<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/NCT02971293</url>
  </required_header>
  <id_info>
    <org_study_id>D6640C00004</org_study_id>
    <nct_id>NCT02971293</nct_id>
  </id_info>
  <brief_title>Efficacy, Pharmacokinetics (PK), Safety and Tolerability Study of Inhaled AZD8871</brief_title>
  <official_title>A Phase IIa, Randomised, Multi-Centre, Double-Blind, Placebo-Controlled, 3 Periods, Crossover Study to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of Inhaled AZD8871 Administered Once Daily for 2 Weeks in Patients With Moderate to Severe COPD.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Parexel</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study to evaluate the effects of AZD8871 in patients with COPD. Adult male or&#xD;
      female patients with moderate to severe COPD, who agree to be in this study, will receive 3&#xD;
      treatments, i.e. 2 different doses of AZD8871 and placebo (dummy medication containing no&#xD;
      drug) at once a day for 2 weeks, in a random order. To make the comparison between AZD8871&#xD;
      and placebo as fair as possible, this study is &quot;double blinded.&quot; This means that neither&#xD;
      patient nor the study doctor will know in which order the 3 treatments will be given. This&#xD;
      study will include patients who are between 40 and 80 years of age. In total there will be 42&#xD;
      patients participating in this study at two study centers in the United Kingdom and Germany.&#xD;
      The study will have a total of 12 visits for each patient spanning for a period of 4 to 6&#xD;
      months. The study is anticipated to run for approximately 8 months and should not exceed 10&#xD;
      months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a proof-of-concept, randomised, double-blind, placebo-controlled, 3-way, complete&#xD;
      crossover William's design, multiple dose study to investigate the efficacy, PK, safety, and&#xD;
      tolerability of 2 dose levels of AZD8871 and placebo, administered using a dry powder inhaler&#xD;
      (DPI) device once daily, for 2 weeks, in patients with moderate to severe COPD. AZD8871 is a&#xD;
      new chemical entity with the combined properties of a LAMA and a LABA in a single molecule.&#xD;
      AZD8871 is being developed as an inhaled long-acting bronchodilator for the maintenance&#xD;
      treatment of COPD.&#xD;
&#xD;
      The objective of the study is to assess the efficacy, safety and PK of AZD8871 after a 14-day&#xD;
      treatment period at 2 different doses in patients with moderate to severe COPD. The target&#xD;
      population includes male and female (non-childbearing potential) adult patients with clinical&#xD;
      diagnosis of moderate to severe COPD. The crossover design has been chosen to avoid&#xD;
      inter-patient variability and optimize sample size. By randomly assigning treatment sequence,&#xD;
      differences in baseline characteristics of the treatment groups will be minimised. The&#xD;
      inclusion of a placebo arm is considered the most reliable method to minimise patient and&#xD;
      Investigator bias. The proposed dose levels of AZD8871 in this study are 100 and 600 µg of&#xD;
      AZD8871 given by inhalation once daily for 14 days through a single dose DPI. Doses have been&#xD;
      selected based on the safety, tolerability, PK and pharmacodynamics (PD) information&#xD;
      generated in previous clinical trials with AZD8871. The wash-out period proposed for this&#xD;
      current study is a minimum of 28 days and up to 35 days in order to avoid any carry over&#xD;
      effect between periods. The broad dose range selected (6 fold range from 100 to 600 µg) has&#xD;
      been chosen to span the likely therapeutic dose and facilitate the dose selection for future&#xD;
      studies. Considering the expected efficacy in patients with COPD and the available data to&#xD;
      date, it is anticipated the benefits will outweigh the risks and support the continued&#xD;
      investigation of AZD8871 in clinical studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 15, 2016</start_date>
  <completion_date type="Actual">August 18, 2017</completion_date>
  <primary_completion_date type="Actual">August 18, 2017</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)</measure>
    <time_frame>On Day 15</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 15</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Single Dose)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.</time_frame>
    <description>Observed maximum concentration, taken directly from the individual concentration-time curve, on Day 1 of each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.</time_frame>
    <description>Observed maximum concentration, taken directly from the individual concentration-time curve, on Day 14 of each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Single Dose)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.</time_frame>
    <description>Time to reach maximum concentration taken directly from the individual concentration-time curve on Day 1 of each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.</time_frame>
    <description>Time to reach maximum concentration taken directly from the individual concentration-time curve on Day 14 of each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast of AZD8871 and Its Metabolites (Single Dose)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.</time_frame>
    <description>Area under the plasma concentration-curve from time zero to the last quantifiable time point (24 hours post-dose) calculated on Day 1 of each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.</time_frame>
    <description>Area under the plasma concentration-curve from time zero to the last quantifiable time point (24 hours post-dose) calculated on Day 14 of each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-24 of AZD8871 and Its Metabolites (Single Dose)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.</time_frame>
    <description>Area under the plasma concentration-curve from time zero to 24 hours post-dose calculated on Day 1 of each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-24 of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.</time_frame>
    <description>Area under the plasma concentration-curve from time zero to 24 hours post-dose calculated on Day 14 of each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio for Cmax (RacCmax) of AZD8871 and Its Metabolites (Day 14)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 14.</time_frame>
    <description>Accumulation ratio for Cmax estimated as (Cmax on Day 14 / Cmax on Day 1) in each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio for AUC0-24 (RacAUC[0-24]) of AZD8871 and Its Metabolites (Day 14)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 14.</time_frame>
    <description>Accumulation ratio for AUC0-24 estimated as AUC0-24 on Day 14 / AUC0-24 on Day 1 in each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cavg of AZD8871 and Its Metabolites During a Dosing Interval (Day 14)</measure>
    <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.</time_frame>
    <description>Average plasma concentration during a dosing interval calculated on Day 14 of each treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Trough FEV1 at Day 1 (Single Dose)</measure>
    <time_frame>on Day 1</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Trough FEV1 at Day 8 (Pre-dose)</measure>
    <time_frame>on Day 8 (pre-dose)</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 8 (pre-dose)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Trough FEV1 Over the Treatment Duration (Days 1-15)</measure>
    <time_frame>Days 1-15</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 over the treatment duration from Day 1 to Day 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Peak FEV1 at Day 1 (Single Dose)</measure>
    <time_frame>on Day 1</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Peak FEV1 at Day 8</measure>
    <time_frame>on Day 8</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Peak FEV1 at Day 14</measure>
    <time_frame>on Day 14</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Peak FEV1 Over the Treatment Duration (Days 1-15)</measure>
    <time_frame>over the treatment duration (Days 1-15)</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in BCSS Questionnaire Total Score From Day 1 to Day 8 Post-treatment</measure>
    <time_frame>From Day 1 to Day 8 post-treatment</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change from baseline in Total score of the Breathlessness, Cough Sputum Scale (BCSS) questionnaire.&#xD;
The BCSS questionnaire is a 3-item patient-reported outcome measure. On a daily basis, patients rated 3 symptoms (breathlessness, cough and sputum) on a 5-point Likert scale (range 0-4, high scores indicating higher severity). The BCSS questionnaire Total Score is the sum of the 3 symptom scores, ranging from 0-12 (lowest-highest severity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in BCSS Questionnaire Total Score From Day 9 to Day 14 Post-treatment</measure>
