<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/NCT02224157</url>
  </required_header>
  <id_info>
    <org_study_id>D589SC00003</org_study_id>
    <secondary_id>2013-004473-28</secondary_id>
    <nct_id>NCT02224157</nct_id>
  </id_info>
  <brief_title>A Clinical Study to Evaluate Symbicort Turbuhaler Used 'as Needed' in Adults and Adolescents With Asthma</brief_title>
  <acronym>SYGMA2</acronym>
  <official_title>A Clinical Study Comparing Symbicort 'as Needed' With Pulmicort Twice Daily Plus Terbutaline 'as Needed' in Adult and Adolescent Patients With Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test if Symbicort (budesonide/formoterol) Turbuhaler is&#xD;
      effective in treating asthma when used 'as needed' in patients with milder asthma. The&#xD;
      efficacy of Symbicort 'as needed' will be compared with Pulmicort (budesonide) Turbuhaler&#xD;
      twice daily plus terbutaline Turbuhaler 'as needed'&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A 52-week, double-blind, randomised, multi-centre, phase III, parallel-group study in&#xD;
      patients 12 years and older with asthma, evaluating the efficacy and safety of Symbicort&#xD;
      (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' compared with Pulmicort&#xD;
      (budesonide) Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg 'as needed'&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 28, 2014</start_date>
  <completion_date type="Actual">August 16, 2017</completion_date>
  <primary_completion_date type="Actual">August 16, 2017</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis</measure>
    <time_frame>up to 52 weeks</time_frame>
    <description>Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Annual Severe Asthma Exacerbation Rate - Superiority Analysis</measure>
    <time_frame>up to 52 weeks</time_frame>
    <description>Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Experiencing at Least One Severe Asthma Exacerbation</measure>
    <time_frame>Day 1 up to 52 weeks</time_frame>
    <description>A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Change From Baseline in Pre-bronchodilator FEV1</measure>
    <time_frame>Study weeks 0,17, 34, 52</time_frame>
    <description>The average change from baseline (baseline defined by measurement at week 0, prior to first dose of IP) to the treatment period average assessed over the entire treatment period in pre-bronchodilator FEV1 was derived by computing a contrast for the mean across the post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Study Specific Asthma Related Discontinuation</measure>
    <time_frame>Day 1 up to 52 weeks</time_frame>
    <description>The following two criteria lead to discontinuation from the IP due to asthma related events: A severe asthma exacerbation with duration for more than 3 weeks, and/or three severe asthma exacerbations during 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Change From Baseline in 'as Needed' Use</measure>
    <time_frame>Week 0 up to 52 weeks</time_frame>
    <description>'As-needed' use change from baseline over the randomised treatment period. Baseline was defined as the last 10 days of the run-in period. 'As needed' use was calculated as the cumulative doses of 'as-needed' medication over the randomised treatment period divided by the follow-up time (number of days - 1). ie, average number of inhalations per day.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Percent of 'as Needed' Free Days</measure>
    <time_frame>Week 0 up to 52 weeks</time_frame>
    <description>'As needed' free days (%) change from baseline during randomised treatment period. An 'as-needed' free day was defined as a day and night with no use of 'as needed' medication. Variable analysed is the percentage (%) of 'as-needed' free days during the randomised treatment period. Baseline is defined by the last 10 days of the run-in period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Controller Use Days</measure>
    <time_frame>Week 0 up to 52 weeks</time_frame>
    <description>ICS controller use days (%) during the randomised treatment period is calculated as the cumulative days when any controller medication (containing ICS) was taken including maintenance (Pulmicort bid group) and 'as needed' medication (Symbicort 'as needed' group) and additional prescribed ICS for asthma (all treatment groups), divided by the number of days in the randomised treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Change From Baseline in Asthma Control Questionnaire (5-item Version) - ACQ-5 Score</measure>
    <time_frame>Study weeks 0, 17, 34, 52</time_frame>
    <description>ACQ questionnaire contains five questions on patients' symptoms, which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor control). The score is the mean score of all questions for which responses are provided. The average change from baseline to treatment period average in ACQ-5 was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Change From Baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) Score</measure>
    <time_frame>Study weeks 0,17, 34, 52</time_frame>
    <description>AQLQ(S) consists of 32 questions in 4 domains. Each question is assessed on a 7-point scale from 1 to 7, with higher values indicating better health-related quality of life. The overall score is calculated as the mean score of all 32 items. The average change from baseline to treatment period average in AQLQ(S) overall score was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4215</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Symbicort &quot;as needed&quot;+placebo Pulmicort bid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' + Placebo Pulmicort Turbuhaler 200 μg bid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pulmicort bid + terbutaline &quot;as needed&quot;</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg Turbuhaler 'as needed'</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>budesonide/formoterol 'as needed' + budesonide placebo bid</intervention_name>
    <description>Symbicort (budesonide/ formoterol) 160/4.5 μg powder for inhalation 'as needed' plus Pulmicort placebo 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening), 52-week treatment</description>
    <arm_group_label>Symbicort &quot;as needed&quot;+placebo Pulmicort bid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>budesonode bid + terbutaline 'as needed'</intervention_name>
    <description>Pulmicort (budesonide) 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening) plus terbutaline 0.4 mg powder for inhalation 'as needed', 52-week treatment</description>
    <arm_group_label>Pulmicort bid + terbutaline &quot;as needed&quot;</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of informed consent prior to any study specific procedures. For patients&#xD;
             under-age, signed informed consent from both the patient and the patient's&#xD;
             parent/legal guardian is required&#xD;
&#xD;
          2. Male or Female, ≥12 years of age&#xD;
