<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/NCT03250689</url>
  </required_header>
  <id_info>
    <org_study_id>207551</org_study_id>
    <secondary_id>2017-001069-25</secondary_id>
    <nct_id>NCT03250689</nct_id>
  </id_info>
  <brief_title>Randomized Study Evaluating the Effect of Danirixin on Neutrophil Extracellular Traps (NETs) in Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <official_title>Randomized Double Blind (Sponsor Unblind) Study Evaluating the Effect of 14 Days of Treatment With Danirixin (GSK1325756) on Neutrophil Extracellular Traps (NETs) Formation in Participants With Stable Chronic Obstructive Pulmonary Disease (COPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The inflammation associated with COPD is characterized by a prominent infiltration of&#xD;
      neutrophils in lung tissue and airways. The CXC chemokine receptor type 2 (CXCR2) plays a&#xD;
      pivotal role in neutrophil recruitment to the lungs resulting in progressive fibrosis, airway&#xD;
      stenosis, and destruction of the lung parenchyma characteristic of COPD. There is a paucity&#xD;
      of novel therapies that target these symptoms, and there are no currently available therapies&#xD;
      that modify disease progression in COPD. Danirixin (GSK1325756) is a selective CXCR2&#xD;
      antagonist being developed as a potential anti-inflammatory agent for the treatment of COPD&#xD;
      and influenza. This study is a mechanistic study which aims to evaluate the effect of&#xD;
      danirixin in reducing neutrophil extracellular traps (NETs) formation (or NETosis). Subjects&#xD;
      will be randomized (3:1) to receive danirixin hydrobromide (HBr) 35 milligram (mg) orally&#xD;
      twice daily or matching placebo for 14 days. Subjects may continue to use rescue&#xD;
      medication(s) and inhaled COPD maintenance medication(s) during the study. The study will&#xD;
      consist of a screening period of up to 30 days, a 2 week treatment period, and a 1-week&#xD;
      follow-up visit via phone call. Approximately 50 subjects will be screened to obtain&#xD;
      approximately 24 subjects to complete the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated due to a change in the benefit-risk profile for danirixin in COPD.&#xD;
  </why_stopped>
  <start_date type="Actual">November 15, 2017</start_date>
  <completion_date type="Actual">October 8, 2018</completion_date>
  <primary_completion_date type="Actual">October 8, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage Change From Baseline in Sputum Neutrophil Extracellular Traps (NETs) Quantified by Histone-Elastase Complexes</measure>
    <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
    <description>Sputum samples were collected at indicated time points to assess NET formation via histone elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value. Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by 100. Analysis was performed using a mixed effect repeated measures model with covariates of treatment group, log(Baseline NETs) and treatment group by day interaction. The response variable was the log of the ratio of post-Baseline NETs to Baseline NETs. Primary completer population consisted of all participants in the Modified Intent-To-Treat population who had completed the assessments supporting the primary endpoint (sputum NETs).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Sputum NETs Quantified by Deoxyribonucleic Acid (DNA)-Elastase Complexes</measure>
    <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
    <description>Sputum samples were collected at indicated time points to assess NET formation via DNA elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Percentage of Microscope Field Area Occupied by Sputum NETs</measure>
    <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
    <description>Sputum samples were collected at indicated time points and NETs area was quantified by microscopy. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Up to Day 21</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes, Modified Intent-to-Treat Population consisted of all randomized participants who received at least one dose of study treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)</measure>
    <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
    <description>SBP and DBP were measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Heart Rate</measure>
    <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
    <description>Heart rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Respiration Rate</measure>
    <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
    <description>Respiration rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in PR Interval, QRS Duration, QT Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF)</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Triplicate 12-lead electrocardiograms (ECG) were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry: Forced Expiratory Volume in One Second (FEV1) at Indicated Time Points</measure>
    <time_frame>Day 1 and Day 14</time_frame>
    <description>FEV1 is the amount of air that can be forcefully exhaled from the lungs in the first second of a forced exhalation. It was measured by spirometry test. Mean and standard deviation data of FEV1 measured at Day 1 and Day 14 have been presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry: Forced Vital Capacity (FVC) at Indicated Time Points</measure>
    <time_frame>Day 1 and Day 14</time_frame>
    <description>FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. Mean and standard deviation data of FVC measured at Day 1 and Day 14 have been presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Counts, Total Neutrophils, White Blood Cell (WBC) Count</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets counts, Total neutrophils and WBC count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Hematocrit</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Hemoglobin</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Mean Corpuscular Volume</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Volume. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematology Parameter: Red Blood Cell Count</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected to analyze the hematology parameter: Red Blood Cell count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Urea</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected to analyze the chemistry parameters: Calcium, Glucose, Potassium, Sodium and Urea. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Chemistry Parameters: Creatinine, Direct Bilirubin, Total Bilirubin</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected to analyze the chemistry parameters: Creatinine, Direct Bilirubin and Total Bilirubin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Urinalysis Parameter: Specific Gravity</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Urinary specific gravity measurement is a part of routine urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Sputum Resistin Levels</measure>
    <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
    <description>Sputum samples were collected at indicated time points to analyze resistin levels. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Ratio of Sputum NETs to Sputum Neutrophils</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Sputum samples were collected to calculate ratio of sputum NETs to sputum neutrophils. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value. The ratio is calculated as the sputum NETs divided by the number of sputum neutrophils.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Sputum Elastase Activity</measure>
    <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
    <description>Sputum samples were collected at indicated time points to analyze sputum elastase activity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by DNA Release</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by DNA release. DNA-elastase complexes quantified NETs formation. Phorbol 12-myristate 13-acetate (PMA) was used to induce inflammation and NETs formation in the PMA stimulated samples. Blood from participants were tested at Baseline and Day 14 for non-PMA stimulated samples, and at Baseline and Day 14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally (non PMA induced) or where NETs formation was already raised (PMA stimulated). Hence participants were counted in both the categories - PMA stimulated and not PMA stimulated. NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by Microscopy</measure>
