<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/NCT01687283</url>
  </required_header>
  <id_info>
    <org_study_id>114219</org_study_id>
    <nct_id>NCT01687283</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of Fluticasone Proponate Inhalation Solution in Adult and Adolescent Asthma</brief_title>
  <official_title>A Multicenter, Randomized, Single Blind, Active Controlled, Parallel Group Study to Determine Efficacy and Safety of Nebulized Fluticasone Propionate 1mg BID Compared With Nebulized Budesonide 2mg BID Administered for 12 Weeks in Chinese Adult and Adolescent Patients With Severe Persistent Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicentre, randomized, single-blind, active-controlled, parallel-group phase III&#xD;
      local registration study for a treatment period of 12 weeks. This study aims to assess the&#xD;
      effectiveness and safety of fluticasone propionate 1mg via nebulizer BID in treatment of&#xD;
      Chinese adult and adolescent patients with severe persistent asthma for a treatment period of&#xD;
      12 weeks versus budesonide 2mg via nebulizer BID. The steady-state plasma pharmacokinetics of&#xD;
      fluticasone propionate inhalation solution will also be assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Male or female subjects between 17 to 70 (inclusive) years of age with severe persistent&#xD;
      asthma meeting the inclusion criteria and having completed the screening period of 2 weeks&#xD;
      will, in a proportion of 1:1, randomly receive fluticasone propionate 1mg via nebulizer BID&#xD;
      or budesonide 2mg via nebulizer BID for a treatment period of 12 weeks. The clinic visit will&#xD;
      be arranged at 2 weeks, 4 weeks, 8 weeks and 12 weeks during study treatment. If the subjects&#xD;
      meet the criteria of pre-defined asthma control at treatment 4 weeks or 8 weeks, they will&#xD;
      have one chance to be treated with the half dose of study drug. 2 weeks after completion of&#xD;
      study treatment or after early withdrawal from study, the follow-up visit will be performed&#xD;
      to assess the post-treatment adverse events. The primary endpoint is the mean change from&#xD;
      baseline in morning peak expiratory flow (PEF) over the 12 week treatment period. Safety&#xD;
      assessments include adverse events, vital signs, oral and oropharyngeal candidiasis,&#xD;
      hematological, biochemical tests), 24-hour urinary cortisol and 12-lead ECG. The steady-state&#xD;
      plasma pharmacokinetics of fluticasone propionate inhalation solution will also be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 27, 2012</start_date>
  <completion_date type="Actual">November 7, 2013</completion_date>
  <primary_completion_date type="Actual">November 7, 2013</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline (Day 1 of Treatment Period/Visit 2) in Morning Peak Expiratory Flow (AM PEF) Over 12 Weeks in Intent-to-treat Population</measure>
    <time_frame>Baseline (Visit 2) and up to Week 12</time_frame>
    <description>The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis was performed using analysis of covariance (ANCOVA) model. Abbreviations used in statistical analysis section: standard deviation (SD) and significance (sig)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline (Day 1 of Trt Period/Visit 2) in AM PEF Over 12 Weeks in Per Protocol Population</measure>
    <time_frame>Baseline (Visit 2) and up to Week 12</time_frame>
    <description>The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis was performed using analysis of covariance (ANCOVA) model.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change of Evening PEF From Baseline Over 12 Weeks</measure>
    <time_frame>Baseline (Visit 2) and up to Week 12</time_frame>
    <description>The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the evening PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily PM PEF averaged over the 12-weeks treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Percentage of Symptom-free 24-hour Periods From Baseline Over 12 Weeks</measure>
    <time_frame>Baseline (Visit 2) and over 12 Weeks</time_frame>
    <description>While calculating symptom-free 24-hour periods, a given 24-hour period was set to be &quot;symptom free&quot; only if the participant's responses to both the morning and evening assessments indicated no symptoms. The Baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. Change from Baseline was calculated as the difference between the value of the endpoint at the time point of interest and the baseline value. The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Day-time and Night-time Symptom Scores Per Participant Over 12 Weeks</measure>
    <time_frame>Over 12 Weeks</time_frame>
    <description>Participants recorded day-time symptom score every day in the morning and evening at bedtime before taking any rescue or study medication and before PEF measurement, using 6 point scale on Diary Card indicating 0 = No symptoms during the day and 5 =Symptoms so severe that participant could not go to work or perform normal daily activities. Night time symptoms were scored while waking in the morning on a scale of 0 (no symptoms) to 4 (severe). The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Percentage of Rescue-free 24-hour Periods From Baseline Over 12 Weeks</measure>
    <time_frame>Baseline and over 12 weeks</time_frame>
    <description>While calculating rescue-free 24-hour periods, the 24-hour period was only set to be &quot;rescue free&quot; if responses to both the morning and evening, assessments indicated no use of rescue medication. If there were symptoms in either the morning or the evening then that 24-hour period was set to as &quot;not symptom free&quot;. Similarly, if there was rescue medication use in either the morning or the evening, then that 24-hour period was set to as &quot;not rescue free&quot;. The Baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Number of Times Rescue Medication Use Over 12 Weeks</measure>
    <time_frame>Up to week 12</time_frame>
    <description>Participants recorded the number of inhalations of rescue salbutamol inhalation aerosol used during the day and night. The baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. The analysis only included participants who had at least 2 days of non-missing numbers of times rescue medication (including zero) after randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of Clinical Lung Function Measurement Forced Expiratory Volume in One Second (FEV1) From Baseline Over 12 Weeks</measure>
    <time_frame>Baseline and at Week 2, 4, 8 and 12</time_frame>
    <description>FEV1 as a measure of lung function assessment was measured at Week 2, 4, 8 and 12. FEV1 measures were performed electronically by spirometry. The highest of three technically acceptable measurements was recorded. FEV1 was measured prior to study drug administration and any rescue salbutamol use. Baseline value was the assessment at Visit 2.Change from baseline was calculated as the value at the specific time point minus baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution- Time to Maximum Observed Plasma Concentration (Tmax)</measure>
    <time_frame>Pre-dose, 0.5 hour (h), 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2</time_frame>
