Donation or loss of greater than 400 mL of blood within the previous 3 months&#xD;
&#xD;
          -  Have received any prescription medication within 4 weeks or investigational medication&#xD;
             within 12 weeks of study (exception: contraceptives are permitted)&#xD;
&#xD;
          -  Have received any non-prescription medication within 14 days prior to dosing&#xD;
             (exception: paracetamol use within 2 days)&#xD;
&#xD;
          -  Upper respiratory tract infection (excluding otitis media) within 14 days of the first&#xD;
             study day, or lower respiratory tract infection within the last 3 months&#xD;
&#xD;
          -  If female, nursing, lactating or pregnant&#xD;
&#xD;
          -  Regular alcohol consumption in males &gt;21 units per week and females &gt;14 units per week&#xD;
             (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)&#xD;
&#xD;
          -  Surgery scheduled during the study or within 3 weeks after last dose&#xD;
&#xD;
          -  History of familial long QT syndrome or history of sudden death in family members aged&#xD;
             &lt; 30 years&#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>Pui Leung, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Quotient Clinical Ltd</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Quotient Clinical Ltd</name>
      <address>
        <city>Ruddington</city>
        <state>Nottingham</state>
        <zip>NG11 6JS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <results_reference>
    <citation>Harrison LI, Sessions V, Wiggenhorn CJ, Chalmers D, Leung P, Efthimiou J. Comparison of systemic pharmacodynamic effects of two combination pressurized metered dose inhalers that deliver salmeterol and fluticasone propionate. Br J Clin Pharmacol. 2017 Nov;83(11):2377-2385. doi: 10.1111/bcp.13349. Epub 2017 Aug 1.</citation>
    <PMID>28626983</PMID>
  </results_reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 2, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <results_first_submitted>February 4, 2016</results_first_submitted>
  <results_first_submitted_qc>October 29, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 2, 2020</results_first_posted>
  <last_update_submitted>June 13, 2022</last_update_submitted>
  <last_update_submitted_qc>June 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>long-acting beta agonist (LABA)</keyword>
  <keyword>corticosteroid</keyword>
  <keyword>pMDI</keyword>
  <keyword>inhaler</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Xhance</mesh_term>
    <mesh_term>Salmeterol Xinafoate</mesh_term>
    <mesh_term>Fluticasone-Salmeterol Drug Combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment began 07 July 2014</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Sequence 1 (A, F, B, E, C, D)</title>
          <description>salmeterol and fluticasone propionate per inhalation&#xD;
A = 2 inhalations (test product), B = 6 inhalations (test product), C = 12 inhalations (test product), D = 2 inhalations (reference product), E = 6 inhalations (reference product) and F = 12 inhalations (reference product)</description>
        </group>
        <group group_id="P2">
          <title>Sequence 2 (B, A, C, F, D, E)</title>
          <description>salmeterol and fluticasone propionate per inhalation&#xD;
A = 2 inhalations (test product), B = 6 inhalations (test product), C = 12 inhalations (test product), D = 2 inhalations (reference product), E = 6 inhalations (reference product) and F = 12 inhalations (reference product)</description>
        </group>
        <group group_id="P3">
          <title>Sequence 3 (C, B, D, A, E, F)</title>
          <description>salmeterol and fluticasone propionate per inhalation&#xD;
A = 2 inhalations (test product), B = 6 inhalations (test product), C = 12 inhalations (test product), D = 2 inhalations (reference product), E = 6 inhalations (reference product) and F = 12 inhalations (reference product)</description>
        </group>
        <group group_id="P4">
          <title>Sequence 4 (D, C, E, B, F, A)</title>
          <description>salmeterol and fluticasone propionate per inhalation&#xD;
A = 2 inhalations (test product), B = 6 inhalations (test product), C = 12 inhalations (test product), D = 2 inhalations (reference product), E = 6 inhalations (reference product) and F = 12 inhalations (reference product)</description>
        </group>
        <group group_id="P5">
          <title>Sequence 5 (E, D, F, C, A, B)</title>
          <description>salmeterol and fluticasone propionate per inhalation&#xD;
A = 2 inhalations (test product), B = 6 inhalations (test product), C = 12 inhalations (test product), D = 2 inhalations (reference product), E = 6 inhalations (reference product) and F = 12 inhalations (reference product)</description>
        </group>
        <group group_id="P6">
          <title>Sequence 6 (F, E, A, D, B, C )</title>
          <description>salmeterol and fluticasone propionate per inhalation&#xD;
A = 2 inhalations (test product), B = 6 inhalations (test product), C = 12 inhalations (test product), D = 2 inhalations (reference product), E = 6 inhalations (reference product) and F = 12 inhalations (reference product)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="8"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="7"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>poor inhalation technique</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>protocol stop criteria</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>all subjects who received at least one test and one reference product for same dose</population>
      <group_list>
        <group group_id="B1">