    <time_frame>From Day 9 to Day 14 post-treatment</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change from baseline in Total score of the Breathlessness, Cough Sputum Scale (BCSS) questionnaire.&#xD;
The BCSS questionnaire is a 3-item patient-reported outcome measure. On a daily basis, patients rated 3 symptoms (breathlessness, cough and sputum) on a 5-point Likert scale (range 0-4, high scores indicating higher severity). The BCSS questionnaire Total Score is the sum of the 3 symptom scores, ranging from 0-12 (lowest-highest severity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Cough Individual Domain Score From Day 1 to Day 8 Post-treatment</measure>
    <time_frame>From Day 1 to Day 8 post-treatment</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire cough individual domain scores.&#xD;
On a daily basis, patients rated cough symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Cough Individual Domain Score From Day 9 to Day 14 Post-treatment</measure>
    <time_frame>From Day 9 to Day 14 post-treatment</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire cough individual domain scores.&#xD;
On a daily basis, patients rated cough symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Breathlessness Individual Domain Score From Day 1 to Day 8 Post-treatment</measure>
    <time_frame>From Day 1 to Day 8 post-treatment</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire breathlessness individual domain scores.&#xD;
On a daily basis, patients rated breathlessness symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Breathlessness Individual Domain Score From Day 9 to Day 14 Post-treatment</measure>
    <time_frame>From Day 9 to Day 14 post-treatment</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire breathlessness individual domain scores.&#xD;
On a daily basis, patients rated breathlessness symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Sputum Individual Domain Score From Day 1 to Day 8 Post-treatment</measure>
    <time_frame>From Day 1 to Day 8 post-treatment</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire sputum individual domain scores.&#xD;
On a daily basis, patients rated sputum symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Sputum Individual Domain Score From Day 9 to Day 14 Post-treatment</measure>
    <time_frame>From Day 9 to Day 14 post-treatment</time_frame>
    <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire sputum individual domain scores.&#xD;
On a daily basis, patients rated sputum symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease COPD</condition>
  <arm_group>
    <arm_group_label>AZD8871 100 µg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects will receive AZD8871 100 µg once daily, by dry powder inhaler (DPI) device. The treatment will be administered via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo will be administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient will receive one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AZD8871 600 µg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects will receive AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD8871 100 µg</intervention_name>
    <description>The subjects will receive one dose of AZD8871 100 µg single dose DPI.</description>
    <arm_group_label>AZD8871 100 µg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD8871 600 µg</intervention_name>
    <description>The subjects will receive AZD8871, 600 µg single dose DPI.</description>
    <arm_group_label>AZD8871 600 µg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The subject will receive Placebo single dose DPI.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient who provided of informed consent prior to any study-specific procedures&#xD;
&#xD;
          2. Male or female 40 to 80 years of age (both inclusive) at Screening (Visit 1). A female&#xD;
             is eligible to enter and participate in the study if she is of non-childbearing&#xD;
             potential.&#xD;
&#xD;
             Note: A female is considered to be of non-childbearing potential if she meets one of&#xD;
             the following criteria:&#xD;
&#xD;
               -  Permanently or surgically sterilised, including hysterectomy and/or bilateral&#xD;
                  oophorectomy and/or bilateral salpingectomy&#xD;
&#xD;
               -  Post-menopausal; aged &lt;50 years and amenorrhoeic for 12 months or more following&#xD;
                  cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and&#xD;
                  follicle stimulating hormone (FSH) levels in the post-menopausal range of the&#xD;
                  local laboratory.&#xD;
&#xD;
               -  Post-menopausal; aged ≥50 years and amenorrhoeic for 12 months or more, following&#xD;
                  cessation of all exogenous hormonal treatments.&#xD;
&#xD;
          3. Male patient should use a condom and spermicide to prevent pregnancy and drug exposure&#xD;
             of a partner, regardless of the gender or childbearing potential of the partner from&#xD;
             the day of the first administration of the investigational product (IP) until 3 months&#xD;
             after the last administration of the IP.&#xD;
&#xD;
          4. COPD Diagnosis: Patient with an established clinical history of COPD for more than 1&#xD;
             year at Screening, according to the Global Initiative for Chronic Obstructive Lung&#xD;
             Disease 2016 COPD guidelines.&#xD;
&#xD;
          5. Tobacco Use: Patient is a current or former smoker with a history of ≥10 pack-years of&#xD;
             cigarette smoking. A former smoker is defined as one who has stopped smoking for at&#xD;
             least 6 months prior to Screening.&#xD;
&#xD;
          6. Patient with post-bronchodilator FEV1/FVC (Forced vital capacity) ratio &lt;70% based on&#xD;
             the value reached after inhalation of salbutamol (400 µg) at Visit 2. If criterion is&#xD;
             not met, the test can be repeated at the latest, up to Day 14.&#xD;
&#xD;
          7. Patient with post-bronchodilator FEV1 that must be ≥40% and &lt;80% predicted normal&#xD;
             value and must also be &gt;750 mL at Visit 2. If criterion is not met, the test can be&#xD;
             repeated at the latest, up to Day 14.&#xD;
&#xD;
          8. Patient who fulfils reversibility criteria to salbutamol at Visit 2. Reversibility is&#xD;
             defined as ≥12% and ≥200 mL increase in FEV1 after inhalation of 4 puffs of&#xD;
             salbutamol. (400 µg). If criterion is not met, the test can be repeated at the latest,&#xD;
             up to Day 14.&#xD;
&#xD;
          9. Patient is willing and, in the opinion of the Investigator, able to change current&#xD;
             COPD therapy as required by the protocol and willing to use ipratropium Four times a&#xD;
             day (if needed, during run-in and wash-out periods) with or without Inhaled&#xD;
             corticosteroid for maintenance therapy of COPD and as needed rescue salbutamol from&#xD;
             Visit 1 up Visit 11.&#xD;
&#xD;
         10. Patient is free from any clinically active disease other than COPD that may impact&#xD;
             study outcome, as determined by medical history, physical examination, laboratory&#xD;
             testing, and 12-lead ECG findings, at Screening.&#xD;
&#xD;
         11. Patient is willing to remain at the study centre as required per protocol to complete&#xD;
             all visit assessments.&#xD;
&#xD;
         12. Patient with body mass index (BMI) &lt;40 kg/m2 at the time of screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient previously enrolled in the present study.&#xD;
&#xD;
          2. Patient has significant diseases other than COPD, ie, disease or condition or an&#xD;
             abnormality in laboratory, ECG, medical history or physical examination which, in the&#xD;
             opinion of the Investigator, may put the patient at risk because of participation in&#xD;
             the study or may influence either the results of the study or the patient'spatient's&#xD;
             ability to participate in the study.&#xD;
&#xD;
          3. Childbearing potential female, pregnant or lactating.&#xD;
&#xD;
          4. Patient who, in the opinion of the Investigator, has a current diagnosis of asthma.&#xD;
&#xD;
          5. Patient has alpha-1 antitrypsin deficiency as the cause of COPD.&#xD;
&#xD;
          6. Patient has other active pulmonary disease such as active tuberculosis, lung cancer,&#xD;
             bronchiectasis sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary&#xD;
             pulmonary hypertension, or uncontrolled sleep apnoea. Allergic rhinitis is not&#xD;
             exclusionary.&#xD;
&#xD;
          7. Lung surgery for volume reduction or lung transplantation: Patient has undergone lung&#xD;
             volume reduction surgery, lobectomy, or bronchoscopic lung volume reduction&#xD;
             (endobronchial blockers, airway bypass, endobronchial valves, thermal vapour ablation,&#xD;
             biological sealants, massive pulmonary embolism and airway implants) within 1 year of&#xD;
             Screening (Visit 1).&#xD;