    <description>Tmax is defined as the time to maximum observed plasma concentration. Blood Pharmacokinetic (PK) samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of the last dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2</time_frame>
    <description>Cmax was defined as maximum observed plasma concentration. Blood PK samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of last dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-area Under the Plasma Concentration-time Curve for the Dose Interval [AUC (0-τ)]</measure>
    <time_frame>Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2</time_frame>
    <description>AUC (0-τ) was defined as the area under the plasma concentration-time curve for the dose interval. Blood PK samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of last dose.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">316</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>fluticasone propionate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 mg BID inhalation via nebulizer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>budesonide suspension</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2 mg BID inhalation via nebulizer</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fluticasone propionate inhalation solution</intervention_name>
    <description>1 mg BID inhalation for 12 weeks with one possible chance to change to 0.5 mg BID</description>
    <arm_group_label>fluticasone propionate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>budesonide suspension</intervention_name>
    <description>2 mg BID inhalation for 12 weeks with one possible chance to change to 1 mg BID</description>
    <arm_group_label>budesonide suspension</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chinese male or female outpatients aged &gt;=17 years and &lt;=70 years&#xD;
&#xD;
          -  A female is eligible to enter and participate in this study if she is:&#xD;
&#xD;
        Non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including&#xD;
        any female who is pre-menarchal, post-menopausal), or Child-bearing potential, has a&#xD;
        negative urinary pregnancy test at screening and agrees to take contraceptive precautions&#xD;
        (including abstinence) (referring to appendix 1: Highly Effective Methods For Avoidance Of&#xD;
        Pregnancy In Women Of Childbearing Potential) which, in the opinion of the investigator are&#xD;
        adequate to prevent pregnancy during the study.&#xD;
&#xD;
          -  A documented clinical history of asthma for a period of at least 12 weeks prior to&#xD;
             Visit 1 based on the Guidance of Asthma Management and Prevention 2008 in China (refer&#xD;
             to appendix 2).&#xD;
&#xD;
          -  Demonstrated &gt;=12% and &gt;=200mL reversibility of FEV1 within 15-30minutes following&#xD;
             inhalation of 200-400ug of salbutamol aerosol within 12 months prior to visit 1 or at&#xD;
             the Screening Visit.&#xD;
&#xD;
          -  Subjects have pre-bronchodilator FEV1% predicted between &gt;=40% and &lt;80% at visit 1.&#xD;
&#xD;
          -  Subjects on a stable dose at least 2 weeks with high dose ICS (eg. Fluticasone&#xD;
             Propionate 500ug twice daily or other ICS with equivalence doses, refer to Appendix 3)&#xD;
             or moderate dose ICS plus LABA (eg. Fluticasone Propionate/Salmoterol 250/50ug , twice&#xD;
             daily; or Budesonide/Formoterol Fumarate in maintainance160/4.5ug, two inhalation,&#xD;
             twice daily; or other product equivalence doses).&#xD;
&#xD;
          -  Subjects and/or their legally acceptable representative (if applicable) is willing to&#xD;
             give informed consent to participate in the study, and having ability to comply with&#xD;
             study procedures (including patients can use Nebulizer correctly, be able to&#xD;
             understand and complete the diary cards and be able to record their PEF using a peak&#xD;
             flow meter). The subjects and/or their legally acceptable representative (if&#xD;
             applicable) will need to give additional informed consent to be eligible for blood&#xD;
             pharmacokinetic samplings.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of Life-threatening asthma: Defined for this protocol as an asthma episode&#xD;
             that required intubation and/or was associated with hypercapnea, respiratory arrest or&#xD;
             hypoxic seizures.&#xD;
&#xD;
          -  Bacterial or viral infection of the upper or lower respiratory tract, sinus or middle&#xD;
             ear that is not resolved within 4 weeks of visit 1 and led to a change in asthma&#xD;
             management or, in the opinion of the investigator, is expected to affect the subject's&#xD;
             asthma status or the subject's ability to participate in the study.&#xD;
&#xD;
          -  A subject must not have current evidence of pneumonia, pneumothorax, atelectasis,&#xD;
             pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema,&#xD;
             chronic obstructive pulmonary disease, or other respiratory abnormalities other than&#xD;
             asthma.&#xD;
&#xD;
          -  Subjects have any clinically significant, uncontrolled condition or disease state&#xD;
             that, in the opinion of the investigator, would put the safety of the patient at risk&#xD;
             through study participation or would confound the interpretation of the efficacy&#xD;
             results if the condition/disease exacerbated during the study.&#xD;
&#xD;
          -  Subjects will not b eligible for the run-in if he/she has clinical visual evidence of&#xD;
             candidias at visit 1.&#xD;
&#xD;
          -  Current smoker or a smoking history of 10 pack years or more. A subject may not have&#xD;
             used inhaled tobacco products (i.e., cigarettes, cigars or pipe tobacco) within the&#xD;
             past 3 months.&#xD;
&#xD;
          -  Patients who are pregnant or lactating.&#xD;
&#xD;
          -  Patients having any known or suspected hypersensitivity to corticosteroids or the&#xD;
             excipients of study drug, including Polysorbate 20, Sorbitan monolaurate, Monosodium&#xD;
             phosphate dehydrate, Dibasic sodium phosphate anhydrous, Sodium Chloride and Water for&#xD;
             Injection.&#xD;
&#xD;
          -  Patients who have evidence of alcohol abuse.&#xD;
&#xD;
          -  Patients who will have a pre-planned surgery operation in 6 months.&#xD;
&#xD;
          -  Liver function tests: aspartate aminotransferase (AST) / alanine aminotransferase&#xD;
             (ALT) &gt;= 2 × upper limit of normal (ULN) or alkaline phosphatase (ALP) / bilirubin&#xD;
             &gt;1.5 × ULN (isolated bilirubin &gt;1.5 × ULN is acceptable if bilirubin is fractionated&#xD;
             and direct bilirubin &lt;35%).&#xD;
&#xD;
          -  Has QTc &gt;= 450 msec or &gt;= 480 msec for patients with bundle branch block at the time&#xD;
             of screening.&#xD;
&#xD;
          -  A subject will not be eligible for this study if he/she is an immediate family member&#xD;
             of the participating Investigator, sub Investigator, study coordinator, or employee of&#xD;
             the participating Investigator.&#xD;
&#xD;
          -  No subject is permitted to perform night shift work from Visit 1 until completion of&#xD;