    <time_frame>Baseline (Day 1) and Day 14</time_frame>
    <description>Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by microscopy.DNA-elastase complexes quantified NETs formation.PMA was used to induce inflammation and NETs formation in PMA stimulated samples. Blood from participants were tested at Baseline and Day14 for non-PMA stimulated samples,and at Baseline and Day14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally(non PMA induced)or where NETs formation was already raised(PMA stimulated).Participants were counted in both categories-PMA stimulated and not PMA stimulated.NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA.Baseline was considered as Day1.Change from Baseline was calculated as post-Baseline value minus Baseline value.Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Concentration (Cmax) of Danirixin</measure>
    <time_frame>Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose</time_frame>
    <description>Blood samples were collected to evaluate the pharmacokinetic (PK) of danirixin at the indicated time points for the analysis of Cmax. PK population consisted of all participants in the Modified Intent-To-Treat population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Cmax (Tmax) of Danirixin</measure>
    <time_frame>Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose</time_frame>
    <description>Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Blood Concentration-time Curve [AUC(0-t)] of Danirixin</measure>
    <time_frame>Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose</time_frame>
    <description>Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of AUC(0-t).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of Last Observed Concentration (Tlast) of Danirixin</measure>
    <time_frame>Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose</time_frame>
    <description>Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tlast.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>Danirixin 35 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible subjects will receive danirixin 35 mg tablet with food twice daily for 14 Days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Comparator</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible subjects will receive placebo tablet with food twice daily for 14 Days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Danirixin</intervention_name>
    <description>Danirixin will be available as 35 mg oval shaped, white film coated HBr embossed tablets.</description>
    <arm_group_label>Danirixin 35 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo will be available as oval shaped, white film coated tablets.</description>
    <arm_group_label>Placebo Comparator</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rescue medication</intervention_name>
    <description>Subjects may continue to use rescue medication(s) anytime during the study. The following rescue medications may be used: short acting beta agonists, short acting muscarinic antagonists, or short acting combination bronchodilators.</description>
    <arm_group_label>Danirixin 35 mg</arm_group_label>
    <arm_group_label>Placebo Comparator</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inhaled COPD maintenance medication</intervention_name>
    <description>Subjects may continue to use inhaled COPD maintenance medication(s) during the study, at the discretion of the GSK Medical Monitor and/or Investigator. The following maintenance medications may be used: long acting bronchodilator medications (e.g. long-acting muscarinic antagonist [LAMA], long-acting beta-agonist [LABA]) and long-acting bronchodilator combination therapies (e.g. LAMA/LABA) and long-acting bronchodilator/inhaled corticosteroid steroid combination (ICS) therapies (e.g. LABA/ICS, LAMA/LABA/ICS)</description>
    <arm_group_label>Danirixin 35 mg</arm_group_label>
    <arm_group_label>Placebo Comparator</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject must be 50 to 75 years of age inclusive, at the time of signing the informed&#xD;
             consent.&#xD;
&#xD;
          -  Diagnosis of COPD with mild to moderate airflow obstruction FEV1/FVC ratio &lt;0.7 and&#xD;
             FEV1% predicted (pred) &gt;=40% at screening) based on the Quanjer reference equations,&#xD;
             with spirometry conducted according to American Thoracic Society (ATS)/European&#xD;
             Respiratory Society (ERS) current guidelines.&#xD;
&#xD;
          -  Elevated sputum neutrophil extracellular traps based on screening assay for&#xD;
             histone-elastase complexes of &gt;0.5 units/ milliliter (mL) sputum. Two further&#xD;
             screening samples can be submitted for analysis within 30 day screening period if&#xD;
             previous samples do not pass criteria.&#xD;
&#xD;
          -  Able to produce at least 1 mL of sputum sample at the screening visit with nebulized&#xD;
             saline induction.&#xD;
&#xD;
          -  Current smokers and former smokers with a cigarette smoking history of &gt;=10 pack years&#xD;
             (1 pack year=20 cigarettes smoked per day for 1 year or equivalent). Former smokers&#xD;
             are defined as those who have stopped smoking for at least 6 months prior to Visit 1.&#xD;
&#xD;
          -  Body weight &gt;=45 kilogram (kg).&#xD;
&#xD;
          -  Male or female.&#xD;
&#xD;
          -  A male subject must agree to use contraception during the treatment period and for at&#xD;
             least [60 hours, corresponding to approximately 6 half-lives (which is the time needed&#xD;
             to eliminate any teratogenic treatments after the last dose of study treatment and&#xD;
             refrain from donating sperm during this period.&#xD;
&#xD;
          -  A female subject is eligible to participate if she is not pregnant, not breastfeeding,&#xD;
             and is not a woman of childbearing potential (WOCBP) OR a WOCBP who agrees to follow&#xD;
             the contraceptive guidance during the treatment period and for at least 60 hours after&#xD;
             the last dose of study treatment.&#xD;
&#xD;
          -  Capable of giving signed informed consent which includes compliance with the&#xD;
             requirements and restrictions listed in the informed consent form (ICF) and in this&#xD;
             protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Primary clinical diagnoses of any of the following relevant lung diseases; asthma,&#xD;
             sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis or lung cancer.&#xD;
&#xD;
          -  Known alpha-1-antitrypsin deficiency.&#xD;
&#xD;
          -  Pulse oximetry &lt;88% at rest at screening. Subjects should be tested while breathing&#xD;
             room air.&#xD;
&#xD;
          -  Subjects on long term oxygen therapy (defined as &gt;15 hours/day of oxygen use).&#xD;
&#xD;
          -  Unstable co-morbidities (e.g. cardiovascular disease, active malignancy) which in the&#xD;
             opinion of the Investigator would make the subject unsuitable to be enrolled in the&#xD;
             study. This includes any abnormality identified on screening bloods or screening ECG&#xD;
             which in the opinion of the Investigator would make the subject unsuitable for the&#xD;
             study.&#xD;
&#xD;
          -  History of sensitivity to any of the study medications, or components thereof or a&#xD;
             history of drug or other allergy that, in the opinion of the investigator of GSK&#xD;
             medical monitor, contraindicates their participation.&#xD;
&#xD;
          -  Current or chronic history of liver disease, or know hepatic or biliary abnormalities&#xD;
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).&#xD;
&#xD;
          -  Subjects with a known or suspected history of alcohol or drug abuse within the last 2&#xD;
             years.&#xD;
&#xD;
          -  Antibiotic use concurrently or within 28 days preceding the screening visit, including&#xD;
             current or planned chronic use of macrolide antibiotics during the study period for&#xD;
             the prevention of COPD exacerbations. Examples of chronic use include daily or&#xD;
             two-three times per week for at least 3 months.&#xD;
&#xD;
          -  Systemic immunosuppressive medication, including current oral corticosteroids at a&#xD;