&#xD;
          8. Patient is using nocturnal positive pressure (eg, continuous positive airway pressure&#xD;
             or bi level positive airway pressure). Patient is using any non-invasive positive&#xD;
             pressure ventilation device.&#xD;
&#xD;
             Note: A patient using continuous positive airway pressure or bi level positive airway&#xD;
             pressure for Sleep Apnoea Syndrome is allowed in the study.&#xD;
&#xD;
          9. Patient has been hospitalised due to poorly controlled COPD within 3 months of&#xD;
             Screening.&#xD;
&#xD;
         10. Patient has acute worsening of COPD that requires treatment with corticosteroids or&#xD;
             antibiotics in the 6 week interval prior to Screening (Visit 1), or during the&#xD;
             Screening Period (between Visits 1 and 3).&#xD;
&#xD;
         11. Patient has had lower respiratory tract infections that required antibiotics within 6&#xD;
             weeks prior to Screening.&#xD;
&#xD;
         12. Patient cannot perform acceptable spirometry, ie, meet American Thoracic Society&#xD;
             (ATS)/European Respiratory Society (ERS) acceptability criteria.&#xD;
&#xD;
         13. Patient has changed their smoking status (ie, start or stop smoking) or initiation of&#xD;
             a smoking cessation program within 6 weeks prior to Screening.&#xD;
&#xD;
         14. Patient has participated in the acute phase of a pulmonary rehabilitation program&#xD;
             within 4 weeks prior to Screening or who will enter the acute phase of a pulmonary&#xD;
             rehabilitation program during the study. A patient in the maintenance phase of a&#xD;
             pulmonary rehabilitation program is not to be excluded.&#xD;
&#xD;
         15. Cardiac disease: Subject with significant cardiovascular disease cardiovascular&#xD;
             instability. Patient with heart rate &lt;50 beats per minute. Patient has clinically&#xD;
             significant uncontrolled hypertension as assessed by the investigator.&#xD;
&#xD;
         16. Neurological: Patient with seizures or history of seizures requiring anticonvulsants&#xD;
             within 12 months prior to Screening. Patient is taking selective serotonin reuptake&#xD;
             inhibitors or serotonin--norepinephrine reuptake inhibitors whose dose has not been&#xD;
             stable for at least 4 weeks prior to Screening, or exceeds the maximum recommended&#xD;
             dose.&#xD;
&#xD;
         17. Renal: Patient with symptomatic bladder neck obstruction, acute urinary retention or&#xD;
             symptomatic non-stable prostate hypertrophy. 35.23. Patient with a serum potassium&#xD;
             value &lt;3.5 mmol/L at Screening and on repeat testing. Note: however potassium&#xD;
             replacement and rescreening is allowed if serum potassium concentration was &lt;&#xD;
             3.5mmol/l at screening.&#xD;
&#xD;
         18. Others:&#xD;
&#xD;
               -  Any laboratory abnormality or suspicion of any clinically relevant disease or&#xD;
                  disorder (on history or examination), including uncontrolled hypertension or&#xD;
                  uncontrolled diabetes, which, in the opinion of the Investigator, may either put&#xD;
                  the patient at risk because of participation in the study, or influence the&#xD;
                  results or the patient's ability to participate in the study, or any other safety&#xD;
                  concerns in the opinion of the Investigator.&#xD;
&#xD;
               -  History of malignancy of any organ system, treated or untreated within the past 5&#xD;
                  years, with the exception of localized basal cell carcinoma of the skin&#xD;
&#xD;
               -  Patient with known narrow-angle glaucoma.&#xD;
&#xD;
               -  Patient has a history of hypersensitivity to β2-agonists, muscarinic&#xD;
                  anticholinergics or lactose/milk protein. Lactose intolerance is not an exclusion&#xD;
                  criterion.&#xD;
&#xD;
               -  The patient has a known or suspected history of alcohol or drug of abuse within&#xD;
                  the past 2-year period years or consuming more than 14 (female subjects) or 21&#xD;
                  (male subjects) units of alcohol a week, or shows positive for drugs of abuse and&#xD;
                  alcohol tests at screening and prior to randomization.&#xD;
&#xD;
               -  Patient who, in the opinion of the Investigator, would be unable to abstain from&#xD;
                  protocol-defined prohibited medications during the study.&#xD;
&#xD;
               -  Patient who received a live attenuated vaccination within 30 days prior to&#xD;
                  Screening.&#xD;
&#xD;
               -  Patient involved in the planning and/or conduct of the study (applies to both&#xD;
                  AstraZeneca staff and/or staff at the study site).&#xD;
&#xD;
               -  Patient treated with investigational drug or device in another clinical trial&#xD;
                  within the last 30 days or five half-lives (whichever is longer) prior to&#xD;
                  Screening.&#xD;
&#xD;
               -  Patient who donated or lost &gt;500 mL of blood and plasma within the previous 3&#xD;
                  months prior to screening.&#xD;
&#xD;
               -  Patient is unlikely to co-operate with the requirements of the study,&#xD;
                  instructions of the Principal Investigator., or have e-dairy completion rate of &lt;&#xD;
                  70% during the run in period.&#xD;
&#xD;
               -  Patient with known human immunodeficiency virus (HIV) infection or chronic&#xD;
                  hepatitis B or C infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dave Singh, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medicines Evaluation Unit, Manchester, United Kingdom</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rainard Fuhr, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>PAREXEL International GmbH EPCU Berlin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Berlin</city>
        <zip>14050</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Manchester</city>
        <zip>M23 9QZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&amp;studyid=4121&amp;filename=AZD8871%20D6640C00006%20Clinical%20Study%20Protocol%20(CSP)_redacted.pdf</url>
    <description>Related Info</description>
  </link>
  <link>
    <url>http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&amp;studyid=4121&amp;filename=azd8871-d6640c00004-redacted-sap-ed-1-3.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>October 28, 2016</study_first_submitted>
  <study_first_submitted_qc>November 18, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <results_first_submitted>August 10, 2018</results_first_submitted>
  <results_first_submitted_qc>June 16, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 18, 2019</results_first_posted>
  <last_update_submitted>June 16, 2019</last_update_submitted>
  <last_update_submitted_qc>June 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AZD8871</keyword>
  <keyword>long-acting muscarinic antagonist (LAMA)</keyword>
  <keyword>long-acting β2-agonist (LABA)</keyword>
  <keyword>inhaled long-acting bronchodilator</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>safety</keyword>
  <keyword>tolerability</keyword>
  <keyword>efficacy</keyword>
  <keyword>Phase IIa</keyword>
  <keyword>Muscarinic receptor antagonist β2 adrenoceptor agonist (MABA)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 16, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT02971293/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 26, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT02971293/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at two centres, one each in Germany and the UK. The first patient was enrolled in December 2016 and the last patient last visit was in August 2017.</recruitment_details>
      <pre_assignment_details>A total of 103 patients were screened; 42 patients were eligible to participate and were randomised.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Participants</title>
          <description>All subjects received AZD8871 100 µg, AZD8871 600 µg or placebo, once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.&#xD;
Each subject was randomized to one of three sequences in a 3-way, complete crossover William's design, and received all 3 treatments in turn, in three 14-day treatment periods, each (except the last one) followed by a wash-out period of 28-35 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis set: Includes all randomised participants who received at least one dose of investigational product.</population>
      <group_list>
        <group group_id="B1">
          <title>Overall Study Population</title>
          <description>Full analysis set: All randomised participants who received at least one dose of investigational product.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="42"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.6" spread="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 15</description>
