Investigation of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Efficacy of Oral Danirixin in Symptomatic COPD Subjects With Mild to Moderate Airflow Limitation at Risk for Exacerbations

Inclusion Criteria

• Male or female aged between 40 and 70 years of age inclusive, at the time of signing the informed consent
• Subjects with a documented history of COPD exacerbation(s) in the 12 months prior to study participation meeting at least one of the following criteria: >=2 COPD exacerbations resulting in prescription for antibiotics and/or oral corticosteroids or hospitalization or extended observation in a hospital emergency room or outpatient center; 1 COPD exacerbation resulting in prescription for antibiotics and/or oral corticosteroids or hospitalization or extended observation in a hospital emergency room or outpatient center and a plasma fibrinogen concentration at screening >=3.5 milligram/milliliter (mg/mL)
• Diagnosis of symptomatic chronic obstructive pulmonary disease with mild to moderate airflow obstruction (COPD-GOLD I or II) for at least 2 years based on American Thoracic Society (ATS)/ European Respiratory Society (ERS) current guidelines or symptoms consistent with COPD for at least 2 years
• Subjects with a post-bronchodilator FEV1/FVC ratio of =50% of predicted normal value calculated using National Health and Nutrition Examination Survey (NHANES) III reference equation at Visit 1
• A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli international units/mL (MIU/mL) and estradiol =45 kilogram (kg)
• Current smokers and former smokers with a cigarette smoking history of >=10 pack years (1 pack year =20 cigarettes smoked per day for 1 year or equivalent). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1
• Subjects with a history of respiratory symptoms, including chronic cough and/or mucus hypersecretion on most days for at least the previous 3 months prior to Visit 1
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits; For US sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• Current or expected use of proton pump inhibitors or histamine H2-receptor antagonists during the study period
• Chest X-ray (posteroanterior with lateral) or CT scan reveals evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD (historic data up to 1 yr may be used).
• Subjects with peripheral blood neutrophil count (PBN) <2x10^9/Liter
• Subject with history of previous lung surgery (e.g. lobectomy, pneumonectomy, or lung volume reduction)
• Requiring the use of oral or injectable Cytochrome P450 3A4 (CYP3A4) or breast cancer resistance protein (BCRP) substrates with a narrow therapeutic index