             the study treatment period.&#xD;
&#xD;
          -  Use of the following medications within the following time intervals prior to visit 1&#xD;
             or during the study: Medication / No use within the following time intervals prior to&#xD;
             Screening (Visit 1) or at any time during the study Systemic or oral corticosteroids /&#xD;
             2 weeks Depot corticosteroids /12 weeks Anti-IgE (e.g. Xolair)/ 12 weeks Oral&#xD;
             long-acting beta2-agonists (e.g. bambuterol) and inhaled long-acting beta2-agonists&#xD;
             (e.g. salmeterol, formoterol) or combination products containing inhaled long-acting&#xD;
             beta2-agonists (e.g. Seretide, Symbicort) / 12 hours (the stable dose of ICS/LABA&#xD;
             combination within 2 weeks prior to Visit 1 could be continued during the run-in&#xD;
             period) Theophyllines, slow-release bronchodilators, anticholinergics, ketotifen,&#xD;
             nedocromil sodium, sodium cromoglycate, Anti-leukotrienes including suppressors of&#xD;
             leukotriene production and antagonists / 1 day Inhaled short-acting beta2-agonist / 4&#xD;
             hours (salbutamol will be supplied for rescue during the study) Potent Cytochrome P450&#xD;
             3A4 inhibitors(e.g. ritonavir, ketoconazole, itraconzole) / 4 weeks Prescription or&#xD;
             over the counter medication that would significantly affect the course of asthma, or&#xD;
             interact with sympathomimetic amines, such as: anticonvulsants (barbiturates,&#xD;
             hydantoins, carbamazepine); polycyclic antidepressants; beta-adrenergic blocking&#xD;
             agents; phenothiazines and monoamine oxidase (MAO) inhibitors /1 day Chinese&#xD;
             traditional medicines used for treatment of asthma and other allergic diseases / 1&#xD;
             week Any other investigational drug / 30 days or within 5 half lives, whichever is&#xD;
             longer&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>17 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510180</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Zhanjiang</city>
        <state>Guangdong</state>
        <zip>524001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Xuzhou</city>
        <state>Jiangsu</state>
        <zip>221006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <zip>330006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <zip>110001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <zip>110015</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Yinchuan</city>
        <state>Ningxia</state>
        <zip>750004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <zip>250012</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <zip>250013</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Qingdao</city>
        <state>Shandong</state>
        <zip>266071</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Taiyuan</city>
        <state>Shanxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610072</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Beijing</city>
        <zip>100029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Beijing</city>
        <zip>100088</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chongqing</city>
        <zip>400038</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chongqing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hangzhou</city>
        <zip>310016</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200072</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Wuxi</city>
        <zip>214023</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>https://clinicalstudydatarequest.com</url>
    <description>IPD for this study will be made available via the Clinical Study Data Request site.</description>
  </link>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>August 23, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <results_first_submitted>February 14, 2017</results_first_submitted>
  <results_first_submitted_qc>April 6, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">June 20, 2017</results_first_posted>
  <last_update_submitted>September 11, 2018</last_update_submitted>
  <last_update_submitted_qc>September 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>fluticasone propionate inhalation solution</keyword>
  <keyword>budesonide suspension for inhalation</keyword>
  <keyword>efficacy</keyword>
  <keyword>severe persistent asthma</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <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>Budesonide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD for this study will be made available via the Clinical Study Data Request site.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>IPD is available via the Clinical Study Data Request site (click on the link provided below)</ipd_time_frame>
    <ipd_access_criteria>Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.</ipd_access_criteria>
    <ipd_url>https://clinicalstudydatarequest.com</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 317 Chinese adults and adolescents aged &gt;= 17 years and &lt;= 70 years with severe persistent asthma were planned to be enrolled in study. This study was conducted from 27-September-2012 to 7-November-2013.</recruitment_details>
      <pre_assignment_details>Out of 460 screened participants, 109 were screen failures and 34 were run-in failures. Out of 317 participants, two participants did not receive the study drug and 315 participants received the study drug.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>FP 1 mg BID</title>
          <description>Participants received Fluticasone propionate (FP) oral inhalation (inhal) solution (sol'n) 1 milligram (mg) twice daily (BID) via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
        </group>
        <group group_id="P2">
          <title>BUD 2 mg BID</title>
          <description>Participants received Budesonide (BUD) oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="158"/>
                <participants group_id="P2" count="157"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="123"/>
                <participants group_id="P2" count="130"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>protocol defined stopping criteria</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator discretion</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The analysis was performed on intent-to-treat population. This population comprised of all participants randomized to treatment and who received at least one dose of study medication. Only the participants present at the indicated time point were analyzed.</population>
      <group_list>
        <group group_id="B1">
          <title>FP 1 mg BID</title>
          <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
        </group>
        <group group_id="B2">
          <title>BUD 2 mg BID</title>
          <description>Participants received BUD oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="158"/>
            <count group_id="B2" value="157"/>
            <count group_id="B3" value="315"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51.7" spread="9.84"/>
                    <measurement group_id="B2" value="51.1" spread="6.65"/>
                    <measurement group_id="B3" value="51.4" spread="9.74"/>