        <time_frame>On Day 15</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 15</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
          <units>L</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.168" spread="0.037"/>
                    <measurement group_id="O2" value="0.267" spread="0.035"/>
                    <measurement group_id="O3" value="0.007" spread="0.036"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.020</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Single Dose)</title>
        <description>Observed maximum concentration, taken directly from the individual concentration-time curve, on Day 1 of each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Single Dose)</title>
          <description>Observed maximum concentration, taken directly from the individual concentration-time curve, on Day 1 of each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
          <units>pg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.05" spread="47.47"/>
                    <measurement group_id="O2" value="290.8" spread="36.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.796" spread="38.67"/>
                    <measurement group_id="O2" value="33.87" spread="33.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="187.7" spread="55.41"/>
                    <measurement group_id="O2" value="1016" spread="50.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</title>
        <description>Observed maximum concentration, taken directly from the individual concentration-time curve, on Day 14 of each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</title>
          <description>Observed maximum concentration, taken directly from the individual concentration-time curve, on Day 14 of each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
          <units>pg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.52" spread="45.69"/>
                    <measurement group_id="O2" value="381.8" spread="36.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.89" spread="39.41"/>
                    <measurement group_id="O2" value="63.17" spread="38.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="221.4" spread="69.96"/>
                    <measurement group_id="O2" value="1152" spread="55.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Single Dose)</title>
        <description>Time to reach maximum concentration taken directly from the individual concentration-time curve on Day 1 of each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Single Dose)</title>
          <description>Time to reach maximum concentration taken directly from the individual concentration-time curve on Day 1 of each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
          <units>h</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.93" lower_limit="0.42" upper_limit="2.00"/>
                    <measurement group_id="O2" value="1.46" lower_limit="0.48" upper_limit="2.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.92" lower_limit="0.93" upper_limit="4.83"/>
                    <measurement group_id="O2" value="2.02" lower_limit="1.00" upper_limit="4.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.94" lower_limit="1.92" upper_limit="6.00"/>
                    <measurement group_id="O2" value="3.98" lower_limit="3.92" upper_limit="6.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</title>
        <description>Time to reach maximum concentration taken directly from the individual concentration-time curve on Day 14 of each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</title>
          <description>Time to reach maximum concentration taken directly from the individual concentration-time curve on Day 14 of each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
          <units>h</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.93" lower_limit="0.42" upper_limit="1.00"/>
                    <measurement group_id="O2" value="1.00" lower_limit="0.50" upper_limit="2.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.96" lower_limit="0.98" upper_limit="3.95"/>
                    <measurement group_id="O2" value="2.00" lower_limit="0.98" upper_limit="3.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.92" lower_limit="0.00" upper_limit="4.00"/>
                    <measurement group_id="O2" value="4.02" lower_limit="3.90" upper_limit="6.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUClast of AZD8871 and Its Metabolites (Single Dose)</title>
        <description>Area under the plasma concentration-curve from time zero to the last quantifiable time point (24 hours post-dose) calculated on Day 1 of each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>AUClast of AZD8871 and Its Metabolites (Single Dose)</title>
          <description>Area under the plasma concentration-curve from time zero to the last quantifiable time point (24 hours post-dose) calculated on Day 1 of each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
          <units>pg*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="18"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="301.0" spread="54.52"/>
                    <measurement group_id="O2" value="1777" spread="40.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="18"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.06" spread="94.87"/>
                    <measurement group_id="O2" value="358.5" spread="32.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="18"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1414" spread="69.31"/>
                    <measurement group_id="O2" value="9299" spread="53.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUClast of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</title>
        <description>Area under the plasma concentration-curve from time zero to the last quantifiable time point (24 hours post-dose) calculated on Day 14 of each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>AUClast of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</title>
          <description>Area under the plasma concentration-curve from time zero to the last quantifiable time point (24 hours post-dose) calculated on Day 14 of each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
          <units>pg*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="539.2" spread="51.23"/>
                    <measurement group_id="O2" value="3156" spread="42.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="160.2" spread="64.39"/>
                    <measurement group_id="O2" value="935.9" spread="46.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1964" spread="93.81"/>
                    <measurement group_id="O2" value="13050" spread="52.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-24 of AZD8871 and Its Metabolites (Single Dose)</title>
        <description>Area under the plasma concentration-curve from time zero to 24 hours post-dose calculated on Day 1 of each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-24 of AZD8871 and Its Metabolites (Single Dose)</title>
          <description>Area under the plasma concentration-curve from time zero to 24 hours post-dose calculated on Day 1 of each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
          <units>pg*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="18"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="326.1" spread="49.18"/>
                    <measurement group_id="O2" value="1776" spread="40.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="18"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="135.6" spread="25.79"/>
                    <measurement group_id="O2" value="358.1" spread="32.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="15"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                    <measurement group_id="O2" value="10440" spread="49.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC0-24 of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</title>
        <description>Area under the plasma concentration-curve from time zero to 24 hours post-dose calculated on Day 14 of each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-24 of AZD8871 and Its Metabolites (Multiple Doses, Day 14)</title>
          <description>Area under the plasma concentration-curve from time zero to 24 hours post-dose calculated on Day 14 of each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations</population>
          <units>pg*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="538.4" spread="51.16"/>
                    <measurement group_id="O2" value="3152" spread="42.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="179.4" spread="38.81"/>
                    <measurement group_id="O2" value="933.8" spread="46.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3281" spread="66.13"/>
                    <measurement group_id="O2" value="13030" spread="52.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accumulation Ratio for Cmax (RacCmax) of AZD8871 and Its Metabolites (Day 14)</title>
