<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/NCT02238483</url>
  </required_header>
  <id_info>
    <org_study_id>D2550C00005</org_study_id>
    <secondary_id>2014-001053-16</secondary_id>
    <nct_id>NCT02238483</nct_id>
  </id_info>
  <brief_title>A Phase IIa Study to Investigate the Efficacy and Safety of AZD7624 in Chronic Obstructive Pulmonary Disease (COPD) Patients While on Maintenance Therapy</brief_title>
  <official_title>A 12-week Phase IIa, Double-blind, Placebo-controlled, Randomized Study to Investigate the Efficacy and Safety of AZD7624 in COPD Patients With a History of Frequent Acute Exacerbations While on Maintenance Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether AZD7624 can reduce acute Chronic&#xD;
      Obstructive Pulmonary Disease (COPD) exacerbations in patients on COPD maintenance therapy&#xD;
      with a history of frequent acute exacerbations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 28, 2014</start_date>
  <completion_date type="Actual">April 4, 2016</completion_date>
  <primary_completion_date type="Actual">April 4, 2016</primary_completion_date>
  <phase>Phase 2</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, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
    <description>For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Event Rate = No. of Events*365.25 / (Follow-up date - Date of randomization + 1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
    <description>For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Event Rate = No. of Events*365.25 / (Follow-up date - Date of randomization + 1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Moderate or Severe Exacerbation</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annual Exacerbation Rate of Moderate and Severe Exacerbations</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
    <description>For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
    <description>For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
    <description>For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
    <description>The EXACT for Respiratory Symptoms (E-RS) scale is a derivative instrument comprising a subset of 11 of the EXACT items to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C])</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
    <description>The SGRQ-C is a modified version of the St. George's Respiratory Questionnaire, which has been developed to measure the impact of respiratory disease on health status. The SGRQ-C includes 14 questions in 3 domains: symptoms; activity; and impacts. Scores range from 0 to 100 with higher scores indicating benefit. Change in total score from pre study-treatment baseline to Week 12 end of treatment visit are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dyspnea (Transitional Dyspnea Index (TDI) Score)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
    <description>The Baseline/Transitional Dyspnea Index (BDI/TDI) provides a multidimensional measure of dyspnea in relation to activities of daily living. The BDI provides a measure of dyspnoea at a single state, the baseline, and the TDI evaluates changes in dyspnoea from the baseline state. The instrument consists of three components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these three components are rated in five grades from 0 (severe) to 4 (unimpaired), and are summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea are rated for each component by seven grades from -3 (major deterioration) to +3 (major improvement), and are added to form a total TDI score from -9 to +9. Positive scores indicate an improvement, and a change from the BDI or a difference between treatments of 1 point has been estimated to constitute the minimum clinically important difference.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Expiratory Volume in 1 Second (FEV1)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Vital Capacity (FVC)</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough FEV1/FVC Ratio</measure>
    <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">213</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease COPD</condition>
  <arm_group>
    <arm_group_label>AZD7624</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Active treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Comparator</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD7624 1.0 mg</intervention_name>
    <description>Inhaled AZD7624 solution, 11 mg/mL</description>
    <arm_group_label>AZD7624</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Inhaled placebo solution</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of signed and dated written informed consent prior to any study specific&#xD;
             procedures.&#xD;
&#xD;
          -  Male and females aged 40-85 years. Females must have a negative pregnancy test at&#xD;
             Visit 1, must not be lactating and must be of non-childbearing potential. Males must&#xD;
             be surgically sterile or agree to use an acceptable method of contraception for the&#xD;
             duration of the study and for 3 months after the last dose of investigational product&#xD;
             to prevent pregnancy in a partner.&#xD;
&#xD;
          -  A weight of ≥50 kg.&#xD;
&#xD;
          -  Diagnosis of COPD for more than 1 year at Visit 1, according to the Global Initiative&#xD;
             for Chronic Obstructive Lung Disease (GOLD) 2014 guidelines.&#xD;
&#xD;
          -  COPD maintenance treatment with at least ICS/LABA for at least 2 months prior to&#xD;
             enrolment to be continued unchanged during the study.&#xD;
&#xD;
          -  A post-bronchodilator FEV1/FVC &lt;0.70 and a post-bronchodilator FEV1 ≤70% of the&#xD;
             predicted normal value. Documented history of 2 or more moderate to severe COPD&#xD;
             exacerbations within 12 months of randomisation, but not within the last 6 weeks&#xD;
             before randomisation.&#xD;
&#xD;
          -  Current or ex-smokers with a smoking history of at least 10 pack-years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Involvement in the planning and conduct of the study.&#xD;
&#xD;
          -  Previous randomisation in the present study.&#xD;