             dose &gt;5 milligram (mg), concurrently or within 28 days preceding the screening visit.&#xD;
&#xD;
          -  Oral or injectable Cytochrome P450 (CYP) 3A4 or Breast Cancer Resistance Protein&#xD;
             (BCRP) substrates with narrow therapeutic index (CYP3A4 substrates include, but are&#xD;
             not limited to, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl,&#xD;
             pimozide, quinidine, sirolimus, tacrolimus, and theophylline; BCRP substrates include:&#xD;
             Methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin,&#xD;
             sulfasalazine, topotecan.&#xD;
&#xD;
          -  Current use of phosphodiesterase-4 inhibitors: Roflumilast, Crisaborole and&#xD;
             Apremilast.&#xD;
&#xD;
          -  Current use of Raloxifene.&#xD;
&#xD;
          -  Current use of low molecular weight heparin.&#xD;
&#xD;
          -  The subject has participated in a clinical trial and has received an investigational&#xD;
             product within the following time period prior to the first dosing day in the current&#xD;
             study: 30 days, 5 half lives, or twice the duration of the biological effect of the&#xD;
             investigational product (whichever is longer).&#xD;
&#xD;
          -  Exposure to more than four investigational products within 12 months prior to the&#xD;
             first dosing day.&#xD;
&#xD;
          -  Subjects with a peripheral blood neutrophil count &lt; 1.0x10^9/liter (L) at screening.&#xD;
&#xD;
          -  Diagnosis of pneumonia (chest X-ray or computed tomography [CT] confirmed) within the&#xD;
             3 months prior to screening.&#xD;
&#xD;
          -  Chest X-ray (posterior with lateral) or CT scan reveals evidence of a clinically&#xD;
             significant abnormality not believed to be due to the presence of COPD (historic data&#xD;
             up to 1 year may be used).&#xD;
&#xD;
          -  Abnormal and clinically significant 12-lead ECG finding at screening. The investigator&#xD;
             will determine the clinical significance of each abnormal ECG finding in relation to&#xD;
             the subject's medical history and exclude subjects who would be at undue risk by&#xD;
             participating in the trial. An abnormal and clinically significant finding that would&#xD;
             preclude a subject from entering the trial is defined as a 12-lead tracing that is&#xD;
             interpreted as, but not limited to, any of the following:&#xD;
&#xD;
          -  AF with rapid ventricular rate &gt; 120 beats per minute (bpm);&#xD;
&#xD;
          -  Sustained or non-sustained ventricular tachycardia (VT);&#xD;
&#xD;
          -  Second degree heart block Mobitz type II and third degree heart block (unless&#xD;
             pacemaker or defibrillator has been implanted);&#xD;
&#xD;
          -  QT interval corrected for heart rate by Fridericia's formula (QTcF) &gt;=500 millisecond&#xD;
             (msec) in subjects with QRS &lt;120 msec and QTcF &gt;=530 msec in subjects with QRS &gt;=120&#xD;
             msec.&#xD;
&#xD;
          -  Affiliation with a study site: study investigators, sub-investigators, study&#xD;
             coordinators, employees of a study investigator, sub-investigator or study site, or&#xD;
             immediate family members of any of the above that is involved with the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Dundee</city>
        <zip>DD1 9SY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Keir HR, Richardson H, Fillmore C, Shoemark A, Lazaar AL, Miller BE, Tal-Singer R, Chalmers JD, Mohan D. CXCL-8-dependent and -independent neutrophil activation in COPD: experiences from a pilot study of the CXCR2 antagonist danirixin. ERJ Open Res. 2020 Nov 10;6(4):00583-2020. doi: 10.1183/23120541.00583-2020. eCollection 2020 Oct.</citation>
    <PMID>33263062</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <results_first_submitted>August 29, 2019</results_first_submitted>
  <results_first_submitted_qc>October 17, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 8, 2019</results_first_posted>
  <last_update_submitted>February 26, 2021</last_update_submitted>
  <last_update_submitted_qc>February 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Danirixin</keyword>
  <keyword>CXCR2</keyword>
  <keyword>NETs</keyword>
  <keyword>GSK1325756</keyword>
  <keyword>COPD</keyword>
  <keyword>HBr</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD for this study is available via the Clinical Study Data Request site.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)</ipd_time_frame>
    <ipd_access_criteria>Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.</ipd_access_criteria>
    <ipd_url>https://clinicalstudydatarequest.com/Posting.aspx?ID=20764</ipd_url>
  </patient_data>
  <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>May 16, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT03250689/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>November 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT03250689/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at single center in United Kingdom. This study was terminated early due to a change in the benefit risk profile of danirixin observed in another study NCT03034967, leading to cessation of the overall danirixin development program.</recruitment_details>
      <pre_assignment_details>A total of 43 participants were screened, of which 23 were screen failures (23 participants did not meet inclusion/exclusion criteria). From the 20 participants who passed screening, 1 was not randomized due to study being terminated early. Hence, 19 participants were enrolled and received treatment in this study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
        </group>
        <group group_id="P2">
          <title>Danirixin Hydrobromide 35 mg</title>
          <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 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="5"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
        </group>
        <group group_id="B2">
          <title>Danirixin Hydrobromide 35 mg</title>
          <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="19"/>
          </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="61.6" spread="6.02"/>
                    <measurement group_id="B2" value="65.3" spread="7.03"/>
                    <measurement group_id="B3" value="64.3" spread="6.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>White: White/Caucasian/European Heritage</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage Change From Baseline in Sputum Neutrophil Extracellular Traps (NETs) Quantified by Histone-Elastase Complexes</title>
        <description>Sputum samples were collected at indicated time points to assess NET formation via histone elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value. Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by 100. Analysis was performed using a mixed effect repeated measures model with covariates of treatment group, log(Baseline NETs) and treatment group by day interaction. The response variable was the log of the ratio of post-Baseline NETs to Baseline NETs. Primary completer population consisted of all participants in the Modified Intent-To-Treat population who had completed the assessments supporting the primary endpoint (sputum NETs).</description>
        <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
        <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline in Sputum Neutrophil Extracellular Traps (NETs) Quantified by Histone-Elastase Complexes</title>
          <description>Sputum samples were collected at indicated time points to assess NET formation via histone elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value. Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by 100. Analysis was performed using a mixed effect repeated measures model with covariates of treatment group, log(Baseline NETs) and treatment group by day interaction. The response variable was the log of the ratio of post-Baseline NETs to Baseline NETs. Primary completer population consisted of all participants in the Modified Intent-To-Treat population who had completed the assessments supporting the primary endpoint (sputum NETs).</description>
          <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
          <units>Percent change</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7, n=3,6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.2" lower_limit="-77.0" upper_limit="306.6"/>