        <description>Accumulation ratio for Cmax estimated as (Cmax on Day 14 / Cmax on Day 1) in each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 14.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Accumulation Ratio for Cmax (RacCmax) of AZD8871 and Its Metabolites (Day 14)</title>
          <description>Accumulation ratio for Cmax estimated as (Cmax on Day 14 / Cmax on Day 1) in each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.263" lower_limit="0.765" upper_limit="2.30"/>
                    <measurement group_id="O2" value="1.385" lower_limit="0.700" upper_limit="1.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.594" lower_limit="0.946" upper_limit="2.86"/>
                    <measurement group_id="O2" value="1.968" lower_limit="0.929" upper_limit="2.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.257" lower_limit="0.757" upper_limit="3.388"/>
                    <measurement group_id="O2" value="1.133" lower_limit="0.545" upper_limit="1.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accumulation Ratio for AUC0-24 (RacAUC[0-24]) of AZD8871 and Its Metabolites (Day 14)</title>
        <description>Accumulation ratio for AUC0-24 estimated as AUC0-24 on Day 14 / AUC0-24 on Day 1 in each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 14.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Accumulation Ratio for AUC0-24 (RacAUC[0-24]) of AZD8871 and Its Metabolites (Day 14)</title>
          <description>Accumulation ratio for AUC0-24 estimated as AUC0-24 on Day 14 / AUC0-24 on Day 1 in each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
          <units>pg*h/mL</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.893" lower_limit="1.06" upper_limit="3.86"/>
                    <measurement group_id="O2" value="1.878" lower_limit="1.09" upper_limit="2.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.576" lower_limit="1.10" upper_limit="2.44"/>
                    <measurement group_id="O2" value="2.721" lower_limit="1.41" upper_limit="3.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="15"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.24" lower_limit="1.24" upper_limit="1.24"/>
                    <measurement group_id="O2" value="1.326" lower_limit="0.713" upper_limit="1.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cavg of AZD8871 and Its Metabolites During a Dosing Interval (Day 14)</title>
        <description>Average plasma concentration during a dosing interval calculated on Day 14 of each treatment period.</description>
        <time_frame>Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.</time_frame>
        <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Cavg of AZD8871 and Its Metabolites During a Dosing Interval (Day 14)</title>
          <description>Average plasma concentration during a dosing interval calculated on Day 14 of each treatment period.</description>
          <population>Pharmacokinetic analysis set: defined as all patients in the safety analysis set who received at least 1 dose of AZD8871 (100 μg or 600 μg), had at least 1 evaluable parameter out of Cmax, AUC or AUClast for AZD8871, and were assumed not to be affected by factors such as protocol deviations.</population>
          <units>pg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AZD8871</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.44" spread="51.13"/>
                    <measurement group_id="O2" value="131.4" spread="42.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS191861</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.478" spread="38.81"/>
                    <measurement group_id="O2" value="38.94" spread="46.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>LAS34850</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="17"/>
                    <count group_id="O3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="136.7" spread="66.11"/>
                    <measurement group_id="O2" value="543.3" spread="52.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Trough FEV1 at Day 1 (Single Dose)</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 1</description>
        <time_frame>on Day 1</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trough FEV1 at Day 1 (Single Dose)</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 1</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
          <units>L</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.092" spread="0.029"/>
                    <measurement group_id="O2" value="0.161" spread="0.027"/>
                    <measurement group_id="O3" value="0.006" spread="0.028"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.002</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.011</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Trough FEV1 at Day 8 (Pre-dose)</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 8 (pre-dose)</description>
        <time_frame>on Day 8 (pre-dose)</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trough FEV1 at Day 8 (Pre-dose)</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 8 (pre-dose)</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
          <units>L</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.180" spread="0.033"/>
                    <measurement group_id="O2" value="0.232" spread="0.030"/>
                    <measurement group_id="O3" value="0.032" spread="0.031"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.201</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Trough FEV1 Over the Treatment Duration (Days 1-15)</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 over the treatment duration from Day 1 to Day 15</description>
        <time_frame>Days 1-15</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trough FEV1 Over the Treatment Duration (Days 1-15)</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 over the treatment duration from Day 1 to Day 15</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
          <units>L</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.146" spread="0.029"/>
                    <measurement group_id="O2" value="0.215" spread="0.027"/>
                    <measurement group_id="O3" value="0.016" spread="0.027"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effect: treatment, sequence, period, treatment*day. Repeat factor: day. Random effect: patient nested in sequence. Continuous covar: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effect: treatment, sequence, period, treatment*day. Repeat factor: day. Random effect: patient nested in sequence. Continuous covar: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.020</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effect: treatment, sequence, period, treatment*day. Repeat factor: day. Random effect: patient nested in sequence. Continuous covar: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Peak FEV1 at Day 1 (Single Dose)</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
        <time_frame>on Day 1</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peak FEV1 at Day 1 (Single Dose)</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
          <units>L</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.376" spread="0.026"/>
                    <measurement group_id="O2" value="0.469" spread="0.025"/>
                    <measurement group_id="O3" value="0.076" spread="0.025"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Peak FEV1 at Day 8</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
        <time_frame>on Day 8</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peak FEV1 at Day 8</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
          <units>L</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.486" spread="0.040"/>
                    <measurement group_id="O2" value="0.556" spread="0.037"/>
                    <measurement group_id="O3" value="0.136" spread="0.038"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.092</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Peak FEV1 at Day 14</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
        <time_frame>on Day 14</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peak FEV1 at Day 14</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
          <units>L</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.476" spread="0.037"/>
                    <measurement group_id="O2" value="0.522" spread="0.035"/>
                    <measurement group_id="O3" value="0.095" spread="0.036"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.279</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Peak FEV1 Over the Treatment Duration (Days 1-15)</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
        <time_frame>over the treatment duration (Days 1-15)</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peak FEV1 Over the Treatment Duration (Days 1-15)</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
          <units>L</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.438" spread="0.028"/>
                    <measurement group_id="O2" value="0.511" spread="0.027"/>