&#xD;
          -  Participation in another clinical study with any investigational medicinal product&#xD;
             within 3 months of randomisation. Previously intake of any p38 inhibitor.&#xD;
&#xD;
          -  Participation in, or scheduled for an intensive COPD rehabilitation programme at any&#xD;
             time during the study.&#xD;
&#xD;
          -  Planned in-patient surgery or hospitalisation during the study.&#xD;
&#xD;
          -  Significant disease or disorder other than COPD which, may either put the patient at&#xD;
             risk because of participation in the study, or influence the results of the study, or&#xD;
             the patient's ability to participate in the study. Asthma as a primary or main&#xD;
             diagnosis according to the Global Initiative for Asthma (GINA) guidelines (GINA 2013)&#xD;
             or other accepted guidelines.&#xD;
&#xD;
          -  A clinically relevant abnormal findings in clinical chemistry, haematology and&#xD;
             urinalysis.&#xD;
&#xD;
          -  Plasma myoglobin and CK above the upper reference range of the analysing laboratory at&#xD;
             randomization.&#xD;
&#xD;
          -  A clinically relevant abnormal findings in physical examination, pulse or blood&#xD;
             pressure.&#xD;
&#xD;
          -  A positive result on screening for serum hepatitis B hepatitis C and Human&#xD;
             Immunodeficiency Virus (HIV).&#xD;
&#xD;
          -  History or family history of muscle diseases. Abnormal vital signs, defined as&#xD;
             Systolic Blood Pressure (SBP) above 140 mmHg if &lt;60 years of age and above 150 mmHg if&#xD;
             ≥60 years of age; Diastolic Blood Pressure (DBP) above 90 mmHg; Pulse &lt;50 or &gt;100 bpm.&#xD;
&#xD;
          -  Prolonged QTcF &gt;450 ms or family history of long QT syndrome or sudden death at young&#xD;
             age. PR(PQ) interval of clinical significance, PR(PQ) &gt; 250 ms.&#xD;
&#xD;
          -  Intermittent AV block of 2nd and 3rd degree or AV dissociation.&#xD;
&#xD;
          -  Patients with a QRS duration &gt;120 ms.&#xD;
&#xD;
          -  Patients with persistent, and/or recurrent symptomatic tachyarrhythmias, as well as&#xD;
             patients with an implantable cardioverter-defibrillator (ICD) or a permanent&#xD;
             pacemaker.&#xD;
&#xD;
          -  Patients with recent Cardiovascular (CV) events or unstable CV disease or a myocardial&#xD;
             infarction or stroke within 6 months of screening. History of hospitalization within&#xD;
             12 months caused by heart failure or a diagnosis of heart failure higher than New York&#xD;
             Heart Association (NYHA) class II.&#xD;
&#xD;
          -  History of severe allergy/hypersensitivity or ongoing clinically important&#xD;
             allergy/hypersensitivity or history of hypersensitivity to drugs with a similar&#xD;
             chemical structure or class to AZD7624.&#xD;
&#xD;
          -  Any exacerbation or respiratory infection within 6 weeks of randomization.&#xD;
&#xD;
          -  Plasma donation within one month of Visit 1, or any blood donation/blood loss &gt;500 mL&#xD;
             during the 3 months prior to Visit 1.&#xD;
&#xD;
          -  History of, or current alcohol or drug abuse.&#xD;
&#xD;
          -  Treatment with any GCS (apart from prescribed steroids at run-in) within 6 weeks of&#xD;
             Visit 3 regardless of indication.&#xD;
&#xD;
          -  Treatment with strong CYP3A inhibitors within 4 weeks prior to randomisation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Naimish Patel, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca R&amp;D Boston</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Barry Make, MD, FCCP, FACVPR</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Jewish Health, Denver, United States</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90036</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30310</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Blue Ridge</city>
        <state>Georgia</state>
        <zip>30513</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Larchmont</city>
        <state>New York</state>
        <zip>10538</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wilmington</city>
        <state>North Carolina</state>
        <zip>28401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Akron</city>
        <state>Ohio</state>
        <zip>44302</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45459</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Erie</city>
        <state>Pennsylvania</state>
        <zip>16508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gaffney</city>
        <state>South Carolina</state>
        <zip>29340</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rock Hill</city>
        <state>South Carolina</state>
        <zip>29732</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kingwood</city>
        <state>Texas</state>
        <zip>77339</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1414AIF</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Caba</city>
        <zip>C1425BEN</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ciudad Autónoma de Bs. As.</city>
        <zip>1426</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Quilmes</city>
        <zip>B1878FNR</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Miguel de Tucuman</city>
        <zip>4000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santiago</city>
        <zip>7980378</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santiago</city>
        <zip>8380453</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Talcahuano</city>
        <zip>4270918</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>Assen</city>
        <zip>9401 RK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Heerlen</city>
        <zip>6419 PC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nijmegen</city>
        <zip>6525 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Zutphen</city>
        <zip>7207 AE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lima</city>
        <zip>L 41</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lima</city>