&#xD;
          3. Documented diagnosis of asthma for at least 6 months prior to Visit 1&#xD;
&#xD;
          4. Patients who are in need of GINA step 2 treatment&#xD;
&#xD;
          5. Patients treated with a short acting inhaled bronchodilator(s) only should have&#xD;
             pre-bronchodilator FEV1 ≥ 60 % of predicted normal (PN) and post-bronchodilator FEV1 ≥&#xD;
             80 % PN&#xD;
&#xD;
          6. Patients treated with low stable dose of ICS or leukotriene antagonists in addition to&#xD;
             short acting inhaled bronchodilator(s) should have pre-bronchodilator FEV1 ≥80 % PN&#xD;
&#xD;
          7. Patients should have reversible airway obstruction&#xD;
&#xD;
          8. To be randomized patients must have used Bricanyl Turbuhaler as needed on at least 3&#xD;
             separate days during the last week of the run in period&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient has a history of life-threatening asthma including intubation and intensive&#xD;
             care unit admission&#xD;
&#xD;
          2. Patient has had an asthma worsening requiring change in treatment other than short&#xD;
             acting inhaled bronchodilator(s) within 30 days prior to Visit 1 and from Visit 1&#xD;
             until randomization&#xD;
&#xD;
          3. Patient has required treatment with oral, rectal or parenteral GCS within 30 days&#xD;
             and/or depot parenteral GCS within 12 weeks prior to Visit 1&#xD;
&#xD;
          4. Current or previous smoker with a smoking history of ≥ 10 pack years&#xD;
&#xD;
          5. Pregnancy, breast-feeding or planned pregnancy during the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carin Jorup, MD</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca Research &amp; Development</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sydney</city>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Botucatu</city>
        <zip>18618-970</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Florianopolis</city>
        <zip>88040-970</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Goiania</city>
        <zip>74110 030</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto Alegre</city>
        <zip>9002-060</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90020-060</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90110-270</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90610-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto Alegre</city>
        <zip>91350-200</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Salvador</city>
        <zip>41940-455</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santo Andre</city>
        <zip>09080-110</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sao Paulo</city>
        <zip>04020-060</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sao Paulo</city>
        <zip>04101-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sao Paulo</city>
        <zip>04266-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sorocaba</city>
        <zip>18040-425</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>São Paulo</city>
        <zip>02189-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>São Paulo</city>
        <zip>05403-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Blagoevgrad</city>
        <zip>2700</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pernik</city>
        <zip>2300</zip>
        <country>Bulgaria</country>
      </address>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Petrich</city>
        <zip>2850</zip>
        <country>Bulgaria</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pleven</city>
        <zip>5800</zip>
        <country>Bulgaria</country>
      </address>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Razlog</city>
        <zip>2760</zip>
        <country>Bulgaria</country>
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  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sliven</city>
        <zip>8800</zip>
        <country>Bulgaria</country>
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    </facility>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Smolyan</city>
        <zip>4700</zip>
        <country>Bulgaria</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1404</zip>
        <country>Bulgaria</country>
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    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1407</zip>
        <country>Bulgaria</country>
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    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1408</zip>
        <country>Bulgaria</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1612</zip>
        <country>Bulgaria</country>
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    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1618</zip>
        <country>Bulgaria</country>
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    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
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  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Stara Zagora</city>
        <zip>6000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Varna</city>
        <zip>9000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Veliko Tarnovo</city>
        <zip>5000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Vidin</city>
        <zip>3700</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yambol</city>
        <zip>8600</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Curico</city>
        <zip>3341643</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Quillota</city>
        <zip>2260000</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santiago</city>
        <zip>404366</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santiago</city>
        <zip>8207257</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santiago</city>
        <zip>8320000</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Talca</city>
        <zip>3465584</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Viña del Mar</city>
        <zip>2520000</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barranquilla</city>
        <zip>80001</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bogota</city>
        <zip>111511</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bogotá</city>
        <zip>110221</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bogotá</city>
        <zip>111211</zip>
        <country>Colombia</country>
      </address>
    </facility>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Medellin</city>
        <zip>5001000</zip>
        <country>Colombia</country>
      </address>
    </facility>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ceska Lipa</city>
        <zip>470 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kladno</city>
        <zip>272 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kralupy nad Vltavou</city>
        <zip>278 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kutna Hora</city>