          <title>All Subjects</title>
          <description>salmeterol and fluticasone propionate</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="52"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>age range of 18 to 55 years inclusive</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.5" spread="10.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.6" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>forced expiratory volume at one second</title>
          <description>forced expiratory volume at one second &gt; 85% predicted</description>
          <units>% predicted normal</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="101.19" spread="10.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Relative Potency Max Heart Rate</title>
        <description>Selection of steepest part of dose response curve for Relative Potency: 6 and 12 inhalation dose pairs. Slope of B and C line compared with slope of E and F to obtain relative potency value. Two inhalation dose not utilized as not on steepest part of curve.</description>
        <time_frame>Baseline, up to 6 hrs</time_frame>
        <population>relative potency calculated for dose pairs B (6 inhalations) and C (12 inhalations), compared with E (6 inhalations) and F (12 inhalations)</population>
        <group_list>
          <group group_id="O1">
            <title>Test B and C vs Reference E and F</title>
            <description>salmeterol and fluticasone propionate&#xD;
Salmeterol: B, E 6 puffs; C, F 12 puffs&#xD;
fluticasone propionate: B, E 6 puffs; C, F 12 puffs</description>
          </group>
        </group_list>
        <measure>
          <title>Relative Potency Max Heart Rate</title>
          <description>Selection of steepest part of dose response curve for Relative Potency: 6 and 12 inhalation dose pairs. Slope of B and C line compared with slope of E and F to obtain relative potency value. Two inhalation dose not utilized as not on steepest part of curve.</description>
          <population>relative potency calculated for dose pairs B (6 inhalations) and C (12 inhalations), compared with E (6 inhalations) and F (12 inhalations)</population>
          <units>unitless</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8619" lower_limit="0.7209" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The measurement of relative potency was conducted for the pair of doses which met the above criteria and lay on the steepest linear portion of the dose response curve. The log estimate of relative potency was obtained as the ratio of the estimated treatment effect as measured by the difference in the intercepts of the parallel lines divided by the estimate of the common slope for log dose.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The potency of the test and reference product was considered equivalent if the 90% CI for the estimate of relative potency was completely contained within the limits of 0.67 to 1.50</non_inferiority_desc>
            <p_value>&gt;0.10</p_value>
            <p_value_desc>test for parallelism of dose response lines</p_value_desc>
            <method>ANOVA</method>
            <param_type>Odds Ratio, log</param_type>
            <param_value>1.00</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.67</ci_lower_limit>
            <ci_upper_limit>1.50</ci_upper_limit>
            <estimate_desc>Test is the numerator</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Relative Potency QTcB Interval</title>
        <description>Selection of steepest part of dose response curve for Relative Potency: 2 and 6 inhalation dose pairs. Slope of A and B line compared with slope of D and E to obtain relative potency value. Twelve inhalation dose not utilized as not on steepest part of curve.</description>
        <time_frame>Baseline up to 6 hrs</time_frame>
        <population>relative potency calculated for dose pairs A (2 inhalations) and B (6 inhalations), compared with D (2 inhalations) and E (6 inhalations)</population>
        <group_list>
          <group group_id="O1">
            <title>Test A and B vs Reference D and E</title>
            <description>salmeterol and fluticasone propionate&#xD;
Salmeterol: A, D 2 puffs; B, E 6 puffs&#xD;
fluticasone propionate: A, D 2 puffs; B, E 6 puffs</description>
          </group>
        </group_list>
        <measure>
          <title>Relative Potency QTcB Interval</title>
          <description>Selection of steepest part of dose response curve for Relative Potency: 2 and 6 inhalation dose pairs. Slope of A and B line compared with slope of D and E to obtain relative potency value. Twelve inhalation dose not utilized as not on steepest part of curve.</description>
          <population>relative potency calculated for dose pairs A (2 inhalations) and B (6 inhalations), compared with D (2 inhalations) and E (6 inhalations)</population>
          <units>unitless</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0760" lower_limit="0.8206" upper_limit="1.4238"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The measurement of relative potency was conducted for the pair of doses which met the above criteria and lay on the steepest linear portion of the dose response curve. The log estimate of relative potency was obtained as the ratio of the estimated treatment effect as measured by the difference in the intercepts of the parallel lines divided by the estimate of the common slope for log dose.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The potency of the test and reference product was considered equivalent if the 90% CI for the estimate of relative potency was completely contained within the limits of 0.67 to 1.50</non_inferiority_desc>