                  </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="77"/>
                    <measurement group_id="B2" value="71"/>
                    <measurement group_id="B3" value="148"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="81"/>
                    <measurement group_id="B2" value="86"/>
                    <measurement group_id="B3" value="167"/>
                  </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>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="158"/>
                    <measurement group_id="B2" value="157"/>
                    <measurement group_id="B3" value="315"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline (Day 1 of Treatment Period/Visit 2) in Morning Peak Expiratory Flow (AM PEF) Over 12 Weeks in Intent-to-treat Population</title>
        <description>The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis was performed using analysis of covariance (ANCOVA) model. Abbreviations used in statistical analysis section: standard deviation (SD) and significance (sig)</description>
        <time_frame>Baseline (Visit 2) and up to Week 12</time_frame>
        <population>Intent-to-treat population. Only those participants available at the specified time points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BUD 2 mg BID</title>
            <description>Participants received BUD oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (Day 1 of Treatment Period/Visit 2) in Morning Peak Expiratory Flow (AM PEF) Over 12 Weeks in Intent-to-treat Population</title>
          <description>The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis was performed using analysis of covariance (ANCOVA) model. Abbreviations used in statistical analysis section: standard deviation (SD) and significance (sig)</description>
          <population>Intent-to-treat population. Only those participants available at the specified time points were analyzed.</population>
          <units>Litres/Minute</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="155"/>
                <count group_id="O2" value="152"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.71" spread="3.677"/>
                    <measurement group_id="O2" value="14.51" spread="3.714"/>
                  </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>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the lower limit of the two-sided 95% confidence interval for the treatment difference (FP minus BUD) in the mean change from baseline in daily AM PEF averaged over the 12 week treatment period was greater than -12 L/min.</non_inferiority_desc>
            <p_value>0.733</p_value>
            <p_value_desc>Analysis performed using ANCOVA with covariates of baseline, center, sex, age and treatment</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-1.80</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.19</ci_lower_limit>
            <ci_upper_limit>8.59</ci_upper_limit>
            <estimate_desc>The analysis only included participants who had at least 4 days of non-missing AM PEF data in the baseline week prior to randomization and at least 4 days of non-missing AM PEF data after randomization.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline (Day 1 of Trt Period/Visit 2) in AM PEF Over 12 Weeks in Per Protocol Population</title>
        <description>The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis was performed using analysis of covariance (ANCOVA) model.</description>
        <time_frame>Baseline (Visit 2) and up to Week 12</time_frame>
        <population>Per protocol population. This population comprised of all participants in the intent-to-treat Population who did not have any protocol violations which could impact treatment effect.Only those participants available at the specified time points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BUD 2 mg BID</title>
            <description>Participants received BUD oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (Day 1 of Trt Period/Visit 2) in AM PEF Over 12 Weeks in Per Protocol Population</title>
          <description>The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis was performed using analysis of covariance (ANCOVA) model.</description>
          <population>Per protocol population. This population comprised of all participants in the intent-to-treat Population who did not have any protocol violations which could impact treatment effect.Only those participants available at the specified time points were analyzed.</population>
          <units>Litres/Minute</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="138"/>
                <count group_id="O2" value="142"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.50" spread="3.806"/>
                    <measurement group_id="O2" value="15.78" spread="3.750"/>
                  </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>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority was demonstrated if the lower limit of the two-sided 95% confidence interval for the treatment difference (FP minus BUD) in the mean change from baseline in daily AM PEF averaged over the 12 week treatment period was greater than -12 L/min.</non_inferiority_desc>
            <p_value>0.674</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-2.28</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.95</ci_lower_limit>
            <ci_upper_limit>8.38</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change of Evening PEF From Baseline Over 12 Weeks</title>
        <description>The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the evening PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily PM PEF averaged over the 12-weeks treatment period.</description>
        <time_frame>Baseline (Visit 2) and up to Week 12</time_frame>
        <population>Intent-to-treat population. Only those participants available at the indicated time points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BUD 2 mg BID</title>
            <description>Participants received BUD oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change of Evening PEF From Baseline Over 12 Weeks</title>
          <description>The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the evening PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily PM PEF averaged over the 12-weeks treatment period.</description>
          <population>Intent-to-treat population. Only those participants available at the indicated time points were analyzed.</population>
          <units>Litres/Minute</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="156"/>
                <count group_id="O2" value="153"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.39" spread="3.469"/>
                    <measurement group_id="O2" value="15.16" spread="3.504"/>
                  </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>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.579</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-2.77</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.57</ci_lower_limit>
            <ci_upper_limit>7.04</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Percentage of Symptom-free 24-hour Periods From Baseline Over 12 Weeks</title>