                    <measurement group_id="O2" value="-9.4" lower_limit="-64.4" upper_limit="130.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14, n=3,8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-30.5" lower_limit="-71.7" upper_limit="70.7"/>
                    <measurement group_id="O2" value="-13.6" lower_limit="-49.1" upper_limit="46.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Sputum NETs Quantified by Deoxyribonucleic Acid (DNA)-Elastase Complexes</title>
        <description>Sputum samples were collected at indicated time points to assess NET formation via DNA elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
        <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Sputum NETs Quantified by Deoxyribonucleic Acid (DNA)-Elastase Complexes</title>
          <description>Sputum samples were collected at indicated time points to assess NET formation via DNA elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
          <units>Units per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7, n=3,6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.83" spread="4.610"/>
                    <measurement group_id="O2" value="0.63" spread="1.859"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14, n=3,8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.53" spread="2.696"/>
                    <measurement group_id="O2" value="2.08" spread="4.072"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Percentage of Microscope Field Area Occupied by Sputum NETs</title>
        <description>Sputum samples were collected at indicated time points and NETs area was quantified by microscopy. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
        <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Percentage of Microscope Field Area Occupied by Sputum NETs</title>
          <description>Sputum samples were collected at indicated time points and NETs area was quantified by microscopy. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Percentage of microscope field area</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Data was not collected because 7 days treatment was insufficient to observe the changes in the sputum NETs via microscopy.</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Data was not collected because 7 days treatment was insufficient to observe the changes in the sputum NETs via microscopy.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.900" spread="0.9200"/>
                    <measurement group_id="O2" value="-0.259" spread="0.5183"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
        <description>An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes, Modified Intent-to-Treat Population consisted of all randomized participants who received at least one dose of study treatment.</description>
        <time_frame>Up to Day 21</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
          <description>An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes, Modified Intent-to-Treat Population consisted of all randomized participants who received at least one dose of study treatment.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)</title>
        <description>SBP and DBP were measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)</title>
          <description>SBP and DBP were measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Millimeters of mercury</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SBP, Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.2" spread="17.01"/>
                    <measurement group_id="O2" value="-4.1" spread="17.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP, Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4" spread="16.10"/>
                    <measurement group_id="O2" value="-5.3" spread="15.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.2" spread="9.91"/>
                    <measurement group_id="O2" value="-2.1" spread="10.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP, Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" spread="11.01"/>
                    <measurement group_id="O2" value="-5.3" spread="7.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Heart Rate</title>
        <description>Heart rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Heart Rate</title>
          <description>Heart rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" spread="6.02"/>
                    <measurement group_id="O2" value="1.6" spread="11.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" spread="6.89"/>
                    <measurement group_id="O2" value="0.1" spread="6.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Respiration Rate</title>
        <description>Respiration rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Respiration Rate</title>
          <description>Respiration rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Breaths per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="1.95"/>
                    <measurement group_id="O2" value="1.8" spread="2.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="0.84"/>
                    <measurement group_id="O2" value="2.1" spread="3.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in PR Interval, QRS Duration, QT Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF)</title>
        <description>Triplicate 12-lead electrocardiograms (ECG) were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in PR Interval, QRS Duration, QT Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF)</title>
          <description>Triplicate 12-lead electrocardiograms (ECG) were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PR Interval</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.6" spread="20.44"/>
                    <measurement group_id="O2" value="-4.8" spread="15.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QRS Duration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="1.12"/>
                    <measurement group_id="O2" value="0.5" spread="5.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QT Interval</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.8" spread="10.05"/>
                    <measurement group_id="O2" value="3.7" spread="15.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QTcF Interval</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.6" spread="0.38"/>
                    <measurement group_id="O2" value="-1.6" spread="5.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Spirometry: Forced Expiratory Volume in One Second (FEV1) at Indicated Time Points</title>
        <description>FEV1 is the amount of air that can be forcefully exhaled from the lungs in the first second of a forced exhalation. It was measured by spirometry test. Mean and standard deviation data of FEV1 measured at Day 1 and Day 14 have been presented.</description>
        <time_frame>Day 1 and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Spirometry: Forced Expiratory Volume in One Second (FEV1) at Indicated Time Points</title>
          <description>FEV1 is the amount of air that can be forcefully exhaled from the lungs in the first second of a forced exhalation. It was measured by spirometry test. Mean and standard deviation data of FEV1 measured at Day 1 and Day 14 have been presented.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.458" spread="0.6331"/>
                    <measurement group_id="O2" value="1.914" spread="0.7267"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.344" spread="0.7174"/>
                    <measurement group_id="O2" value="1.910" spread="0.7428"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Spirometry: Forced Vital Capacity (FVC) at Indicated Time Points</title>
        <description>FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. Mean and standard deviation data of FVC measured at Day 1 and Day 14 have been presented.</description>
        <time_frame>Day 1 and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Spirometry: Forced Vital Capacity (FVC) at Indicated Time Points</title>
          <description>FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. Mean and standard deviation data of FVC measured at Day 1 and Day 14 have been presented.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.026" spread="1.2021"/>
                    <measurement group_id="O2" value="3.416" spread="1.1304"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.036" spread="1.3992"/>