        <zip>284 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Liberec 1</city>
        <zip>460 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Neratovice</city>
        <zip>277 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
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  </link>
  <link>
    <url>http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&amp;studyid=2649&amp;filename=D589SC00003-statistical-analysis-plan-edition-2_06SEP2017_pdfa.pdf</url>
    <description>D589SC00003-statistical-analysis-plan-edition-2_06SEP2017_pdfa</description>
  </link>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <results_first_submitted>August 16, 2018</results_first_submitted>
  <results_first_submitted_qc>November 6, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 25, 2019</results_first_posted>
  <last_update_submitted>November 6, 2019</last_update_submitted>
  <last_update_submitted_qc>November 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Budesonide</mesh_term>
    <mesh_term>Terbutaline</mesh_term>
    <mesh_term>Formoterol Fumarate</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 6, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT02224157/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 12, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT02224157/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>4215 patients were enrolled. 26 patients were randomised in error and hence never recieved treatment.</recruitment_details>
      <pre_assignment_details>Screening Details Eligibility was assessed at Visits 1, 2 and 3. IC was obtained at V1. At V2, patients stopped pre-study asthma medications and entered a 2 to 4 week run-in period on SABA as needed only (Bricanyl Turbuhaler 0.5 mg). Lung function was assessed by spirometry to confirm eligibility. Eligible patients were randomised at V3.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
          <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
        </group>
        <group group_id="P2">
          <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
          <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2095"/>
                <participants group_id="P2" count="2094"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Patients Who Completed Treatment</title>
              <participants_list>
                <participants group_id="P1" count="1924"/>
                <participants group_id="P2" count="1903"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1985"/>
                <participants group_id="P2" count="1983"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="110"/>
                <participants group_id="P2" count="111"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Severe non-compliance to protocol</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject decision</title>
              <participants_list>
                <participants group_id="P1" count="58"/>
                <participants group_id="P2" count="50"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Prematurely closed site</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Eligibility criteria not fulfilled</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full analysis set</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
          <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
        </group>
        <group group_id="B2">
          <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
          <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</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="2089"/>
            <count group_id="B2" value="2087"/>
            <count group_id="B3" value="4176"/>
          </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="41.3" spread="16.8"/>
                    <measurement group_id="B2" value="40.7" spread="17.1"/>
                    <measurement group_id="B3" value="41.0" spread="17.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</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="1308"/>
                    <measurement group_id="B2" value="1289"/>
                    <measurement group_id="B3" value="2597"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="781"/>
                    <measurement group_id="B2" value="798"/>
                    <measurement group_id="B3" value="1579"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <population>Full Analysis Set</population>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="399"/>
                    <measurement group_id="B2" value="403"/>
                    <measurement group_id="B3" value="802"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1408"/>
                    <measurement group_id="B2" value="1406"/>
                    <measurement group_id="B3" value="2814"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="211"/>
                    <measurement group_id="B2" value="211"/>
                    <measurement group_id="B3" value="422"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis</title>
        <description>Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation</description>
        <time_frame>up to 52 weeks</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
            <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
          </group>
          <group group_id="O2">
            <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
            <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis</title>
          <description>Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation</description>
          <population>Full analysis set</population>
          <units>exacerbations per participant year</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2089"/>
                <count group_id="O2" value="2087"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.11" lower_limit="0.10" upper_limit="0.13"/>
                    <measurement group_id="O2" value="0.12" lower_limit="0.10" upper_limit="0.14"/>
                  </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</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority analysis based on CI instead of p-value, hence no p-value calculated for this analysis. Upper limit of the 1-sided 95% confidence limit &lt;1.2 indicates Symbicort 'as needed' is non-inferior to Pulmicort bid</non_inferiority_desc>
            <param_type>Rate ratio</param_type>
            <param_value>0.97</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>1-Sided</ci_n_sides>
            <ci_upper_limit>1.16</ci_upper_limit>
            <estimate_desc>A rate ratio less than 1 indicates a lower rate of exacerbations in the Symbicort 'as needed' treatment group.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Experiencing at Least One Severe Asthma Exacerbation</title>
        <description>A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids.</description>
        <time_frame>Day 1 up to 52 weeks</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