        <zip>LIMA 21</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Amanzimtoti</city>
        <zip>4126</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cape Town</city>
        <zip>7764</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Johannesburg</city>
        <zip>1818</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Johannesburg</city>
        <zip>2001</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Mount Edgecombe</city>
        <zip>4302</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Parktown West</city>
        <zip>2193</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Chile</country>
    <country>Netherlands</country>
    <country>Peru</country>
    <country>South Africa</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>September 1, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <results_first_submitted>March 30, 2017</results_first_submitted>
  <results_first_submitted_qc>March 16, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">April 18, 2018</results_first_posted>
  <last_update_submitted>April 26, 2018</last_update_submitted>
  <last_update_submitted_qc>April 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic Obstructive Pulmonary Disease</keyword>
  <keyword>COPD patients</keyword>
  <keyword>Exacerbations</keyword>
  <keyword>ICS</keyword>
  <keyword>LABA</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>AZD7624</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was a multi-centre study conducted at 39 study centres in 6 countries: Argentina (37.7% of the patients); United States (34.4%) Peru (9%) Chile (6.6%) The Netherlands (6.1%) and South Africa (6.1%) A seasonal recruitment strategy was undertaken where patients were recruited in the fall and winter months of the geographic locality.</recruitment_details>
      <pre_assignment_details>327 patients signed informed consent, of which 213 patients were randomised. The majority of the 114 not randomised were screening failures</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>AZD7624</title>
          <description>Active treatment 2 x 0.5mg inhalation qd</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Matching placebo comparator</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="108"/>
                <participants group_id="P2" count="105"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="93"/>
                <participants group_id="P2" count="91"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawn due to physician decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Completion status not recorded</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Illness in family member</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>One patient was excluded from the Full Analysis Set due to lack of source data and GCP compliance issues.</population>
      <group_list>
        <group group_id="B1">
          <title>AZD7624</title>
          <description>Active treatment 2 x 0.5mg inhalation qd</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Matching placebo comparator</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="107"/>
            <count group_id="B2" value="105"/>
            <count group_id="B3" value="212"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="54"/>
                    <measurement group_id="B3" value="103"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="58"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="109"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="65.4" spread="8.73"/>
                    <measurement group_id="B2" value="64.2" spread="8.67"/>
                    <measurement group_id="B3" value="64.8" spread="8.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="76"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="69"/>
                    <measurement group_id="B3" value="136"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="66"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="131"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="81"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <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="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="85"/>
                    <measurement group_id="B2" value="88"/>
                    <measurement group_id="B3" value="173"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms</title>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms</title>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="5" upper_limit="NA">Too few events were observed in the treatment group for the estimation of median using Kaplan-Meier methodology.&#xD;
Too few events were observed for the estimation of the upper limit of the full range.</measurement>
                    <measurement group_id="O2" value="118.0" lower_limit="4" upper_limit="NA">Too few events were observed for the estimation of the upper limit of the full range.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>H0: Hazard Ratio (AZD7624/placebo) equals 1 vs. H1: Hazard Ratio does not equal 1.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2371</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.39</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.81</ci_lower_limit>
            <ci_upper_limit>2.40</ci_upper_limit>
            <estimate_desc>A hazard ratio greater than 1 indicates a higher rate of incidence in the AZD7624 group.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo)</title>
        <description>For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Event Rate = No. of Events*365.25 / (Follow-up date - Date of randomization + 1).</description>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo)</title>
          <description>For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Event Rate = No. of Events*365.25 / (Follow-up date - Date of randomization + 1).</description>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>Events / year</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.16" spread="0.80"/>
                    <measurement group_id="O2" value="1.62" spread="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.249</p_value>
            <method>regression, negative binomial</method>
            <param_type>Rate Ratio</param_type>