                    <measurement group_id="O2" value="3.369" spread="1.1456"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Counts, Total Neutrophils, White Blood Cell (WBC) Count</title>
        <description>Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets counts, Total neutrophils and WBC count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Counts, Total Neutrophils, White Blood Cell (WBC) Count</title>
          <description>Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets counts, Total neutrophils and WBC count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Giga cells per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Basophils</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.000"/>
                    <measurement group_id="O2" value="-0.02" spread="0.058"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eosinophils</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.040" spread="0.0686"/>
                    <measurement group_id="O2" value="-0.020" spread="0.0609"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.20" spread="0.316"/>
                    <measurement group_id="O2" value="-0.08" spread="0.269"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monocytes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" spread="0.114"/>
                    <measurement group_id="O2" value="0.02" spread="0.080"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets counts</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.2" spread="18.94"/>
                    <measurement group_id="O2" value="-7.9" spread="41.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total neutrophils</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.38" spread="0.965"/>
                    <measurement group_id="O2" value="0.29" spread="0.943"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>WBC count</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.56" spread="0.948"/>
                    <measurement group_id="O2" value="0.16" spread="1.075"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Hematocrit</title>
        <description>Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Hematocrit</title>
          <description>Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Percentage of red blood cells in blood</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0058" spread="0.02279"/>
                    <measurement group_id="O2" value="-0.0115" spread="0.02085"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Hemoglobin</title>
        <description>Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Hemoglobin</title>
          <description>Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Grams per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.2" spread="6.72"/>
                    <measurement group_id="O2" value="-5.4" spread="7.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Mean Corpuscular Volume</title>
        <description>Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Volume. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Mean Corpuscular Volume</title>
          <description>Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Volume. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Femtoliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" spread="1.339"/>
                    <measurement group_id="O2" value="0.31" spread="1.263"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin</title>
        <description>Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin</title>
          <description>Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Picograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.08" spread="0.920"/>
                    <measurement group_id="O2" value="-0.22" spread="0.749"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematology Parameter: Red Blood Cell Count</title>
        <description>Blood samples were collected to analyze the hematology parameter: Red Blood Cell count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematology Parameter: Red Blood Cell Count</title>
          <description>Blood samples were collected to analyze the hematology parameter: Red Blood Cell count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Trillion cells per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.070" spread="0.2081"/>
                    <measurement group_id="O2" value="-0.154" spread="0.2171"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)</title>
        <description>Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)</title>
          <description>Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>International units per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ALT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" spread="4.39"/>
                    <measurement group_id="O2" value="-1.9" spread="8.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALP</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="6.26"/>
                    <measurement group_id="O2" value="1.3" spread="13.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="2.61"/>
                    <measurement group_id="O2" value="-3.1" spread="2.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Urea</title>
        <description>Blood samples were collected to analyze the chemistry parameters: Calcium, Glucose, Potassium, Sodium and Urea. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Urea</title>
          <description>Blood samples were collected to analyze the chemistry parameters: Calcium, Glucose, Potassium, Sodium and Urea. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Millimoles per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Calcium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.032" spread="0.0782"/>
                    <measurement group_id="O2" value="-0.034" spread="0.0947"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.36" spread="0.635"/>
                    <measurement group_id="O2" value="0.12" spread="0.398"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.12" spread="0.148"/>
                    <measurement group_id="O2" value="0.06" spread="0.287"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="1.58"/>
                    <measurement group_id="O2" value="0.2" spread="2.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.42" spread="0.867"/>
                    <measurement group_id="O2" value="0.26" spread="0.777"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Chemistry Parameters: Creatinine, Direct Bilirubin, Total Bilirubin</title>
        <description>Blood samples were collected to analyze the chemistry parameters: Creatinine, Direct Bilirubin and Total Bilirubin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Chemistry Parameters: Creatinine, Direct Bilirubin, Total Bilirubin</title>
          <description>Blood samples were collected to analyze the chemistry parameters: Creatinine, Direct Bilirubin and Total Bilirubin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Micromoles per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Creatinine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" spread="5.86"/>
                    <measurement group_id="O2" value="1.2" spread="6.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct Bilirubin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="0.55"/>
                    <measurement group_id="O2" value="0.7" spread="1.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Bilirubin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="0.84"/>
                    <measurement group_id="O2" value="-1.2" spread="3.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Urinalysis Parameter: Specific Gravity</title>
        <description>Urinary specific gravity measurement is a part of routine urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Urinalysis Parameter: Specific Gravity</title>
          <description>Urinary specific gravity measurement is a part of routine urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>Unitless</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0030" spread="0.00908"/>
                    <measurement group_id="O2" value="0.0046" spread="0.00887"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)</title>
        <description>Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)</title>
          <description>Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population.</population>