            <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
          </group>
          <group group_id="O2">
            <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
            <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing at Least One Severe Asthma Exacerbation</title>
          <description>A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids.</description>
          <population>Full analysis set</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2089"/>
                <count group_id="O2" value="2087"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="177"/>
                    <measurement group_id="O2" value="184"/>
                  </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</non_inferiority_type>
            <p_value>0.664</p_value>
            <method>Regression, Cox</method>
            <method_desc>Cox regression model with randomised treatment, pre-study treatment and region as covariates.</method_desc>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.955</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.777</ci_lower_limit>
            <ci_upper_limit>1.174</ci_upper_limit>
            <estimate_desc>A hazard ratio less than 1 indicates that Symbicort 'as needed' prolongs the time to first severe exacerbation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Change From Baseline in Pre-bronchodilator FEV1</title>
        <description>The average change from baseline (baseline defined by measurement at week 0, prior to first dose of IP) to the treatment period average assessed over the entire treatment period in pre-bronchodilator FEV1 was derived by computing a contrast for the mean across the post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.</description>
        <time_frame>Study weeks 0,17, 34, 52</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
            <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
          </group>
          <group group_id="O2">
            <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
            <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
          </group>
        </group_list>
        <measure>
          <title>Average Change From Baseline in Pre-bronchodilator FEV1</title>
          <description>The average change from baseline (baseline defined by measurement at week 0, prior to first dose of IP) to the treatment period average assessed over the entire treatment period in pre-bronchodilator FEV1 was derived by computing a contrast for the mean across the post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.</description>
          <population>Full analysis set</population>
          <units>mL</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2089"/>
                <count group_id="O2" value="2087"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104.0" lower_limit="88.5" upper_limit="119.6"/>
                    <measurement group_id="O2" value="136.6" lower_limit="121.1" upper_limit="152.2"/>
                  </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</non_inferiority_type>
            <p_value>0.003</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Rand treatment,pre-study treatment,region,visit,rand treatment by visit; fixed effects. Patient; random effect, baseline FEV1; covariate.</method_desc>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-32.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-53.7</ci_lower_limit>
            <ci_upper_limit>-11.4</ci_upper_limit>
            <estimate_desc>Mean difference greater than 0 favours Symbicort 'as needed'. Estimate corresponds to average treatment effect across all treatment visits.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Study Specific Asthma Related Discontinuation</title>
        <description>The following two criteria lead to discontinuation from the IP due to asthma related events: A severe asthma exacerbation with duration for more than 3 weeks, and/or three severe asthma exacerbations during 6 months.</description>
        <time_frame>Day 1 up to 52 weeks</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
            <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
          </group>
          <group group_id="O2">
            <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
            <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Study Specific Asthma Related Discontinuation</title>
          <description>The following two criteria lead to discontinuation from the IP due to asthma related events: A severe asthma exacerbation with duration for more than 3 weeks, and/or three severe asthma exacerbations during 6 months.</description>
          <population>Full analysis set</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2089"/>
                <count group_id="O2" value="2087"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Change From Baseline in 'as Needed' Use</title>
        <description>'As-needed' use change from baseline over the randomised treatment period. Baseline was defined as the last 10 days of the run-in period. 'As needed' use was calculated as the cumulative doses of 'as-needed' medication over the randomised treatment period divided by the follow-up time (number of days - 1). ie, average number of inhalations per day.</description>
        <time_frame>Week 0 up to 52 weeks</time_frame>
        <population>Full analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
            <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
          </group>
          <group group_id="O2">
            <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
            <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
          </group>
        </group_list>
        <measure>
          <title>Average Change From Baseline in 'as Needed' Use</title>
          <description>'As-needed' use change from baseline over the randomised treatment period. Baseline was defined as the last 10 days of the run-in period. 'As needed' use was calculated as the cumulative doses of 'as-needed' medication over the randomised treatment period divided by the follow-up time (number of days - 1). ie, average number of inhalations per day.</description>
          <population>Full analysis set.</population>
          <units>Number of inhalations per day</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2089"/>
                <count group_id="O2" value="2087"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.84" lower_limit="-0.86" upper_limit="-0.81"/>
                    <measurement group_id="O2" value="-0.87" lower_limit="-0.89" upper_limit="-0.84"/>
                  </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</non_inferiority_type>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>0.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.00</ci_lower_limit>
            <ci_upper_limit>0.07</ci_upper_limit>
            <estimate_desc>A mean difference less than zero indicates a larger mean reduction in number of 'as needed' inhalations in the Symbicort 'as needed' group.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Percent of 'as Needed' Free Days</title>