        <description>While calculating symptom-free 24-hour periods, a given 24-hour period was set to be &quot;symptom free&quot; only if the participant's responses to both the morning and evening assessments indicated no symptoms. The Baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. Change from Baseline was calculated as the difference between the value of the endpoint at the time point of interest and the baseline value. The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.</description>
        <time_frame>Baseline (Visit 2) and over 12 Weeks</time_frame>
        <population>Intent-to-treat population. Only those participants available at the indicated time points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BUD 2 mg BID</title>
            <description>Participants received BUD oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Percentage of Symptom-free 24-hour Periods From Baseline Over 12 Weeks</title>
          <description>While calculating symptom-free 24-hour periods, a given 24-hour period was set to be &quot;symptom free&quot; only if the participant's responses to both the morning and evening assessments indicated no symptoms. The Baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. Change from Baseline was calculated as the difference between the value of the endpoint at the time point of interest and the baseline value. The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.</description>
          <population>Intent-to-treat population. Only those participants available at the indicated time points were analyzed.</population>
          <units>Percentage of symptom-free 24-hour</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="156"/>
                <count group_id="O2" value="153"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.77" spread="2.340"/>
                    <measurement group_id="O2" value="21.15" spread="2.364"/>
                  </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>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.854</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.62</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.00</ci_lower_limit>
            <ci_upper_limit>7.24</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Day-time and Night-time Symptom Scores Per Participant Over 12 Weeks</title>
        <description>Participants recorded day-time symptom score every day in the morning and evening at bedtime before taking any rescue or study medication and before PEF measurement, using 6 point scale on Diary Card indicating 0 = No symptoms during the day and 5 =Symptoms so severe that participant could not go to work or perform normal daily activities. Night time symptoms were scored while waking in the morning on a scale of 0 (no symptoms) to 4 (severe). The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.</description>
        <time_frame>Over 12 Weeks</time_frame>
        <population>Intent-to-treat population. Only those participants available at the indicated time points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BUD 2 mg BID</title>
            <description>Participants received BUD oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Day-time and Night-time Symptom Scores Per Participant Over 12 Weeks</title>
          <description>Participants recorded day-time symptom score every day in the morning and evening at bedtime before taking any rescue or study medication and before PEF measurement, using 6 point scale on Diary Card indicating 0 = No symptoms during the day and 5 =Symptoms so severe that participant could not go to work or perform normal daily activities. Night time symptoms were scored while waking in the morning on a scale of 0 (no symptoms) to 4 (severe). The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.</description>
          <population>Intent-to-treat population. Only those participants available at the indicated time points were analyzed.</population>
          <units>Score on Scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="156"/>
                <count group_id="O2" value="153"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Median day-time symptom score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0" upper_limit="4"/>
                    <measurement group_id="O2" value="1.0" lower_limit="0" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Median night-time symptom score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0" upper_limit="2"/>
                    <measurement group_id="O2" value="1.0" lower_limit="0" upper_limit="3"/>
                  </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>This statistical analysis is for comparison of FP 1 mg BID and BUD 2 mg BID in median day-time symptom score</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.123</p_value>
            <method>Wilcoxon rank sum test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This statistical analysis is for comparison of FP 1 mg BID and BUD 2 mg BID in median night-time symptom score</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.949</p_value>
            <method>Wilcoxon rank sum test.</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Percentage of Rescue-free 24-hour Periods From Baseline Over 12 Weeks</title>
        <description>While calculating rescue-free 24-hour periods, the 24-hour period was only set to be &quot;rescue free&quot; if responses to both the morning and evening, assessments indicated no use of rescue medication. If there were symptoms in either the morning or the evening then that 24-hour period was set to as &quot;not symptom free&quot;. Similarly, if there was rescue medication use in either the morning or the evening, then that 24-hour period was set to as &quot;not rescue free&quot;. The Baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.</description>
        <time_frame>Baseline and over 12 weeks</time_frame>
        <population>Intent-to-treat population. Only those participants available at the indicated time points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BUD 2 mg BID</title>
            <description>Participants received BUD oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Percentage of Rescue-free 24-hour Periods From Baseline Over 12 Weeks</title>
          <description>While calculating rescue-free 24-hour periods, the 24-hour period was only set to be &quot;rescue free&quot; if responses to both the morning and evening, assessments indicated no use of rescue medication. If there were symptoms in either the morning or the evening then that 24-hour period was set to as &quot;not symptom free&quot;. Similarly, if there was rescue medication use in either the morning or the evening, then that 24-hour period was set to as &quot;not rescue free&quot;. The Baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.</description>
          <population>Intent-to-treat population. Only those participants available at the indicated time points were analyzed.</population>
          <units>Percentage of rescue -free 24-hours</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="156"/>
                <count group_id="O2" value="154"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.27" spread="2.595"/>
                    <measurement group_id="O2" value="24.01" spread="2.612"/>
                  </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>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.204</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-4.74</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-12.07</ci_lower_limit>