          <units>pH</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" spread="1.225"/>
                    <measurement group_id="O2" value="-0.25" spread="0.672"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Sputum Resistin Levels</title>
        <description>Sputum samples were collected at indicated time points to analyze resistin levels. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
        <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Sputum Resistin Levels</title>
          <description>Sputum samples were collected at indicated time points to analyze resistin levels. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
          <units>Nanograms per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7, n=3,6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.93" spread="15.513"/>
                    <measurement group_id="O2" value="-2.01" spread="4.629"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14, n=3,8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.28" spread="27.619"/>
                    <measurement group_id="O2" value="2.61" spread="2.711"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Ratio of Sputum NETs to Sputum Neutrophils</title>
        <description>Sputum samples were collected to calculate ratio of sputum NETs to sputum neutrophils. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value. The ratio is calculated as the sputum NETs divided by the number of sputum neutrophils.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Ratio of Sputum NETs to Sputum Neutrophils</title>
          <description>Sputum samples were collected to calculate ratio of sputum NETs to sputum neutrophils. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value. The ratio is calculated as the sputum NETs divided by the number of sputum neutrophils.</description>
          <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5200" spread="0.41000"/>
                    <measurement group_id="O2" value="0.4557" spread="0.53149"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Sputum Elastase Activity</title>
        <description>Sputum samples were collected at indicated time points to analyze sputum elastase activity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1), Day 7 and Day 14</time_frame>
        <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Sputum Elastase Activity</title>
          <description>Sputum samples were collected at indicated time points to analyze sputum elastase activity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
          <units>Nanograms per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7, n=3,6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="638.0" spread="381.36"/>
                    <measurement group_id="O2" value="238.0" spread="224.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14, n=3,8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="411.3" spread="439.20"/>
                    <measurement group_id="O2" value="66.1" spread="45.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by DNA Release</title>
        <description>Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by DNA release. DNA-elastase complexes quantified NETs formation. Phorbol 12-myristate 13-acetate (PMA) was used to induce inflammation and NETs formation in the PMA stimulated samples. Blood from participants were tested at Baseline and Day 14 for non-PMA stimulated samples, and at Baseline and Day 14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally (non PMA induced) or where NETs formation was already raised (PMA stimulated). Hence participants were counted in both the categories - PMA stimulated and not PMA stimulated. NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by DNA Release</title>
          <description>Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by DNA release. DNA-elastase complexes quantified NETs formation. Phorbol 12-myristate 13-acetate (PMA) was used to induce inflammation and NETs formation in the PMA stimulated samples. Blood from participants were tested at Baseline and Day 14 for non-PMA stimulated samples, and at Baseline and Day 14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally (non PMA induced) or where NETs formation was already raised (PMA stimulated). Hence participants were counted in both the categories - PMA stimulated and not PMA stimulated. NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.</description>
          <population>Modified Intent-to-Treat Population. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Relative fluorescence units</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Not PMA stimulated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3044.8" spread="4251.78"/>
                    <measurement group_id="O2" value="-721.1" spread="731.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PMA stimulated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-96.8" spread="9418.43"/>
                    <measurement group_id="O2" value="-1211.0" spread="5102.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by Microscopy</title>
        <description>Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by microscopy.DNA-elastase complexes quantified NETs formation.PMA was used to induce inflammation and NETs formation in PMA stimulated samples. Blood from participants were tested at Baseline and Day14 for non-PMA stimulated samples,and at Baseline and Day14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally(non PMA induced)or where NETs formation was already raised(PMA stimulated).Participants were counted in both categories-PMA stimulated and not PMA stimulated.NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA.Baseline was considered as Day1.Change from Baseline was calculated as post-Baseline value minus Baseline value.Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by100.</description>
        <time_frame>Baseline (Day 1) and Day 14</time_frame>
        <population>Modified Intent-to-Treat Population. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by Microscopy</title>
          <description>Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by microscopy.DNA-elastase complexes quantified NETs formation.PMA was used to induce inflammation and NETs formation in PMA stimulated samples. Blood from participants were tested at Baseline and Day14 for non-PMA stimulated samples,and at Baseline and Day14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally(non PMA induced)or where NETs formation was already raised(PMA stimulated).Participants were counted in both categories-PMA stimulated and not PMA stimulated.NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA.Baseline was considered as Day1.Change from Baseline was calculated as post-Baseline value minus Baseline value.Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by100.</description>
          <population>Modified Intent-to-Treat Population. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Percent change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Not PMA stimulated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="927.5" spread="585.03"/>
                    <measurement group_id="O2" value="560.5" spread="395.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PMA stimulated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.7" spread="41.79"/>
                    <measurement group_id="O2" value="90.6" spread="60.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Concentration (Cmax) of Danirixin</title>
        <description>Blood samples were collected to evaluate the pharmacokinetic (PK) of danirixin at the indicated time points for the analysis of Cmax. PK population consisted of all participants in the Modified Intent-To-Treat population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values).</description>
        <time_frame>Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose</time_frame>
        <population>PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Concentration (Cmax) of Danirixin</title>
          <description>Blood samples were collected to evaluate the pharmacokinetic (PK) of danirixin at the indicated time points for the analysis of Cmax. PK population consisted of all participants in the Modified Intent-To-Treat population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values).</description>
          <population>PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