                    <measurement group_id="O3" value="0.102" spread="0.028"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effect: treatment, sequence, period, treatment*day. Repeat factor: day. Random effect: patient nested in sequence. Continuous covar: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effect: treatment, sequence, period, treatment*day. Repeat factor: day. Random effect: patient nested in sequence. Continuous covar: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effect: treatment, sequence, period, treatment*day. Repeat factor: day. Random effect: patient nested in sequence. Continuous covar: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in BCSS Questionnaire Total Score From Day 1 to Day 8 Post-treatment</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change from baseline in Total score of the Breathlessness, Cough Sputum Scale (BCSS) questionnaire.&#xD;
The BCSS questionnaire is a 3-item patient-reported outcome measure. On a daily basis, patients rated 3 symptoms (breathlessness, cough and sputum) on a 5-point Likert scale (range 0-4, high scores indicating higher severity). The BCSS questionnaire Total Score is the sum of the 3 symptom scores, ranging from 0-12 (lowest-highest severity).</description>
        <time_frame>From Day 1 to Day 8 post-treatment</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in BCSS Questionnaire Total Score From Day 1 to Day 8 Post-treatment</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change from baseline in Total score of the Breathlessness, Cough Sputum Scale (BCSS) questionnaire.&#xD;
The BCSS questionnaire is a 3-item patient-reported outcome measure. On a daily basis, patients rated 3 symptoms (breathlessness, cough and sputum) on a 5-point Likert scale (range 0-4, high scores indicating higher severity). The BCSS questionnaire Total Score is the sum of the 3 symptom scores, ranging from 0-12 (lowest-highest severity).</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.416" spread="0.216"/>
                    <measurement group_id="O2" value="-0.920" spread="0.198"/>
                    <measurement group_id="O3" value="-0.071" spread="0.205"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.205</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.002</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.060</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in BCSS Questionnaire Total Score From Day 9 to Day 14 Post-treatment</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change from baseline in Total score of the Breathlessness, Cough Sputum Scale (BCSS) questionnaire.&#xD;
The BCSS questionnaire is a 3-item patient-reported outcome measure. On a daily basis, patients rated 3 symptoms (breathlessness, cough and sputum) on a 5-point Likert scale (range 0-4, high scores indicating higher severity). The BCSS questionnaire Total Score is the sum of the 3 symptom scores, ranging from 0-12 (lowest-highest severity).</description>
        <time_frame>From Day 9 to Day 14 post-treatment</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in BCSS Questionnaire Total Score From Day 9 to Day 14 Post-treatment</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change from baseline in Total score of the Breathlessness, Cough Sputum Scale (BCSS) questionnaire.&#xD;
The BCSS questionnaire is a 3-item patient-reported outcome measure. On a daily basis, patients rated 3 symptoms (breathlessness, cough and sputum) on a 5-point Likert scale (range 0-4, high scores indicating higher severity). The BCSS questionnaire Total Score is the sum of the 3 symptom scores, ranging from 0-12 (lowest-highest severity).</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.491" spread="0.237"/>
                    <measurement group_id="O2" value="-1.191" spread="0.219"/>
                    <measurement group_id="O3" value="-0.030" spread="0.226"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.111</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.015</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Cough Individual Domain Score From Day 1 to Day 8 Post-treatment</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire cough individual domain scores.&#xD;
On a daily basis, patients rated cough symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
        <time_frame>From Day 1 to Day 8 post-treatment</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Cough Individual Domain Score From Day 1 to Day 8 Post-treatment</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire cough individual domain scores.&#xD;
On a daily basis, patients rated cough symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.186" spread="0.091"/>
                    <measurement group_id="O2" value="-0.287" spread="0.084"/>
                    <measurement group_id="O3" value="-0.134" spread="0.087"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.621</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.138</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.333</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Cough Individual Domain Score From Day 9 to Day 14 Post-treatment</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire cough individual domain scores.&#xD;
On a daily basis, patients rated cough symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
        <time_frame>From Day 9 to Day 14 post-treatment</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Cough Individual Domain Score From Day 9 to Day 14 Post-treatment</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire cough individual domain scores.&#xD;
On a daily basis, patients rated cough symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.160" spread="0.096"/>
                    <measurement group_id="O2" value="-0.445" spread="0.088"/>
                    <measurement group_id="O3" value="-0.123" spread="0.091"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.748</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.013</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Breathlessness Individual Domain Score From Day 1 to Day 8 Post-treatment</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire breathlessness individual domain scores.&#xD;
On a daily basis, patients rated breathlessness symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
        <time_frame>From Day 1 to Day 8 post-treatment</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Breathlessness Individual Domain Score From Day 1 to Day 8 Post-treatment</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire breathlessness individual domain scores.&#xD;
On a daily basis, patients rated breathlessness symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.122" spread="0.097"/>
                    <measurement group_id="O2" value="-0.377" spread="0.089"/>
                    <measurement group_id="O3" value="0.099" spread="0.092"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.064</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.030</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Breathlessness Individual Domain Score From Day 9 to Day 14 Post-treatment</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire breathlessness individual domain scores.&#xD;
On a daily basis, patients rated breathlessness symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
        <time_frame>From Day 9 to Day 14 post-treatment</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Breathlessness Individual Domain Score From Day 9 to Day 14 Post-treatment</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire breathlessness individual domain scores.&#xD;
On a daily basis, patients rated breathlessness symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.202" spread="0.108"/>
                    <measurement group_id="O2" value="-0.453" spread="0.100"/>
                    <measurement group_id="O3" value="0.106" spread="0.103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.018</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.047</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Sputum Individual Domain Score From Day 1 to Day 8 Post-treatment</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire sputum individual domain scores.&#xD;
On a daily basis, patients rated sputum symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
        <time_frame>From Day 1 to Day 8 post-treatment</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Sputum Individual Domain Score From Day 1 to Day 8 Post-treatment</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire sputum individual domain scores.&#xD;
On a daily basis, patients rated sputum symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.100" spread="0.070"/>
                    <measurement group_id="O2" value="-0.255" spread="0.064"/>
                    <measurement group_id="O3" value="-0.035" spread="0.066"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.477</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.014</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.084</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Sputum Individual Domain Score From Day 9 to Day 14 Post-treatment</title>
        <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire sputum individual domain scores.&#xD;
On a daily basis, patients rated sputum symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