            <ci_upper_limit>2.59</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Number of Times Rescue Medication Use Over 12 Weeks</title>
        <description>Participants recorded the number of inhalations of rescue salbutamol inhalation aerosol used during the day and night. The baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. The analysis only included participants who had at least 2 days of non-missing numbers of times rescue medication (including zero) after randomization.</description>
        <time_frame>Up to week 12</time_frame>
        <population>Intent-to-treat population. Only those participants available at the indicated time points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BUD 2 mg BID</title>
            <description>Participants received BUD oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Number of Times Rescue Medication Use Over 12 Weeks</title>
          <description>Participants recorded the number of inhalations of rescue salbutamol inhalation aerosol used during the day and night. The baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. The analysis only included participants who had at least 2 days of non-missing numbers of times rescue medication (including zero) after randomization.</description>
          <population>Intent-to-treat population. Only those participants available at the indicated time points were analyzed.</population>
          <units>Number of Inhalations</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="156"/>
                <count group_id="O2" value="153"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0" upper_limit="7"/>
                    <measurement group_id="O2" value="0.0" lower_limit="0" upper_limit="4"/>
                  </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>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.170</p_value>
            <method>Wilcoxon Rank sum</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change of Clinical Lung Function Measurement Forced Expiratory Volume in One Second (FEV1) From Baseline Over 12 Weeks</title>
        <description>FEV1 as a measure of lung function assessment was measured at Week 2, 4, 8 and 12. FEV1 measures were performed electronically by spirometry. The highest of three technically acceptable measurements was recorded. FEV1 was measured prior to study drug administration and any rescue salbutamol use. Baseline value was the assessment at Visit 2.Change from baseline was calculated as the value at the specific time point minus baseline value.</description>
        <time_frame>Baseline and at Week 2, 4, 8 and 12</time_frame>
        <population>Intent-to-treat population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>BUD 2 mg BID</title>
            <description>Participants received BUD oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change of Clinical Lung Function Measurement Forced Expiratory Volume in One Second (FEV1) From Baseline Over 12 Weeks</title>
          <description>FEV1 as a measure of lung function assessment was measured at Week 2, 4, 8 and 12. FEV1 measures were performed electronically by spirometry. The highest of three technically acceptable measurements was recorded. FEV1 was measured prior to study drug administration and any rescue salbutamol use. Baseline value was the assessment at Visit 2.Change from baseline was calculated as the value at the specific time point minus baseline value.</description>
          <population>Intent-to-treat population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).</population>
          <units>Litres</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="158"/>
                <count group_id="O2" value="157"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="143"/>
                    <count group_id="O2" value="145"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.122" spread="0.0283"/>
                    <measurement group_id="O2" value="0.161" spread="0.0281"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="128"/>
                    <count group_id="O2" value="134"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.187" spread="0.0333"/>
                    <measurement group_id="O2" value="0.195" spread="0.0328"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="122"/>
                    <count group_id="O2" value="128"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.175" spread="0.0314"/>
                    <measurement group_id="O2" value="0.201" spread="0.0309"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="117"/>
                    <count group_id="O2" value="126"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.217" spread="0.0342"/>
                    <measurement group_id="O2" value="0.200" spread="0.0336"/>
                  </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>This statistical analysis is for comparison of FP 1 mg BID and BUD 2 mg BID in Change of clinical lung function measurement FEV1 at Week 2</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.337</p_value>
            <p_value_desc>Repeated Measures analysis adjusted for baseline, centre, sex, age, visit, treatment, visit by treatment interaction and visit by baseline interaction</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.039</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.118</ci_lower_limit>
            <ci_upper_limit>0.041</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This statistical analysis is for comparison of FP 1 mg BID and BUD 2 mg BID in Change of clinical lung function measurement FEV1 at Week 4</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.866</p_value>
            <p_value_desc>Repeated Measures analysis adjusted for baseline, center, sex, age, visit, treatment, visit by treatment interaction and visit by baseline interaction.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.008</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.101</ci_lower_limit>
            <ci_upper_limit>0.085</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This statistical analysis is for comparison of FP 1 mg BID and BUD 2 mg BID in Change of clinical lung function measurement FEV1 at Week 8</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.566</p_value>
            <p_value_desc>Repeated Measures analysis adjusted for baseline, center, sex, age, visit, treatment, visit by treatment interaction and visit by baseline interaction</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.025</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.113</ci_lower_limit>
            <ci_upper_limit>0.062</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>This statistical analysis is for comparison of FP 1 mg BID and BUD 2 mg BID in Change of clinical lung function measurement FEV1 at Week 12</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.727</p_value>
            <p_value_desc>Repeated Measures analysis adjusted for baseline, center, sex, age, visit, treatment, visit by treatment interaction and visit by baseline interaction.</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.017</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.078</ci_lower_limit>
            <ci_upper_limit>0.112</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution- Time to Maximum Observed Plasma Concentration (Tmax)</title>