          <units>Nanograms per milliliter</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="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1, n=14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="855.2" spread="52.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14, n=13</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1135.2" spread="65.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Cmax (Tmax) of Danirixin</title>
        <description>Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tmax.</description>
        <time_frame>Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose</time_frame>
        <population>PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Cmax (Tmax) of Danirixin</title>
          <description>Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tmax.</description>
          <population>PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1, n=14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.000" lower_limit="0.50" upper_limit="4.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14, n=13</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.000" lower_limit="0.50" upper_limit="4.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Blood Concentration-time Curve [AUC(0-t)] of Danirixin</title>
        <description>Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of AUC(0-t).</description>
        <time_frame>Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose</time_frame>
        <population>PK Population. Only those participants with data available at the specified data points were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Blood Concentration-time Curve [AUC(0-t)] of Danirixin</title>
          <description>Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of AUC(0-t).</description>
          <population>PK Population. Only those participants with data available at the specified data points were analyzed.</population>
          <units>Hours * nanograms per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2173.4" spread="39.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2751.1" spread="51.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time of Last Observed Concentration (Tlast) of Danirixin</title>
        <description>Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tlast.</description>
        <time_frame>Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose</time_frame>
        <population>PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
        <group_list>
          <group group_id="O1">
            <title>Danirixin Hydrobromide 35 mg</title>
            <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Time of Last Observed Concentration (Tlast) of Danirixin</title>
          <description>Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tlast.</description>
          <population>PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1, n=14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.000" lower_limit="4.00" upper_limit="4.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14, n=13</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.000" lower_limit="4.00" upper_limit="4.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs and SAEs were collected from start of the treatment up to Day 21</time_frame>
      <desc>AEs and SAEs were collected for modified Intent-to-Treat Population which consisted of all randomized participants who received at least one dose of study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received one tablet of matching placebo twice daily orally with food for 14 days.</description>
        </group>
        <group group_id="E2">
          <title>Danirixin Hydrobromide 35 mg</title>
          <description>Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.1</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="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural complication</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Sputum increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</phone>
      <email>GSKClinicalSupportHD@gsk.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/NCT03250689
org study id: 207551
secondary id: 2017-001069-25
nct id: NCT03250689
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The inflammation associated with COPD is characterized by a prominent infiltration of
      neutrophils in lung tissue and airways. The CXC chemokine receptor type 2 (CXCR2) plays a
      pivotal role in neutrophil recruitment to the lungs resulting in progressive fibrosis, airway
      stenosis, and destruction of the lung parenchyma characteristic of COPD. There is a paucity
      of novel therapies that target these symptoms, and there are no currently available therapies
      that modify disease progression in COPD. Danirixin (GSK1325756) is a selective CXCR2
      antagonist being developed as a potential anti-inflammatory agent for the treatment of COPD
      and influenza. This study is a mechanistic study which aims to evaluate the effect of
      danirixin in reducing neutrophil extracellular traps (NETs) formation (or NETosis). Subjects
      will be randomized (3:1) to receive danirixin hydrobromide (HBr) 35 milligram (mg) orally
      twice daily or matching placebo for 14 days. Subjects may continue to use rescue
      medication(s) and inhaled COPD maintenance medication(s) during the study. The study will
      consist of a screening period of up to 30 days, a 2 week treatment period, and a 1-week
      follow-up visit via phone call. Approximately 50 subjects will be screened to obtain
      approximately 24 subjects to complete the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage Change From Baseline in Sputum Neutrophil Extracellular Traps (NETs) Quantified by Histone-Elastase Complexes
time frame: Baseline (Day 1), Day 7 and Day 14
description: Sputum samples were collected at indicated time points to assess NET formation via histone elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value. Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by 100. Analysis was performed using a mixed effect repeated measures model with covariates of treatment group, log(Baseline NETs) and treatment group by day interaction. The response variable was the log of the ratio of post-Baseline NETs to Baseline NETs. Primary completer population consisted of all participants in the Modified Intent-To-Treat population who had completed the assessments supporting the primary endpoint (sputum NETs).
measure: Change From Baseline in Sputum NETs Quantified by Deoxyribonucleic Acid (DNA)-Elastase Complexes
time frame: Baseline (Day 1), Day 7 and Day 14
description: Sputum samples were collected at indicated time points to assess NET formation via DNA elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Percentage of Microscope Field Area Occupied by Sputum NETs
time frame: Baseline (Day 1), Day 7 and Day 14
description: Sputum samples were collected at indicated time points and NETs area was quantified by microscopy. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Up to Day 21
description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes, Modified Intent-to-Treat Population consisted of all randomized participants who received at least one dose of study treatment.
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
time frame: Baseline (Day 1), Day 7 and Day 14
description: SBP and DBP were measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Heart Rate
time frame: Baseline (Day 1), Day 7 and Day 14
description: Heart rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Respiration Rate
time frame: Baseline (Day 1), Day 7 and Day 14
description: Respiration rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in PR Interval, QRS Duration, QT Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF)
time frame: Baseline (Day 1) and Day 14
description: Triplicate 12-lead electrocardiograms (ECG) were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Spirometry: Forced Expiratory Volume in One Second (FEV1) at Indicated Time Points
time frame: Day 1 and Day 14
description: FEV1 is the amount of air that can be forcefully exhaled from the lungs in the first second of a forced exhalation. It was measured by spirometry test. Mean and standard deviation data of FEV1 measured at Day 1 and Day 14 have been presented.
measure: Spirometry: Forced Vital Capacity (FVC) at Indicated Time Points
time frame: Day 1 and Day 14
description: FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. Mean and standard deviation data of FVC measured at Day 1 and Day 14 have been presented.