            <param_value>1.33</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.33</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.82</ci_lower_limit>
            <ci_upper_limit>2.16</ci_upper_limit>
            <estimate_desc>A hazard ratio greater than 1 indicates a higher rate of incidence in the AZD7624 group.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause)</title>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause)</title>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="5" upper_limit="NA">Too few events were observed in the treatment group for the estimation of median using Kaplan-Meier methodology.&#xD;
Too few events were observed for the estimation of the upper limit of the full range.</measurement>
                    <measurement group_id="O2" value="118.0" lower_limit="4" upper_limit="NA">Too few events were observed for the estimation of the upper limit of the full range.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1261</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.49</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.89</ci_lower_limit>
            <ci_upper_limit>2.50</ci_upper_limit>
            <estimate_desc>A hazard ratio greater than 1 indicates a higher rate of incidence in the AZD7624 group.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause)</title>
        <description>For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Event Rate = No. of Events*365.25 / (Follow-up date - Date of randomization + 1).</description>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause)</title>
          <description>For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Event Rate = No. of Events*365.25 / (Follow-up date - Date of randomization + 1).</description>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>Events / year</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.17" spread="0.80"/>
                    <measurement group_id="O2" value="1.55" spread="0.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.157</p_value>
            <method>regression, negative binomial</method>
            <param_type>Rate ratio</param_type>
            <param_value>1.40</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.33</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.88</ci_lower_limit>
            <ci_upper_limit>2.21</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Moderate or Severe Exacerbation</title>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Moderate or Severe Exacerbation</title>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="5" upper_limit="NA">Too few events were observed in the treatment group for the estimation of median using Kaplan-Meier methodology.&#xD;
Too few events were observed for the estimation of the upper limit of the full range.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="4" upper_limit="NA">Too few events were observed in the placebo group for the estimation of median using Kaplan-Meier methodology.&#xD;
Too few events were observed for the estimation of the upper limit of the full range.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1529</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.53</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.85</ci_lower_limit>
            <ci_upper_limit>2.76</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annual Exacerbation Rate of Moderate and Severe Exacerbations</title>
        <description>For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).</description>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Exacerbation Rate of Moderate and Severe Exacerbations</title>
          <description>For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).</description>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>Exacerbations / year</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.12" spread="0.78"/>
                    <measurement group_id="O2" value="1.42" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.129</p_value>
            <method>regression, negative binomial</method>
            <param_type>rate ratio</param_type>
            <param_value>1.50</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.40</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.89</ci_lower_limit>
            <ci_upper_limit>2.52</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)</title>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)</title>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="6" upper_limit="NA">Too few events were observed in the treatment group for the estimation of median using Kaplan-Meier methodology.&#xD;
Too few events were observed for the estimation of the upper limit of the full range.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="4" upper_limit="NA">Too few events were observed in the placebo group for the estimation of median using Kaplan-Meier methodology.&#xD;
Too few events were observed for the estimation of the upper limit of the full range.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.8543</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.93</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.43</ci_lower_limit>
            <ci_upper_limit>2.01</ci_upper_limit>
            <estimate_desc>A hazard ratio greater than 1 indicates a higher rate of incidence in the AZD7624 group.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)</title>
        <description>For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).</description>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)</title>
          <description>For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).</description>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>Exacerbations / year</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.23" spread="0.39"/>
                    <measurement group_id="O2" value="1.09" spread="0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.751</p_value>
            <method>regression, negative binomial</method>
            <param_type>rate ratio</param_type>
            <param_value>1.12</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.41</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.55</ci_lower_limit>
