Randomized Study Evaluating the Effect of Danirixin on Neutrophil Extracellular Traps (NETs) in Chronic Obstructive Pulmonary Disease (COPD)

Exclusion Criteria

• •Primary clinical diagnoses of any of the following relevant lung diseases; asthma, sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis or lung cancer.
• •Known alpha-1-antitrypsin deficiency.
• •Pulse oximetry \<88% at rest at screening. Subjects should be tested while breathing room air.
• •Subjects on long term oxygen therapy (defined as \>15 hours/day of oxygen use).
• •Unstable co-morbidities (e.g. cardiovascular disease, active malignancy) which in the opinion of the Investigator would make the subject unsuitable to be enrolled in the study. This includes any abnormality identified on screening bloods or screening ECG which in the opinion of the Investigator would make the subject unsuitable for the study.
• •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 of GSK medical monitor, contraindicates their participation.
• •Current or chronic history of liver disease, or know hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• •Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years.
• •Antibiotic use concurrently or within 28 days preceding the screening visit, including current or planned chronic use of macrolide antibiotics during the study period for the prevention of COPD exacerbations. Examples of chronic use include daily or two-three times per week for at least 3 months.
• •Systemic immunosuppressive medication, including current oral corticosteroids at a dose \>5 milligram (mg), concurrently or within 28 days preceding the screening visit.
• •Oral or injectable Cytochrome P450 (CYP) 3A4 or Breast Cancer Resistance Protein (BCRP) substrates with narrow therapeutic index (CYP3A4 substrates include, but are not limited to, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, and theophylline; BCRP substrates include: Methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan.
• •Current use of phosphodiesterase-4 inhibitors: Roflumilast, Crisaborole and Apremilast.
• •Current use of Raloxifene.
• •Current use of low molecular weight heparin.
• •The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half lives, or twice the duration of the biological effect of the investigational product (whichever is longer).
• •Exposure to more than four investigational products within 12 months prior to the first dosing day.
• •Subjects with a peripheral blood neutrophil count \< 1.0x10\^9/liter (L) at screening.
• •Diagnosis of pneumonia (chest X-ray or computed tomography \[CT\] confirmed) within the 3 months prior to screening.
• •Chest X-ray (posterior with lateral) or CT scan reveals evidence of a clinically significant abnormality not believed to be due to the presence of COPD (historic data up to 1 year may be used).
• •Abnormal and clinically significant 12-lead ECG finding at screening. The investigator will determine the clinical significance of each abnormal ECG finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. An abnormal and clinically significant finding that would preclude a subject from entering the trial is defined as a 12-lead tracing that is interpreted as, but not limited to, any of the following:
• •AF with rapid ventricular rate \> 120 beats per minute (bpm);
• •Sustained or non-sustained ventricular tachycardia (VT);
• •Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator has been implanted);
• •QT interval corrected for heart rate by Fridericia's formula (QTcF) \>=500 millisecond (msec) in subjects with QRS \<120 msec and QTcF \>=530 msec in subjects with QRS \>=120 msec.
• •Affiliation with a study site: study investigators, sub-investigators, study coordinators, employees of a study investigator, sub-investigator or study site, or immediate family members of any of the above that is involved with the study.