measure: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Counts, Total Neutrophils, White Blood Cell (WBC) Count
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets counts, Total neutrophils and WBC count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Hematology Parameter: Hematocrit
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Hematology Parameter: Hemoglobin
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Hematology Parameter: Mean Corpuscular Volume
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Volume. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Hematology Parameter: Red Blood Cell Count
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected to analyze the hematology parameter: Red Blood Cell count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Urea
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected to analyze the chemistry parameters: Calcium, Glucose, Potassium, Sodium and Urea. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Chemistry Parameters: Creatinine, Direct Bilirubin, Total Bilirubin
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected to analyze the chemistry parameters: Creatinine, Direct Bilirubin and Total Bilirubin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Urinalysis Parameter: Specific Gravity
time frame: Baseline (Day 1) and Day 14
description: Urinary specific gravity measurement is a part of routine urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)
time frame: Baseline (Day 1) and Day 14
description: Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Sputum Resistin Levels
time frame: Baseline (Day 1), Day 7 and Day 14
description: Sputum samples were collected at indicated time points to analyze resistin levels. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in the Ratio of Sputum NETs to Sputum Neutrophils
time frame: Baseline (Day 1) and Day 14
description: Sputum samples were collected to calculate ratio of sputum NETs to sputum neutrophils. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value. The ratio is calculated as the sputum NETs divided by the number of sputum neutrophils.
measure: Change From Baseline in Sputum Elastase Activity
time frame: Baseline (Day 1), Day 7 and Day 14
description: Sputum samples were collected at indicated time points to analyze sputum elastase activity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by DNA Release
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by DNA release. DNA-elastase complexes quantified NETs formation. Phorbol 12-myristate 13-acetate (PMA) was used to induce inflammation and NETs formation in the PMA stimulated samples. Blood from participants were tested at Baseline and Day 14 for non-PMA stimulated samples, and at Baseline and Day 14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally (non PMA induced) or where NETs formation was already raised (PMA stimulated). Hence participants were counted in both the categories - PMA stimulated and not PMA stimulated. NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
measure: Percentage Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by Microscopy
time frame: Baseline (Day 1) and Day 14
description: Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by microscopy.DNA-elastase complexes quantified NETs formation.PMA was used to induce inflammation and NETs formation in PMA stimulated samples. Blood from participants were tested at Baseline and Day14 for non-PMA stimulated samples,and at Baseline and Day14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally(non PMA induced)or where NETs formation was already raised(PMA stimulated).Participants were counted in both categories-PMA stimulated and not PMA stimulated.NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA.Baseline was considered as Day1.Change from Baseline was calculated as post-Baseline value minus Baseline value.Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by100.
measure: Maximum Observed Concentration (Cmax) of Danirixin
time frame: Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
description: Blood samples were collected to evaluate the pharmacokinetic (PK) of danirixin at the indicated time points for the analysis of Cmax. PK population consisted of all participants in the Modified Intent-To-Treat population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values).
measure: Time to Cmax (Tmax) of Danirixin
time frame: Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
description: Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tmax.
measure: Area Under the Blood Concentration-time Curve [AUC(0-t)] of Danirixin
time frame: Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
description: Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of AUC(0-t).
measure: Time of Last Observed Concentration (Tlast) of Danirixin
time frame: Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
description: Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tlast.
arm group label: Danirixin 35 mg
arm group type: Experimental
description: Eligible subjects will receive danirixin 35 mg tablet with food twice daily for 14 Days.
arm group label: Placebo Comparator
arm group type: Experimental
description: Eligible subjects will receive placebo tablet with food twice daily for 14 Days.
intervention type: Drug
intervention name: Danirixin
description: Danirixin will be available as 35 mg oval shaped, white film coated HBr embossed tablets.
arm group label: Danirixin 35 mg
intervention type: Drug
intervention name: Placebo
description: Placebo will be available as oval shaped, white film coated tablets.
arm group label: Placebo Comparator
intervention type: Drug
intervention name: Rescue medication
description: Subjects may continue to use rescue medication(s) anytime during the study. The following rescue medications may be used: short acting beta agonists, short acting muscarinic antagonists, or short acting combination bronchodilators.
arm group label: Danirixin 35 mg
arm group label: Placebo Comparator
intervention type: Drug
intervention name: Inhaled COPD maintenance medication
description: Subjects may continue to use inhaled COPD maintenance medication(s) during the study, at the discretion of the GSK Medical Monitor and/or Investigator. The following maintenance medications may be used: long acting bronchodilator medications (e.g. long-acting muscarinic antagonist [LAMA], long-acting beta-agonist [LABA]) and long-acting bronchodilator combination therapies (e.g. LAMA/LABA) and long-acting bronchodilator/inhaled corticosteroid steroid combination (ICS) therapies (e.g. LABA/ICS, LAMA/LABA/ICS)
arm group label: Danirixin 35 mg
arm group label: Placebo Comparator
criteria: 
gender: All
minimum age: 50 Years
maximum age: 75 Years
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United Kingdom
citation: Keir HR, Richardson H, Fillmore C, Shoemark A, Lazaar AL, Miller BE, Tal-Singer R, Chalmers JD, Mohan D. CXCL-8-dependent and -independent neutrophil activation in COPD: experiences from a pilot study of the CXCR2 antagonist danirixin. ERJ Open Res. 2020 Nov 10;6(4):00583-2020. doi: 10.1183/23120541.00583-2020. eCollection 2020 Oct.
PMID: 33263062
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: Yes
ipd description: IPD for this study is available via the Clinical Study Data Request site.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
ipd access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
ipd url: https://clinicalstudydatarequest.com/Posting.aspx?ID=20764
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 