        <description>'As needed' free days (%) change from baseline during randomised treatment period. An 'as-needed' free day was defined as a day and night with no use of 'as needed' medication. Variable analysed is the percentage (%) of 'as-needed' free days during the randomised treatment period. Baseline is defined by the last 10 days of the run-in period.</description>
        <time_frame>Week 0 up to 52 weeks</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
            <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
          </group>
          <group group_id="O2">
            <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
            <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Percent of 'as Needed' Free Days</title>
          <description>'As needed' free days (%) change from baseline during randomised treatment period. An 'as-needed' free day was defined as a day and night with no use of 'as needed' medication. Variable analysed is the percentage (%) of 'as-needed' free days during the randomised treatment period. Baseline is defined by the last 10 days of the run-in period.</description>
          <population>Full analysis set</population>
          <units>Percentage of 'as needed' free days</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2089"/>
                <count group_id="O2" value="2087"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.01" lower_limit="39.90" upper_limit="42.12"/>
                    <measurement group_id="O2" value="47.86" lower_limit="46.75" upper_limit="48.98"/>
                  </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</non_inferiority_type>
            <p_value>&lt; 0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>adjusted for randomised treatment, pre-study treatment and region as factors and the percent 'as needed' free days during run-in as a cont covariate.</method_desc>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-6.85</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.37</ci_lower_limit>
            <ci_upper_limit>-5.34</ci_upper_limit>
            <estimate_desc>An estimate of difference &gt;0 means that there was a larger increase in the % of 'as needed' free days in the Symbicort 'as-needed' arm.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Controller Use Days</title>
        <description>ICS controller use days (%) during the randomised treatment period is calculated as the cumulative days when any controller medication (containing ICS) was taken including maintenance (Pulmicort bid group) and 'as needed' medication (Symbicort 'as needed' group) and additional prescribed ICS for asthma (all treatment groups), divided by the number of days in the randomised treatment period.</description>
        <time_frame>Week 0 up to 52 weeks</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
            <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
          </group>
          <group group_id="O2">
            <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
            <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Controller Use Days</title>
          <description>ICS controller use days (%) during the randomised treatment period is calculated as the cumulative days when any controller medication (containing ICS) was taken including maintenance (Pulmicort bid group) and 'as needed' medication (Symbicort 'as needed' group) and additional prescribed ICS for asthma (all treatment groups), divided by the number of days in the randomised treatment period.</description>
          <population>Full analysis set</population>
          <units>Percentage of days</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2089"/>
                <count group_id="O2" value="2087"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.45" lower_limit="29.20" upper_limit="31.70"/>
                    <measurement group_id="O2" value="67.92" lower_limit="66.67" upper_limit="69.17"/>
                  </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</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANOVA</method>
            <method_desc>model adjusted for: randomised treatment, pre-study treatment and region.</method_desc>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-37.48</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-39.18</ci_lower_limit>
            <ci_upper_limit>-35.77</ci_upper_limit>
            <estimate_desc>An estimate of difference &gt;0 means that there was a higher % of controller use days in the Symbicort 'as-needed' group.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Change From Baseline in Asthma Control Questionnaire (5-item Version) - ACQ-5 Score</title>
        <description>ACQ questionnaire contains five questions on patients' symptoms, which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor control). The score is the mean score of all questions for which responses are provided. The average change from baseline to treatment period average in ACQ-5 was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.</description>
        <time_frame>Study weeks 0, 17, 34, 52</time_frame>
        <population>Full analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
            <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
          </group>
          <group group_id="O2">
            <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
            <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
          </group>
        </group_list>
        <measure>
          <title>Average Change From Baseline in Asthma Control Questionnaire (5-item Version) - ACQ-5 Score</title>
          <description>ACQ questionnaire contains five questions on patients' symptoms, which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor control). The score is the mean score of all questions for which responses are provided. The average change from baseline to treatment period average in ACQ-5 was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.</description>
          <population>Full analysis set.</population>
          <units>Score</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2089"/>
                <count group_id="O2" value="2087"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.35" lower_limit="-0.38" upper_limit="-0.32"/>
                    <measurement group_id="O2" value="-0.46" lower_limit="-0.49" upper_limit="-0.43"/>
                  </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</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>rand treatment, pre-study treatment, region, visit, rand treat by visit as fixed, patient as random, and baseline ACQ-5 as covariate.</method_desc>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>0.109</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.068</ci_lower_limit>
            <ci_upper_limit>0.150</ci_upper_limit>