            <p_value>&gt;0.10</p_value>
            <p_value_desc>test for parallelism of dose response lines</p_value_desc>
            <method>ANOVA</method>
            <param_type>Odds Ratio, log</param_type>
            <param_value>1.00</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.67</ci_lower_limit>
            <ci_upper_limit>1.50</ci_upper_limit>
            <estimate_desc>Test is the numerator</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Max Heart Rate</title>
        <description>max heart rate at the 2, 6, or 12 inhalations dose, assessed at multiple times over 6 hours</description>
        <time_frame>Baseline through 6 hours</time_frame>
        <population>subjects who received the test and the reference product at the 2, 6, or 12 inhalations dose</population>
        <group_list>
          <group group_id="O1">
            <title>Test Product A</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 2 inhalations&#xD;
fluticasone propionate: 2 inhalations</description>
          </group>
          <group group_id="O2">
            <title>Reference Product D</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 2 inhalations&#xD;
fluticasone propionate: 2 inhalations</description>
          </group>
          <group group_id="O3">
            <title>Test Product B</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 6 inhalations&#xD;
fluticasone propionate: 6 inhalations</description>
          </group>
          <group group_id="O4">
            <title>Reference Product E</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 6 inhalations&#xD;
fluticasone propionate: 6 inhalations</description>
          </group>
          <group group_id="O5">
            <title>Test Product C</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 12 inhalations&#xD;
fluticasone propionate: 12 inhalations</description>
          </group>
          <group group_id="O6">
            <title>Reference Product F</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate):12 inhalations&#xD;
fluticasone propionate: 12 inhalations</description>
          </group>
        </group_list>
        <measure>
          <title>Max Heart Rate</title>
          <description>max heart rate at the 2, 6, or 12 inhalations dose, assessed at multiple times over 6 hours</description>
          <population>subjects who received the test and the reference product at the 2, 6, or 12 inhalations dose</population>
          <units>bpm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="43"/>
                <count group_id="O3" value="45"/>
                <count group_id="O4" value="45"/>
                <count group_id="O5" value="44"/>
                <count group_id="O6" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.1" spread="10.9"/>
                    <measurement group_id="O2" value="65.5" spread="10.1"/>
                    <measurement group_id="O3" value="68.9" spread="11.0"/>
                    <measurement group_id="O4" value="69.9" spread="12.2"/>
                    <measurement group_id="O5" value="75.3" spread="13.3"/>
                    <measurement group_id="O6" value="76.8" spread="14.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.55</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.5</ci_lower_limit>
            <ci_upper_limit>1.4</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.53</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.5</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.011</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.5</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Potassium Level</title>
        <description>maximum plasma levels of potassium at 2, 6 or 12 inhalations dose inhalations dose, assessed a multiple times over 6 hours.</description>
        <time_frame>baseline through 6 hours</time_frame>
        <population>subjects who received both the test and reference products at the 2, 6, or 12 inhalations dose</population>
        <group_list>
          <group group_id="O1">
            <title>Test Product A</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 2, 6, and 12 inhalations&#xD;
fluticasone propionate: 2 inhalations</description>
          </group>
          <group group_id="O2">
            <title>Reference Product D</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 2 inhalations&#xD;
fluticasone propionate: 2 inhalations</description>
          </group>
          <group group_id="O3">
            <title>Test Product B</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 6 inhalations&#xD;
fluticasone propionate: 6 inhalations</description>
          </group>
          <group group_id="O4">
            <title>Reference Product E</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 6 inhalations&#xD;
fluticasone propionate: 6 inhalations</description>
          </group>
          <group group_id="O5">
            <title>Test Product C</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 12 inhalations&#xD;
fluticasone propionate: 12 inhalations</description>
          </group>
          <group group_id="O6">
            <title>Reference Product F</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 12 inhalations&#xD;
fluticasone propionate: 12 inhalations</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Potassium Level</title>
          <description>maximum plasma levels of potassium at 2, 6 or 12 inhalations dose inhalations dose, assessed a multiple times over 6 hours.</description>
          <population>subjects who received both the test and reference products at the 2, 6, or 12 inhalations dose</population>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="43"/>
                <count group_id="O3" value="45"/>