        <time_frame>From Day 9 to Day 14 post-treatment</time_frame>
        <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>AZD8871 100 µg</title>
            <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O2">
            <title>AZD8871 600 µg</title>
            <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Sputum Individual Domain Score From Day 9 to Day 14 Post-treatment</title>
          <description>The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire sputum individual domain scores.&#xD;
On a daily basis, patients rated sputum symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).</description>
          <population>Full analysis set (FAS): all randomised patients who received at least one dose of the IP, irrespective of their protocol adherence and continued participation in the study.</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="34"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.122" spread="0.078"/>
                    <measurement group_id="O2" value="-0.297" spread="0.073"/>
                    <measurement group_id="O3" value="-0.011" spread="0.075"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 100 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.213</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of AZD8871 600 µg vs AZD8871 100 µg</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.046</p_value>
            <method>ANCOVA</method>
            <method_desc>Fixed effects: treatment, sequence, period. Random effect for patient nested within sequence. Continuous covariate: baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From screening to Follow-up/early termination Visit, 28 to 35 days after the last administration of investigational product (IP)</time_frame>
      <desc>All reported AEs, date of onset, date of resolution, Investigator's assessment of severity, outcome, action taken with IP, and relationship to the IP were listed.&#xD;
Non-Treatment-emergent adverse event (non-TEAE): any AE occurring before the first dose of IP, or &gt;30 days after the last dose TEAE: event occurring after first dose of IP or present prior to the first dose, but increasing in severity after IP administration.</desc>
      <group_list>
        <group group_id="E1">
          <title>AZD8871 100 µg</title>
          <description>The subjects received AZD8871 100 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
        </group>
        <group group_id="E2">
          <title>AZD8871 600 µg</title>
          <description>The subjects received AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>The placebo was administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient received one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abdominal wall abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease exacerbation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA version 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="39"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral upper respiratory tract infections</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="39"/>
                <counts group_id="E3" events="7" subjects_affected="4" subjects_at_risk="36"/>
              </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" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="36"/>
              </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>Publication and / or presentation whether complete or partial, of any part of the data or results of this study will not be allowed until global publication and study results disclosure by the sponsor as per EMA / FDA regulatory compliance obligations, and only after mutual agreement between the Investigator and AstraZeneca</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Ioannis Psallidas, MD, PhD</name_or_title>
      <organization>AstraZeneca</organization>
      <phone>1-877-240-9479</phone>
      <email>Information.centre@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/NCT02971293
org study id: D6640C00004
nct id: NCT02971293
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a study to evaluate the effects of AZD8871 in patients with COPD. Adult male or
      female patients with moderate to severe COPD, who agree to be in this study, will receive 3
      treatments, i.e. 2 different doses of AZD8871 and placebo (dummy medication containing no
      drug) at once a day for 2 weeks, in a random order. To make the comparison between AZD8871
      and placebo as fair as possible, this study is "double blinded." This means that neither
      patient nor the study doctor will know in which order the 3 treatments will be given. This
      study will include patients who are between 40 and 80 years of age. In total there will be 42
      patients participating in this study at two study centers in the United Kingdom and Germany.
      The study will have a total of 12 visits for each patient spanning for a period of 4 to 6
      months. The study is anticipated to run for approximately 8 months and should not exceed 10
      months.
This is a proof-of-concept, randomised, double-blind, placebo-controlled, 3-way, complete
      crossover William's design, multiple dose study to investigate the efficacy, PK, safety, and
      tolerability of 2 dose levels of AZD8871 and placebo, administered using a dry powder inhaler
      (DPI) device once daily, for 2 weeks, in patients with moderate to severe COPD. AZD8871 is a
      new chemical entity with the combined properties of a LAMA and a LABA in a single molecule.
      AZD8871 is being developed as an inhaled long-acting bronchodilator for the maintenance
      treatment of COPD.

      The objective of the study is to assess the efficacy, safety and PK of AZD8871 after a 14-day
      treatment period at 2 different doses in patients with moderate to severe COPD. The target
      population includes male and female (non-childbearing potential) adult patients with clinical
      diagnosis of moderate to severe COPD. The crossover design has been chosen to avoid
      inter-patient variability and optimize sample size. By randomly assigning treatment sequence,
      differences in baseline characteristics of the treatment groups will be minimised. The
      inclusion of a placebo arm is considered the most reliable method to minimise patient and
      Investigator bias. The proposed dose levels of AZD8871 in this study are 100 and 600 µg of
      AZD8871 given by inhalation once daily for 14 days through a single dose DPI. Doses have been
      selected based on the safety, tolerability, PK and pharmacodynamics (PD) information
      generated in previous clinical trials with AZD8871. The wash-out period proposed for this
      current study is a minimum of 28 days and up to 35 days in order to avoid any carry over
      effect between periods. The broad dose range selected (6 fold range from 100 to 600 µg) has
      been chosen to span the likely therapeutic dose and facilitate the dose selection for future
      studies. Considering the expected efficacy in patients with COPD and the available data to
      date, it is anticipated the benefits will outweigh the risks and support the continued
      investigation of AZD8871 in clinical studies.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)
time frame: On Day 15
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 15
measure: Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Single Dose)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.
description: Observed maximum concentration, taken directly from the individual concentration-time curve, on Day 1 of each treatment period.
measure: Observed Maximum Plasma (Cmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.
description: Observed maximum concentration, taken directly from the individual concentration-time curve, on Day 14 of each treatment period.
measure: Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Single Dose)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.
description: Time to reach maximum concentration taken directly from the individual concentration-time curve on Day 1 of each treatment period.
measure: Time to Reach Maximum Plasma Concentration (Tmax) of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.
description: Time to reach maximum concentration taken directly from the individual concentration-time curve on Day 14 of each treatment period.
measure: AUClast of AZD8871 and Its Metabolites (Single Dose)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.
description: Area under the plasma concentration-curve from time zero to the last quantifiable time point (24 hours post-dose) calculated on Day 1 of each treatment period.
measure: AUClast of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.
description: Area under the plasma concentration-curve from time zero to the last quantifiable time point (24 hours post-dose) calculated on Day 14 of each treatment period.
measure: AUC0-24 of AZD8871 and Its Metabolites (Single Dose)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1.
description: Area under the plasma concentration-curve from time zero to 24 hours post-dose calculated on Day 1 of each treatment period.