            <estimate_desc>Mean difference less than 0 favours Symbicort 'as needed'.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Change From Baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) Score</title>
        <description>AQLQ(S) consists of 32 questions in 4 domains. Each question is assessed on a 7-point scale from 1 to 7, with higher values indicating better health-related quality of life. The overall score is calculated as the mean score of all 32 items. The average change from baseline to treatment period average in AQLQ(S) overall score was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.</description>
        <time_frame>Study weeks 0,17, 34, 52</time_frame>
        <population>Full Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
            <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
          </group>
          <group group_id="O2">
            <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
            <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
          </group>
        </group_list>
        <measure>
          <title>Average Change From Baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) Score</title>
          <description>AQLQ(S) consists of 32 questions in 4 domains. Each question is assessed on a 7-point scale from 1 to 7, with higher values indicating better health-related quality of life. The overall score is calculated as the mean score of all 32 items. The average change from baseline to treatment period average in AQLQ(S) overall score was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.</description>
          <population>Full Analysis Set.</population>
          <units>AQLQ(S) overall score</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2089"/>
                <count group_id="O2" value="2087"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.335" lower_limit="0.305" upper_limit="0.366"/>
                    <measurement group_id="O2" value="0.431" lower_limit="0.400" upper_limit="0.461"/>
                  </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</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>rand treatment, pre-study treatment, region, visit, rand treat by visit as fixed, patient as random and baseline AQLQ as covariate.</method_desc>
            <param_type>Least Square Mean Difference</param_type>
            <param_value>-0.096</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.137</ci_lower_limit>
            <ci_upper_limit>-0.054</ci_upper_limit>
            <estimate_desc>Mean difference greater than 0 favours Symbicort 'as needed'.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Annual Severe Asthma Exacerbation Rate - Superiority Analysis</title>
        <description>Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation</description>
        <time_frame>up to 52 weeks</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
            <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
          </group>
          <group group_id="O2">
            <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
            <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Severe Asthma Exacerbation Rate - Superiority Analysis</title>
          <description>Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation</description>
          <population>Full analysis set</population>
          <units>exacerbations per participant year</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2089"/>
                <count group_id="O2" value="2087"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.11" lower_limit="0.10" upper_limit="0.13"/>
                    <measurement group_id="O2" value="0.12" lower_limit="0.10" upper_limit="0.14"/>
                  </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</non_inferiority_type>
            <p_value>0.754</p_value>
            <method>Negative binomial model</method>
            <method_desc>Adjusted for randomised treatment, pre-study treatment and region. Logarithm of follow-up time is used as an offset variable.</method_desc>
            <param_type>Rate ratio</param_type>
            <param_value>0.97</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.78</ci_lower_limit>
            <ci_upper_limit>1.20</ci_upper_limit>
            <estimate_desc>A rate ratio less than 1 indicates a lower rate of exacerbations in the Symbicort 'as needed' treatment group.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were summarised from Visit 2 throughout the randomised treatment period and including the follow-up period until the last telephone follow-up, or the last contact. Serious adverse events were recorded from the time of informed consent throughout the randomised treatment period and including the folow-up period until last telephone follow-up or last contact.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo Bid + Symbicort 'as Needed' (Experimental)</title>
          <description>Placebo for budesonide (Placebo Turbuhaler) + Symbicort Turbuhaler (budesonide/formoterol 160/4.5 μg)</description>
        </group>
        <group group_id="E2">
          <title>Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator)</title>
          <description>Pulmicort Turbuhaler (budesonide 200 μg) + Terbutaline Turbuhaler 0.4mg 'as needed'</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 20.0</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="2089"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="66" subjects_at_risk="2089"/>
                <counts group_id="E2" subjects_affected="73" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Adams-Stokes syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Atrial fibrilation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Atrioventricular block complete</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Cardiomyopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Degenerative aortic valve disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Deafness neurosensory</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Haemorrhoidal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Incarcerated umbilical hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Biliary colic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Hydrocholecystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Sphincter of Oddi dysfunction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Drug hypersensitivity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Acute sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Chronic sinusitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Dengue fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Pneumonia pneumococcal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Urinary tract infection bacterial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Vestibular neuronitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Abdominal injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Hand fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Humerus fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Ligament injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Lower limb fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Lumbosacral plexus injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Post procedural complication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Post procedural swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Radius fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Wrist fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus inadequate control</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Intervertebral disc protusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Rotator cuff syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Spinal osteoarthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Benign neoplasm of skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Breast cancer female</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Cervix carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Fibroadenoma of breast</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Sebaceous adenoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Seborrhoeic keratosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Uterine leiomyoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carpal tunnel syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Lumbar radiculopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Radiculopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Cystistis interstitial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Ureteric stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Adenomyosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Breast mass</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Endometrial hyperplasia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Endometriosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Menorrhagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Prostatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Rectocele</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Uterine polyp</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="20" subjects_affected="17" subjects_at_risk="2089"/>
                <counts group_id="E2" events="17" subjects_affected="17" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Nasal polyps</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Nasal turbinate hypertrophy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Vocal cord polyp</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Angioedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Hirsutism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Peripheral arterial occlusive disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2089"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Thrombophlebitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2089"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA version 20.0</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="491" subjects_at_risk="2089"/>
                <counts group_id="E2" subjects_affected="519" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="188" subjects_affected="155" subjects_at_risk="2089"/>
                <counts group_id="E2" events="206" subjects_affected="168" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="70" subjects_affected="64" subjects_at_risk="2089"/>
                <counts group_id="E2" events="83" subjects_affected="78" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="90" subjects_affected="81" subjects_at_risk="2089"/>
                <counts group_id="E2" events="112" subjects_affected="89" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="55" subjects_affected="51" subjects_at_risk="2089"/>
                <counts group_id="E2" events="74" subjects_affected="62" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="34" subjects_affected="33" subjects_at_risk="2089"/>
                <counts group_id="E2" events="46" subjects_affected="42" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="69" subjects_affected="51" subjects_at_risk="2089"/>
                <counts group_id="E2" events="68" subjects_affected="50" subjects_at_risk="2087"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="95" subjects_affected="81" subjects_at_risk="2089"/>
                <counts group_id="E2" events="96" subjects_affected="84" subjects_at_risk="2087"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" events="56" subjects_affected="51" subjects_at_risk="2089"/>
                <counts group_id="E2" events="46" subjects_affected="44" subjects_at_risk="2087"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Stefan Ivanov</name_or_title>
      <organization>AstraZeneca AB</organization>
      <phone>000000000</phone>
      <email>information.center@astrazeneca.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02224157
org study id: D589SC00003
secondary id: 2013-004473-28
nct id: NCT02224157
lead sponsor: 
has dmc: No
The purpose of this study is to test if Symbicort (budesonide/formoterol) Turbuhaler is
      effective in treating asthma when used 'as needed' in patients with milder asthma. The
      efficacy of Symbicort 'as needed' will be compared with Pulmicort (budesonide) Turbuhaler
      twice daily plus terbutaline Turbuhaler 'as needed'
A 52-week, double-blind, randomised, multi-centre, phase III, parallel-group study in
      patients 12 years and older with asthma, evaluating the efficacy and safety of Symbicort
      (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' compared with Pulmicort
      (budesonide) Turbuhaler 200 μg twice daily plus terbutaline Turbuhaler 0.4 mg 'as needed'
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Annual Severe Asthma Exacerbation Rate - Non-inferiority Analysis
time frame: up to 52 weeks
description: Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation
measure: Annual Severe Asthma Exacerbation Rate - Superiority Analysis
time frame: up to 52 weeks
description: Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation
measure: Number of Participants Experiencing at Least One Severe Asthma Exacerbation
time frame: Day 1 up to 52 weeks
description: A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids.
measure: Average Change From Baseline in Pre-bronchodilator FEV1
time frame: Study weeks 0,17, 34, 52
description: The average change from baseline (baseline defined by measurement at week 0, prior to first dose of IP) to the treatment period average assessed over the entire treatment period in pre-bronchodilator FEV1 was derived by computing a contrast for the mean across the post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.
measure: Number of Participants With Study Specific Asthma Related Discontinuation
time frame: Day 1 up to 52 weeks
description: The following two criteria lead to discontinuation from the IP due to asthma related events: A severe asthma exacerbation with duration for more than 3 weeks, and/or three severe asthma exacerbations during 6 months.