                <count group_id="O4" value="45"/>
                <count group_id="O5" value="44"/>
                <count group_id="O6" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.82" spread="0.19"/>
                    <measurement group_id="O2" value="3.78" spread="0.16"/>
                    <measurement group_id="O3" value="3.76" spread="0.20"/>
                    <measurement group_id="O4" value="3.75" spread="0.19"/>
                    <measurement group_id="O5" value="3.63" spread="0.24"/>
                    <measurement group_id="O6" value="3.61" spread="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.26</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.03</ci_lower_limit>
            <ci_upper_limit>0.10</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.93</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.06</ci_lower_limit>
            <ci_upper_limit>0.06</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.48</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.04</ci_lower_limit>
            <ci_upper_limit>0.08</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Max Plasma Glucose Level</title>
        <description>maximum levels of glucose at the 2, 6 or 12 inhalations dose, assessed at multiple times over 6 hours.</description>
        <time_frame>baseline through 6 hours</time_frame>
        <population>subjects who received both the test and reference products at the two inhalations dose</population>
        <group_list>
          <group group_id="O1">
            <title>Test Product A</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 2 inhalations&#xD;
fluticasone propionate: 2 inhalations</description>
          </group>
          <group group_id="O2">
            <title>Reference Product D</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 2 inhalations&#xD;
fluticasone propionate: 2 inhalations</description>
          </group>
          <group group_id="O3">
            <title>Test Product B</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 6 inhalations&#xD;
fluticasone propionate: 6 inhalations</description>
          </group>
          <group group_id="O4">
            <title>Reference Product E</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 6 inhalations&#xD;
fluticasone propionate: 6 inhalations</description>
          </group>
          <group group_id="O5">
            <title>Test Product C</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 12 inhalations&#xD;
fluticasone propionate: 12 inhalations</description>
          </group>
          <group group_id="O6">
            <title>Reference Product F</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 12 inhalations&#xD;
fluticasone propionate: 12 inhalations</description>
          </group>
        </group_list>
        <measure>
          <title>Max Plasma Glucose Level</title>
          <description>maximum levels of glucose at the 2, 6 or 12 inhalations dose, assessed at multiple times over 6 hours.</description>
          <population>subjects who received both the test and reference products at the two inhalations dose</population>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="43"/>
                <count group_id="O3" value="45"/>
                <count group_id="O4" value="45"/>
                <count group_id="O5" value="44"/>
                <count group_id="O6" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.31" spread="0.49"/>
                    <measurement group_id="O2" value="5.31" spread="0.40"/>
                    <measurement group_id="O3" value="5.53" spread="0.65"/>
                    <measurement group_id="O4" value="5.62" spread="0.54"/>
                    <measurement group_id="O5" value="5.88" spread="0.66"/>
                    <measurement group_id="O6" value="5.98" spread="0.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.93</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.42</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.224</ci_lower_limit>
            <ci_upper_limit>0.093</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.078</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.302</ci_lower_limit>
            <ci_upper_limit>0.016</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Max QTcB</title>
        <description>For each dose, the 95% CIs for the mean difference for the test product versus the reference product were calculated.</description>
        <time_frame>Baseline through 6 hours</time_frame>
        <population>all subjects who received the test and the reference product at the two inhalations dose</population>
        <group_list>
          <group group_id="O1">
            <title>Test Product A</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 2 inhalations&#xD;
fluticasone propionate: 2 inhalations</description>
          </group>
          <group group_id="O2">
            <title>Reference Product D</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 2 inhalations&#xD;
fluticasone propionate: 2 inhalations</description>
          </group>
          <group group_id="O3">
            <title>Test Product B</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 6 inhalations&#xD;
fluticasone propionate: 6 inhalations</description>
          </group>
          <group group_id="O4">
            <title>Reference Product E</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 6 inhalations&#xD;
fluticasone propionate: 6 inhalations</description>
          </group>
          <group group_id="O5">
            <title>Test Product D</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 12 inhalations&#xD;
fluticasone propionate: 12 inhalations</description>