        <description>Tmax is defined as the time to maximum observed plasma concentration. Blood Pharmacokinetic (PK) samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of the last dose.</description>
        <time_frame>Pre-dose, 0.5 hour (h), 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2</time_frame>
        <population>Pharmacokinetics population included all participants whose PK samples were obtained and analyzed. Only those participants available at the indicated time points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution- Time to Maximum Observed Plasma Concentration (Tmax)</title>
          <description>Tmax is defined as the time to maximum observed plasma concentration. Blood Pharmacokinetic (PK) samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of the last dose.</description>
          <population>Pharmacokinetics population included all participants whose PK samples were obtained and analyzed. Only those participants available at the indicated time points were analyzed.</population>
          <units>Hour</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.905" spread="59.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-maximum Observed Plasma Concentration (Cmax)</title>
        <description>Cmax was defined as maximum observed plasma concentration. Blood PK samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of last dose.</description>
        <time_frame>Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2</time_frame>
        <population>Pharmacokinetic population. Only those participants available at the indicated time points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-maximum Observed Plasma Concentration (Cmax)</title>
          <description>Cmax was defined as maximum observed plasma concentration. Blood PK samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of last dose.</description>
          <population>Pharmacokinetic population. Only those participants available at the indicated time points were analyzed.</population>
          <units>picogram per milliliter (pg/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.24" spread="115.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-area Under the Plasma Concentration-time Curve for the Dose Interval [AUC (0-τ)]</title>
        <description>AUC (0-τ) was defined as the area under the plasma concentration-time curve for the dose interval. Blood PK samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of last dose.</description>
        <time_frame>Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2</time_frame>
        <population>Pharmacokinetic population. Only those participants available at the indicated time points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>FP 1 mg BID</title>
            <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-area Under the Plasma Concentration-time Curve for the Dose Interval [AUC (0-τ)]</title>
          <description>AUC (0-τ) was defined as the area under the plasma concentration-time curve for the dose interval. Blood PK samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of last dose.</description>
          <population>Pharmacokinetic population. Only those participants available at the indicated time points were analyzed.</population>
          <units>Picogram hours per milliliter (pg*h/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="403.0958" spread="70.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to Week 12</time_frame>
      <desc>Intent-to-treat population was used to assess adverse events up to Week 12.</desc>
      <group_list>
        <group group_id="E1">
          <title>FP 1 mg BID</title>
          <description>Participants received FP oral inhalation solution 1 mg BID via nebulizer for a treatment period of 12 weeks. participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
        </group>
        <group group_id="E2">
          <title>BUD 2 mg BID</title>
          <description>Participants received BUD oral suspension for inhalation 2 mg BID via nebulizer for a treatment period of 12 weeks participants were allowed to use salbutamol aerosol inhaler for rescue of symptoms, and were followed-up for 2 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Spondylolisthesis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrotic syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>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="23" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="158"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="157"/>
              </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>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</phone>
    </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/NCT01687283
org study id: 114219
nct id: NCT01687283
lead sponsor: 
has dmc: No
This is a multicentre, randomized, single-blind, active-controlled, parallel-group phase III
      local registration study for a treatment period of 12 weeks. This study aims to assess the
      effectiveness and safety of fluticasone propionate 1mg via nebulizer BID in treatment of
      Chinese adult and adolescent patients with severe persistent asthma for a treatment period of
      12 weeks versus budesonide 2mg via nebulizer BID. The steady-state plasma pharmacokinetics of
      fluticasone propionate inhalation solution will also be assessed.
Male or female subjects between 17 to 70 (inclusive) years of age with severe persistent
      asthma meeting the inclusion criteria and having completed the screening period of 2 weeks
      will, in a proportion of 1:1, randomly receive fluticasone propionate 1mg via nebulizer BID
      or budesonide 2mg via nebulizer BID for a treatment period of 12 weeks. The clinic visit will
      be arranged at 2 weeks, 4 weeks, 8 weeks and 12 weeks during study treatment. If the subjects
      meet the criteria of pre-defined asthma control at treatment 4 weeks or 8 weeks, they will
      have one chance to be treated with the half dose of study drug. 2 weeks after completion of
      study treatment or after early withdrawal from study, the follow-up visit will be performed
      to assess the post-treatment adverse events. The primary endpoint is the mean change from
      baseline in morning peak expiratory flow (PEF) over the 12 week treatment period. Safety
      assessments include adverse events, vital signs, oral and oropharyngeal candidiasis,
      hematological, biochemical tests), 24-hour urinary cortisol and 12-lead ECG. The steady-state
      plasma pharmacokinetics of fluticasone propionate inhalation solution will also be assessed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Change From Baseline (Day 1 of Treatment Period/Visit 2) in Morning Peak Expiratory Flow (AM PEF) Over 12 Weeks in Intent-to-treat Population
time frame: Baseline (Visit 2) and up to Week 12
description: The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis was performed using analysis of covariance (ANCOVA) model. Abbreviations used in statistical analysis section: standard deviation (SD) and significance (sig)
measure: Change From Baseline (Day 1 of Trt Period/Visit 2) in AM PEF Over 12 Weeks in Per Protocol Population
time frame: Baseline (Visit 2) and up to Week 12
description: The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis was performed using analysis of covariance (ANCOVA) model.