measure: Average Change From Baseline in 'as Needed' Use
time frame: Week 0 up to 52 weeks
description: 'As-needed' use change from baseline over the randomised treatment period. Baseline was defined as the last 10 days of the run-in period. 'As needed' use was calculated as the cumulative doses of 'as-needed' medication over the randomised treatment period divided by the follow-up time (number of days - 1). ie, average number of inhalations per day.
measure: Change From Baseline in Percent of 'as Needed' Free Days
time frame: Week 0 up to 52 weeks
description: 'As needed' free days (%) change from baseline during randomised treatment period. An 'as-needed' free day was defined as a day and night with no use of 'as needed' medication. Variable analysed is the percentage (%) of 'as-needed' free days during the randomised treatment period. Baseline is defined by the last 10 days of the run-in period.
measure: Percentage of Controller Use Days
time frame: Week 0 up to 52 weeks
description: ICS controller use days (%) during the randomised treatment period is calculated as the cumulative days when any controller medication (containing ICS) was taken including maintenance (Pulmicort bid group) and 'as needed' medication (Symbicort 'as needed' group) and additional prescribed ICS for asthma (all treatment groups), divided by the number of days in the randomised treatment period.
measure: Average Change From Baseline in Asthma Control Questionnaire (5-item Version) - ACQ-5 Score
time frame: Study weeks 0, 17, 34, 52
description: ACQ questionnaire contains five questions on patients' symptoms, which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor control). The score is the mean score of all questions for which responses are provided. The average change from baseline to treatment period average in ACQ-5 was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.
measure: Average Change From Baseline in Asthma Quality of Life Questionnaire Standardised Version - AQLQ(S) Score
time frame: Study weeks 0,17, 34, 52
description: AQLQ(S) consists of 32 questions in 4 domains. Each question is assessed on a 7-point scale from 1 to 7, with higher values indicating better health-related quality of life. The overall score is calculated as the mean score of all 32 items. The average change from baseline to treatment period average in AQLQ(S) overall score was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis.
arm group label: Symbicort "as needed"+placebo Pulmicort bid
arm group type: Experimental
description: Symbicort (budesonide/formoterol) Turbuhaler 160/4.5 μg 'as needed' + Placebo Pulmicort Turbuhaler 200 μg bid
arm group label: Pulmicort bid + terbutaline "as needed"
arm group type: Active Comparator
description: Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg Turbuhaler 'as needed'
intervention type: Drug
intervention name: budesonide/formoterol 'as needed' + budesonide placebo bid
description: Symbicort (budesonide/ formoterol) 160/4.5 μg powder for inhalation 'as needed' plus Pulmicort placebo 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening), 52-week treatment
arm group label: Symbicort "as needed"+placebo Pulmicort bid
intervention type: Drug
intervention name: budesonode bid + terbutaline 'as needed'
description: Pulmicort (budesonide) 200 μg powder for inhalation, 1 inhalation twice daily (morning and evening) plus terbutaline 0.4 mg powder for inhalation 'as needed', 52-week treatment
arm group label: Pulmicort bid + terbutaline "as needed"
criteria: 
gender: All
minimum age: 12 Years
maximum age: 130 Years
healthy volunteers: No
last name: Carin Jorup, MD
role: Study Director
affiliation: AstraZeneca Research & Development
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country: Australia
country: Brazil
country: Bulgaria
country: Chile
country: Colombia
country: Czechia
country: France
country: Germany
country: Hungary
country: Korea, Republic of
country: Mexico
country: New Zealand
country: Peru
country: Philippines
country: Poland
country: Romania
country: Russian Federation
country: Saudi Arabia
country: Slovakia
country: South Africa
country: Spain
country: Sweden
country: Thailand
country: Ukraine
country: Vietnam
country: Argentina
country: Czech Republic
country: Italy
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=2649&filename=d589sc00003-revised-csp-edition-4_12Oct2016_Redacted_pdfa.pdf
description: D589SC00003-revised-csp-edition-4_12Oct2016_Redacted_pdfa
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=2649&filename=D589SC00003-statistical-analysis-plan-edition-2_06SEP2017_pdfa.pdf
description: D589SC00003-statistical-analysis-plan-edition-2_06SEP2017_pdfa
responsible party type: Sponsor
mesh term: Asthma
mesh term: Budesonide
mesh term: Terbutaline
mesh term: Formoterol Fumarate
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 