measure: AUC0-24 of AZD8871 and Its Metabolites (Multiple Doses, Day 14)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.
description: Area under the plasma concentration-curve from time zero to 24 hours post-dose calculated on Day 14 of each treatment period.
measure: Accumulation Ratio for Cmax (RacCmax) of AZD8871 and Its Metabolites (Day 14)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 14.
description: Accumulation ratio for Cmax estimated as (Cmax on Day 14 / Cmax on Day 1) in each treatment period.
measure: Accumulation Ratio for AUC0-24 (RacAUC[0-24]) of AZD8871 and Its Metabolites (Day 14)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 14.
description: Accumulation ratio for AUC0-24 estimated as AUC0-24 on Day 14 / AUC0-24 on Day 1 in each treatment period.
measure: Cavg of AZD8871 and Its Metabolites During a Dosing Interval (Day 14)
time frame: Pre-dose and 30 min, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Day 14.
description: Average plasma concentration during a dosing interval calculated on Day 14 of each treatment period.
measure: Change From Baseline in Trough FEV1 at Day 1 (Single Dose)
time frame: on Day 1
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 1
measure: Change From Baseline in Trough FEV1 at Day 8 (Pre-dose)
time frame: on Day 8 (pre-dose)
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 on Day 8 (pre-dose)
measure: Change From Baseline in Trough FEV1 Over the Treatment Duration (Days 1-15)
time frame: Days 1-15
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in trough FEV1 over the treatment duration from Day 1 to Day 15
measure: Change From Baseline in Peak FEV1 at Day 1 (Single Dose)
time frame: on Day 1
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1
measure: Change From Baseline in Peak FEV1 at Day 8
time frame: on Day 8
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1
measure: Change From Baseline in Peak FEV1 at Day 14
time frame: on Day 14
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1
measure: Change From Baseline in Peak FEV1 Over the Treatment Duration (Days 1-15)
time frame: over the treatment duration (Days 1-15)
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change in Peak FEV1
measure: Change From Baseline in BCSS Questionnaire Total Score From Day 1 to Day 8 Post-treatment
time frame: From Day 1 to Day 8 post-treatment
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change from baseline in Total score of the Breathlessness, Cough Sputum Scale (BCSS) questionnaire.
The BCSS questionnaire is a 3-item patient-reported outcome measure. On a daily basis, patients rated 3 symptoms (breathlessness, cough and sputum) on a 5-point Likert scale (range 0-4, high scores indicating higher severity). The BCSS questionnaire Total Score is the sum of the 3 symptom scores, ranging from 0-12 (lowest-highest severity).
measure: Change From Baseline in BCSS Questionnaire Total Score From Day 9 to Day 14 Post-treatment
time frame: From Day 9 to Day 14 post-treatment
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD was assessed by measuring the change from baseline in Total score of the Breathlessness, Cough Sputum Scale (BCSS) questionnaire.
The BCSS questionnaire is a 3-item patient-reported outcome measure. On a daily basis, patients rated 3 symptoms (breathlessness, cough and sputum) on a 5-point Likert scale (range 0-4, high scores indicating higher severity). The BCSS questionnaire Total Score is the sum of the 3 symptom scores, ranging from 0-12 (lowest-highest severity).
measure: Change From Baseline in Cough Individual Domain Score From Day 1 to Day 8 Post-treatment
time frame: From Day 1 to Day 8 post-treatment
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire cough individual domain scores.
On a daily basis, patients rated cough symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).
measure: Change From Baseline in Cough Individual Domain Score From Day 9 to Day 14 Post-treatment
time frame: From Day 9 to Day 14 post-treatment
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire cough individual domain scores.
On a daily basis, patients rated cough symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).
measure: Change From Baseline in Breathlessness Individual Domain Score From Day 1 to Day 8 Post-treatment
time frame: From Day 1 to Day 8 post-treatment
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire breathlessness individual domain scores.
On a daily basis, patients rated breathlessness symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).
measure: Change From Baseline in Breathlessness Individual Domain Score From Day 9 to Day 14 Post-treatment
time frame: From Day 9 to Day 14 post-treatment
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire breathlessness individual domain scores.
On a daily basis, patients rated breathlessness symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).
measure: Change From Baseline in Sputum Individual Domain Score From Day 1 to Day 8 Post-treatment
time frame: From Day 1 to Day 8 post-treatment
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire sputum individual domain scores.
On a daily basis, patients rated sputum symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).
measure: Change From Baseline in Sputum Individual Domain Score From Day 9 to Day 14 Post-treatment
time frame: From Day 9 to Day 14 post-treatment
description: The efficacy of inhaled AZD8871 in patients with moderate to severe COPD will be assessed by measuring the change from baseline in Breathlessness, Cough Sputum Scale (BCSS) questionnaire sputum individual domain scores.
On a daily basis, patients rated sputum symptoms on a 5-point Likert scale (range 0-4, high scores indicating higher severity).
arm group label: AZD8871 100 µg
arm group type: Experimental
description: The subjects will receive AZD8871 100 µg once daily, by dry powder inhaler (DPI) device. The treatment will be administered via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
arm group label: Placebo
arm group type: Placebo Comparator
description: The placebo will be administered via single dose DPI that is an adaptation of the commercially available Genuair® with a smaller internal volume to enable delivery of single doses. To maintain blinding, each patient will receive one inhaled dose from placebo DPI provided to him/her on each day of the treatment period.
arm group label: AZD8871 600 µg
arm group type: Experimental
description: The subjects will receive AZD8871 600 µg once daily by DPI device via single dose DPI that is an adaptation of the multi-dose Genuair™ used in approved inhalation products.
intervention type: Drug
intervention name: AZD8871 100 µg
description: The subjects will receive one dose of AZD8871 100 µg single dose DPI.
arm group label: AZD8871 100 µg
intervention type: Drug
intervention name: AZD8871 600 µg
description: The subjects will receive AZD8871, 600 µg single dose DPI.
arm group label: AZD8871 600 µg
intervention type: Drug
intervention name: Placebo
description: The subject will receive Placebo single dose DPI.
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Dave Singh, Prof
role: Principal Investigator
affiliation: Medicines Evaluation Unit, Manchester, United Kingdom
last name: Rainard Fuhr, Dr
role: Principal Investigator
affiliation: PAREXEL International GmbH EPCU Berlin
facility: 
facility: 
country: Germany
country: United Kingdom
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=4121&filename=AZD8871%20D6640C00006%20Clinical%20Study%20Protocol%20(CSP)_redacted.pdf
description: Related Info
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=4121&filename=azd8871-d6640c00004-redacted-sap-ed-1-3.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 