            <ci_upper_limit>2.29</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary)</title>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary)</title>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="3" upper_limit="NA">Too few events were observed in the treatment group for the estimation of median using Kaplan-Meier methodology.&#xD;
Too few events were observed for the estimation of the upper limit of the full range.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="2" upper_limit="NA">Too few events were observed in the placebo group for the estimation of median using Kaplan-Meier methodology.&#xD;
Too few events were observed for the estimation of the upper limit of the full range.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.5381</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.86</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.54</ci_lower_limit>
            <ci_upper_limit>1.38</ci_upper_limit>
            <estimate_desc>A hazard ratio greater than 1 indicates a higher rate of incidence in the AZD7624 group.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary)</title>
        <description>For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).</description>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary)</title>
          <description>For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.&#xD;
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).</description>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>Exacerbations / year</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.96" spread="0.54"/>
                    <measurement group_id="O2" value="2.33" spread="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.440</p_value>
            <method>regression, negative binomial</method>
            <param_type>rate ratio</param_type>
            <param_value>0.84</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.19</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.55</ci_lower_limit>
            <ci_upper_limit>1.30</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary)</title>
        <description>The EXACT for Respiratory Symptoms (E-RS) scale is a derivative instrument comprising a subset of 11 of the EXACT items to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.</description>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary)</title>
          <description>The EXACT for Respiratory Symptoms (E-RS) scale is a derivative instrument comprising a subset of 11 of the EXACT items to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.</description>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. One further patient was not included in the analysis due to missing covariate data.</population>
          <units>scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.21" spread="0.88"/>
                    <measurement group_id="O2" value="0.17" spread="0.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.5474</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.37</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.60</ci_lower_limit>
            <ci_upper_limit>0.85</ci_upper_limit>
            <estimate_desc>LSMean difference for overall treatment effect. Negative values for a difference show AZD7624 to have a favourable outcome compared to Placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C])</title>
        <description>The SGRQ-C is a modified version of the St. George's Respiratory Questionnaire, which has been developed to measure the impact of respiratory disease on health status. The SGRQ-C includes 14 questions in 3 domains: symptoms; activity; and impacts. Scores range from 0 to 100 with higher scores indicating benefit. Change in total score from pre study-treatment baseline to Week 12 end of treatment visit are reported.</description>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C])</title>
          <description>The SGRQ-C is a modified version of the St. George's Respiratory Questionnaire, which has been developed to measure the impact of respiratory disease on health status. The SGRQ-C includes 14 questions in 3 domains: symptoms; activity; and impacts. Scores range from 0 to 100 with higher scores indicating benefit. Change in total score from pre study-treatment baseline to Week 12 end of treatment visit are reported.</description>
          <population>Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.03" spread="19.574"/>
                    <measurement group_id="O2" value="-5.11" spread="17.809"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.6352</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.83</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.62</ci_lower_limit>
            <ci_upper_limit>4.29</ci_upper_limit>
            <estimate_desc>LSMean difference for overall treatment effect. Positive values for a difference show AZD7624 to have a favourable outcome compared to Placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Dyspnea (Transitional Dyspnea Index (TDI) Score)</title>
        <description>The Baseline/Transitional Dyspnea Index (BDI/TDI) provides a multidimensional measure of dyspnea in relation to activities of daily living. The BDI provides a measure of dyspnoea at a single state, the baseline, and the TDI evaluates changes in dyspnoea from the baseline state. The instrument consists of three components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these three components are rated in five grades from 0 (severe) to 4 (unimpaired), and are summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea are rated for each component by seven grades from -3 (major deterioration) to +3 (major improvement), and are added to form a total TDI score from -9 to +9. Positive scores indicate an improvement, and a change from the BDI or a difference between treatments of 1 point has been estimated to constitute the minimum clinically important difference.</description>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. Only patients with post-baseline TDI scores were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Dyspnea (Transitional Dyspnea Index (TDI) Score)</title>