measure: Mean Change of Evening PEF From Baseline Over 12 Weeks
time frame: Baseline (Visit 2) and up to Week 12
description: The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the evening PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily PM PEF averaged over the 12-weeks treatment period.
measure: Mean Change in Percentage of Symptom-free 24-hour Periods From Baseline Over 12 Weeks
time frame: Baseline (Visit 2) and over 12 Weeks
description: While calculating symptom-free 24-hour periods, a given 24-hour period was set to be "symptom free" only if the participant's responses to both the morning and evening assessments indicated no symptoms. The Baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. Change from Baseline was calculated as the difference between the value of the endpoint at the time point of interest and the baseline value. The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.
measure: Median Day-time and Night-time Symptom Scores Per Participant Over 12 Weeks
time frame: Over 12 Weeks
description: Participants recorded day-time symptom score every day in the morning and evening at bedtime before taking any rescue or study medication and before PEF measurement, using 6 point scale on Diary Card indicating 0 = No symptoms during the day and 5 =Symptoms so severe that participant could not go to work or perform normal daily activities. Night time symptoms were scored while waking in the morning on a scale of 0 (no symptoms) to 4 (severe). The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.
measure: Mean Change in Percentage of Rescue-free 24-hour Periods From Baseline Over 12 Weeks
time frame: Baseline and over 12 weeks
description: While calculating rescue-free 24-hour periods, the 24-hour period was only set to be "rescue free" if responses to both the morning and evening, assessments indicated no use of rescue medication. If there were symptoms in either the morning or the evening then that 24-hour period was set to as "not symptom free". Similarly, if there was rescue medication use in either the morning or the evening, then that 24-hour period was set to as "not rescue free". The Baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. The value provided in outcome measure data is a consolidated value over Weeks 1 to 12.
measure: Median Number of Times Rescue Medication Use Over 12 Weeks
time frame: Up to week 12
description: Participants recorded the number of inhalations of rescue salbutamol inhalation aerosol used during the day and night. The baseline value was Visit 2 assessment and was derived from the last 7 days of the daily diary prior to the randomization. The analysis only included participants who had at least 2 days of non-missing numbers of times rescue medication (including zero) after randomization.
measure: Change of Clinical Lung Function Measurement Forced Expiratory Volume in One Second (FEV1) From Baseline Over 12 Weeks
time frame: Baseline and at Week 2, 4, 8 and 12
description: FEV1 as a measure of lung function assessment was measured at Week 2, 4, 8 and 12. FEV1 measures were performed electronically by spirometry. The highest of three technically acceptable measurements was recorded. FEV1 was measured prior to study drug administration and any rescue salbutamol use. Baseline value was the assessment at Visit 2.Change from baseline was calculated as the value at the specific time point minus baseline value.
measure: Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution- Time to Maximum Observed Plasma Concentration (Tmax)
time frame: Pre-dose, 0.5 hour (h), 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2
description: Tmax is defined as the time to maximum observed plasma concentration. Blood Pharmacokinetic (PK) samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of the last dose.
measure: Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-maximum Observed Plasma Concentration (Cmax)
time frame: Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2
description: Cmax was defined as maximum observed plasma concentration. Blood PK samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of last dose.
measure: Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-area Under the Plasma Concentration-time Curve for the Dose Interval [AUC (0-τ)]
time frame: Pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose at Week 2
description: AUC (0-τ) was defined as the area under the plasma concentration-time curve for the dose interval. Blood PK samples were taken on Visit 3 (Day 14±2) pre-dose, 0.5h, 1h, 2h, 3h, 4h, 6h, 8h and 12h post dose from participants. Blood sample for PK analysis, obtained within 72 hours of last dose.
arm group label: fluticasone propionate
arm group type: Experimental
description: 1 mg BID inhalation via nebulizer
arm group label: budesonide suspension
arm group type: Active Comparator
description: 2 mg BID inhalation via nebulizer
intervention type: Drug
intervention name: fluticasone propionate inhalation solution
description: 1 mg BID inhalation for 12 weeks with one possible chance to change to 0.5 mg BID
arm group label: fluticasone propionate
intervention type: Drug
intervention name: budesonide suspension
description: 2 mg BID inhalation for 12 weeks with one possible chance to change to 1 mg BID
arm group label: budesonide suspension
criteria: 
gender: All
minimum age: 17 Years
maximum age: 70 Years
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
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country: China
url: https://clinicalstudydatarequest.com
description: IPD for this study will be made available via the Clinical Study Data Request site.
responsible party type: Sponsor
mesh term: Asthma
mesh term: Fluticasone
mesh term: Xhance
mesh term: Budesonide
sharing ipd: Yes
ipd description: IPD for this study will be made available via the Clinical Study Data Request site.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
ipd access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
ipd url: https://clinicalstudydatarequest.com
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 