          </group>
          <group group_id="O6">
            <title>Reference Product F</title>
            <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 12 inhalations&#xD;
fluticasone propionate: 12 inhalations</description>
          </group>
        </group_list>
        <measure>
          <title>Max QTcB</title>
          <description>For each dose, the 95% CIs for the mean difference for the test product versus the reference product were calculated.</description>
          <population>all subjects who received the test and the reference product at the two inhalations dose</population>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="43"/>
                <count group_id="O3" value="45"/>
                <count group_id="O4" value="45"/>
                <count group_id="O5" value="44"/>
                <count group_id="O6" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="422.3" spread="22.4"/>
                    <measurement group_id="O2" value="422.1" spread="23.7"/>
                    <measurement group_id="O3" value="430.0" spread="23.1"/>
                    <measurement group_id="O4" value="430.2" spread="21.4"/>
                    <measurement group_id="O5" value="441.0" spread="20.5"/>
                    <measurement group_id="O6" value="444.0" spread="26.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.71</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.9</ci_lower_limit>
            <ci_upper_limit>5.7</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>1.00</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.7</ci_lower_limit>
            <ci_upper_limit>4.7</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>For each dose, the 95% CIs for the mean differences for the test product versus the reference product were calculated.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Comparability confirmed if confidence interval includes zero.</non_inferiority_desc>
            <p_value>0.016</p_value>
            <p_value_desc>Comparability demonstrated for p&gt;0.05</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.6</ci_lower_limit>
            <ci_upper_limit>-1.1</ci_upper_limit>
            <estimate_desc>Comparability confirmed if confidence interval includes zero.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected for up to 2 months for each subject. The duration of the clinical phase of the study was 4 months.</time_frame>
      <desc>All subjects who received a dose of at least one product</desc>
      <group_list>
        <group group_id="E1">
          <title>Test Product A</title>
          <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 2 inhalations&#xD;
fluticasone propionate: 2 inhalations</description>
        </group>
        <group group_id="E2">
          <title>Test Product B</title>
          <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 6 inhalations&#xD;
fluticasone propionate: 6 inhalations</description>
        </group>
        <group group_id="E3">
          <title>Test Product C</title>
          <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 12 inhalations&#xD;
fluticasone propionate: 12 inhalations</description>
        </group>
        <group group_id="E4">
          <title>Reference Product D</title>
          <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 6 inhalations&#xD;
fluticasone propionate: 6 inhalations</description>
        </group>
        <group group_id="E5">
          <title>Reference Product E</title>
          <description>salmeterol and fluticasone propionate&#xD;
salmeterol (as salmeterol xinafoate): 12 inhalations&#xD;
fluticasone propionate: 12 inhalations</description>
        </group>
        <group group_id="E6">
          <title>Referencet Product F</title>
          <description>salmeterol and fluticasone propionate</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="8" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="8" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Sinus Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Mouth Ulceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Feeling Hot</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Feeling Cold</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>URTI</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ECG QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Prolongation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Heart Rate increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Paraesthesia Oral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Nervousness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Rhinorrtoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="48"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The sponsor reserves the right to the first publication of the results. Following the first publication, or if the sponsor confirms in writing no interest in publishing the results, Quotient Clinical Ltd or the Principal Investigator may proceed to publish results from the study, giving the sponsor 60 days to review the manuscript.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>There are no limitations or caveats.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Pui Leung</name_or_title>
      <organization>Quotient Clinical Ltd</organization>
      <phone>44(0)115 974 9000</phone>
      <email>Pui Leung &lt;Pui.Leung@quotientclinical.com&gt;</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02232087
org study id: DDSD-1030-SAFL
nct id: NCT02232087
lead sponsor: 
has dmc: Yes
The purpose of this study is to test the body's response to several doses of two different
      inhalation products in healthy volunteers.