          <description>The Baseline/Transitional Dyspnea Index (BDI/TDI) provides a multidimensional measure of dyspnea in relation to activities of daily living. The BDI provides a measure of dyspnoea at a single state, the baseline, and the TDI evaluates changes in dyspnoea from the baseline state. The instrument consists of three components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these three components are rated in five grades from 0 (severe) to 4 (unimpaired), and are summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea are rated for each component by seven grades from -3 (major deterioration) to +3 (major improvement), and are added to form a total TDI score from -9 to +9. Positive scores indicate an improvement, and a change from the BDI or a difference between treatments of 1 point has been estimated to constitute the minimum clinically important difference.</description>
          <population>The Full Analysis Set excluded one patient due to lack of source data and GCP compliance issues. Only patients with post-baseline TDI scores were included in the analysis.</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="102"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.41" spread="0.15"/>
                    <measurement group_id="O2" value="0.54" spread="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2694</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.12</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.34</ci_lower_limit>
            <ci_upper_limit>0.10</ci_upper_limit>
            <estimate_desc>LSMean difference for overall treatment effect. Positive values for a difference show AZD7624 to have a favourable outcome compared to Placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Expiratory Volume in 1 Second (FEV1)</title>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Expiratory Volume in 1 Second (FEV1)</title>
          <population>Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.</population>
          <units>Litres</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.003" spread="0.2555"/>
                    <measurement group_id="O2" value="-0.028" spread="0.2317"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.5144</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.02</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.03</ci_lower_limit>
            <ci_upper_limit>0.07</ci_upper_limit>
            <estimate_desc>LSMean difference for overall treatment effect. Positive values for a difference show AZD7624 to have a favourable outcome compared to Placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Vital Capacity (FVC)</title>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Vital Capacity (FVC)</title>
          <population>Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.</population>
          <units>Litres</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.045" spread="0.4017"/>
                    <measurement group_id="O2" value="-0.018" spread="0.3890"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.5416</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.02</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.10</ci_lower_limit>
            <ci_upper_limit>0.05</ci_upper_limit>
            <estimate_desc>LSMean difference for overall treatment effect. Positive values for a difference show AZD7624 to have a favourable outcome compared to Placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough FEV1/FVC Ratio</title>
        <time_frame>Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)</time_frame>
        <population>Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD7624</title>
            <description>Active treatment 2 x 0.5mg inhalation qd</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Matching placebo comparator</description>
          </group>
        </group_list>
        <measure>
          <title>Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough FEV1/FVC Ratio</title>
          <population>Full Analysis Set excluding one patient due to lack of source data and GCP compliance issues.</population>
          <units>L/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0077" spread="0.05269"/>
                    <measurement group_id="O2" value="-0.0072" spread="0.05255"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1965</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.01</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>0.02</ci_upper_limit>
            <estimate_desc>LSMean difference for overall treatment effect. Positive values for a difference show AZD7624 to have a favourable outcome compared to Placebo</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Serious adverse events (SAEs) were collected from informed consent throughout the study until follow-up (Week 14). Adverse events (AEs) were collected from Visit 2 (start of OCS treatment) throughout the study until follow-up (Week 14).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>AZD7624</title>
          <description>Active treatment 2 x 0.5mg inhalation qd</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Matching placebo comparator</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 18.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Coronary artery occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Biliary colic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA version 18.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="71" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="48" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="105"/>
              </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>Ziad Taib</name_or_title>
      <organization>AstraZeneca</organization>
      <phone>+46 708 46 73 56</phone>
      <email>ziad.taib@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/NCT02238483
org study id: D2550C00005
secondary id: 2014-001053-16
nct id: NCT02238483
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine whether AZD7624 can reduce acute Chronic
      Obstructive Pulmonary Disease (COPD) exacerbations in patients on COPD maintenance therapy
      with a history of frequent acute exacerbations.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
measure: Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
description: For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below.
