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 < 0.7 and FEV1 >=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 <
40 picogram (pg)/mL (<147 picomole/Liter [pmol/L]) is confirmatory]. Females on
hormone replacement therapy (HRT) will not be enrolled in the study.

- Body weight >=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) <2x upper limit
of normal (ULN); alkaline phosphatase and bilirubin <=1.5xULN (isolated bilirubin
>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

- Able to perform lung function tests reliably

- Based on single or averaged corrected QT (QTc) values of triplicate ECGs obtained
over a brief recording period: Fridericia-corrected QTc (QTcF) < 450 milliseconds
(msec); or QTc < 480 msec in subjects with Bundle Branch Block

- Subjects must have the ability to use an electronic diary on a daily basis [Part B
only]

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form

Exclusion Criteria:

- Diagnosis of asthma, or other clinically relevant lung disease (other than COPD),
e.g. sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis or lung
cancer; Subject with alpha-1-antitrypsin deficiency as the underlying cause of COPD

- Pulse Oximetry levels <88% (at rest on room air) at screening

- Less than 14 days have elapsed from completion of a course of antibiotics or oral
corticosteroids for a recent COPD exacerbation.

- Diagnosis of Pneumonia (chest X-Ray or computed tomography [CT] confirmed) within the
last 3 months prior to screening

- History or current evidence of clinically significant renal disease, diabetes
mellitus/metabolic syndrome, hypertension or any other clinically significant
cardiovascular, neurological, endocrine, or hematological abnormalities that are
uncontrolled on permitted therapy. Significant is defined as any disease that, in the
opinion of the Investigator, would put the safety of the subjects at risk through
study participation, or which would affect the safety analysis or other analysis if
the disease/condition exacerbated during the study.

- A positive pre-study drug/alcohol screen

- A positive test for human immunodeficiency virus (HIV) antibody

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or GSK
Medical Monitor, contraindicates their participation

- Current or chronic history of liver disease, or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

- History of regular alcohol consumption within 6 months of the study defined as: For
non United States of America (US) sites: an average weekly intake of >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