Healthy subjects will be enrolled and will receive 2, 6, and 12 inhalations from both the
      test and reference pMDI products according to a six-period cross-over design.
      Electrocardiograms (ECGs) and plasma potassium and glucose levels will be measured pre-dose
      and over 6 hours post-dose.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Relative Potency Max Heart Rate
time frame: Baseline, up to 6 hrs
description: Selection of steepest part of dose response curve for Relative Potency: 6 and 12 inhalation dose pairs. Slope of B and C line compared with slope of E and F to obtain relative potency value. Two inhalation dose not utilized as not on steepest part of curve.
measure: Relative Potency QTcB Interval
time frame: Baseline up to 6 hrs
description: Selection of steepest part of dose response curve for Relative Potency: 2 and 6 inhalation dose pairs. Slope of A and B line compared with slope of D and E to obtain relative potency value. Twelve inhalation dose not utilized as not on steepest part of curve.
measure: Max Heart Rate
time frame: Baseline through 6 hours
description: max heart rate at the 2, 6, or 12 inhalations dose, assessed at multiple times over 6 hours
measure: Plasma Potassium Level
time frame: baseline through 6 hours
description: maximum plasma levels of potassium at 2, 6 or 12 inhalations dose inhalations dose, assessed a multiple times over 6 hours.
measure: Max Plasma Glucose Level
time frame: baseline through 6 hours
description: maximum levels of glucose at the 2, 6 or 12 inhalations dose, assessed at multiple times over 6 hours.
measure: Max QTcB
time frame: Baseline through 6 hours
description: For each dose, the 95% CIs for the mean difference for the test product versus the reference product were calculated.
arm group label: test product A
arm group type: Experimental
description: salmeterol and fluticasone propionate, 2 puffs
arm group label: reference product D
arm group type: Active Comparator
description: salmeterol and fluticasone propionate, 2 puffs
arm group label: test product B
arm group type: Experimental
description: salmeterol and fluticasone propionate, 6 puffs
arm group label: reference product E
arm group type: Active Comparator
description: salmeterol and fluticasone propionate, 6 puffs
arm group label: test product C
arm group type: Experimental
description: salmeterol and fluticasone propionate, 12 puffs
arm group label: reference product F
arm group type: Active Comparator
description: salmeterol and fluticasone propionate, 12 puffs
intervention type: Drug
intervention name: Salmeterol
description: A, D 2 puffs; B, E 6 puffs; C, F 12 puffs
arm group label: reference product D
arm group label: reference product E
arm group label: reference product F
arm group label: test product A
arm group label: test product B
arm group label: test product C
other name: Sirdupla
other name: Seretide Evohaler
intervention type: Drug
intervention name: fluticasone propionate
description: A, D 2 puffs; B, E 6 puffs; C, F 12 puffs
arm group label: reference product D
arm group label: reference product E
arm group label: reference product F
arm group label: test product A
arm group label: test product B
arm group label: test product C
other name: Sirdupla
other name: Seretide Evohaler
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pui Leung, MD
role: Principal Investigator
affiliation: Quotient Clinical Ltd
facility: 
country: United Kingdom
citation: Harrison LI, Sessions V, Wiggenhorn CJ, Chalmers D, Leung P, Efthimiou J. Comparison of systemic pharmacodynamic effects of two combination pressurized metered dose inhalers that deliver salmeterol and fluticasone propionate. Br J Clin Pharmacol. 2017 Nov;83(11):2377-2385. doi: 10.1111/bcp.13349. Epub 2017 Aug 1.
PMID: 28626983
responsible party type: Sponsor
mesh term: Fluticasone
mesh term: Xhance
mesh term: Salmeterol Xinafoate
mesh term: Fluticasone-Salmeterol Drug Combination
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: There are no limitations or caveats.
point of contact: 