Annual Event Rate = No. of Events*365.25 / (Follow-up date - Date of randomization + 1).
measure: Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
measure: Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
description: For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below.
Annual Event Rate = No. of Events*365.25 / (Follow-up date - Date of randomization + 1).
measure: Time to First Moderate or Severe Exacerbation
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
measure: Annual Exacerbation Rate of Moderate and Severe Exacerbations
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
description: For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).
measure: Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
measure: Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
description: For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).
measure: Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
measure: Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
description: For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below.
Annual Exacerbation Rate = No. of Exacerbations*365.25 / (Follow-up date - Date of randomization + 1).
measure: Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
description: The EXACT for Respiratory Symptoms (E-RS) scale is a derivative instrument comprising a subset of 11 of the EXACT items to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.
measure: Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C])
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
description: The SGRQ-C is a modified version of the St. George's Respiratory Questionnaire, which has been developed to measure the impact of respiratory disease on health status. The SGRQ-C includes 14 questions in 3 domains: symptoms; activity; and impacts. Scores range from 0 to 100 with higher scores indicating benefit. Change in total score from pre study-treatment baseline to Week 12 end of treatment visit are reported.
measure: Dyspnea (Transitional Dyspnea Index (TDI) Score)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
description: The Baseline/Transitional Dyspnea Index (BDI/TDI) provides a multidimensional measure of dyspnea in relation to activities of daily living. The BDI provides a measure of dyspnoea at a single state, the baseline, and the TDI evaluates changes in dyspnoea from the baseline state. The instrument consists of three components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these three components are rated in five grades from 0 (severe) to 4 (unimpaired), and are summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea are rated for each component by seven grades from -3 (major deterioration) to +3 (major improvement), and are added to form a total TDI score from -9 to +9. Positive scores indicate an improvement, and a change from the BDI or a difference between treatments of 1 point has been estimated to constitute the minimum clinically important difference.
measure: Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Expiratory Volume in 1 Second (FEV1)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
measure: Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough Forced Vital Capacity (FVC)
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
measure: Pulmonary Function Measured as Changes From Baseline (Post-bronchodilator at Visit 3) in Trough FEV1/FVC Ratio
time frame: Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)
arm group label: AZD7624
arm group type: Experimental
description: Active treatment
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo Comparator
intervention type: Drug
intervention name: AZD7624 1.0 mg
description: Inhaled AZD7624 solution, 11 mg/mL
arm group label: AZD7624
intervention type: Drug
intervention name: Placebo
description: Inhaled placebo solution
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: No
last name: Naimish Patel, MD, PhD
role: Study Director
affiliation: AstraZeneca R&D Boston
last name: Barry Make, MD, FCCP, FACVPR
role: Principal Investigator
affiliation: National Jewish Health, Denver, United States
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country: Argentina
country: Chile
country: Netherlands
country: Peru
country: South Africa
country: United States
country: Germany
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: AZD7624
participant flow: 
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reported events: 
certain agreements: 
point of contact: 