Inclusion criteria:

• Subject must have a diagnosis of COPD based on the American Thoracic Society (ATS)/ European Respiratory Society (ERS) criteria.
• Male or female subjects, aged ? 40 years. Females must be of Non Child Bearing Potential. The definition of Non Child Bearing Potential is as following: Females, regardless of their age, with functioning ovaries and who have a current documented tubal ligation or hysterectomy, or females who are post-menopausal.
• Have diagnosed COPD stage III or IV according to GOLD criteria: a baseline post-bronchodilator FEV1 < 50% of predicted normal and a baseline post- bronchodilator FEV1/IVC ratio < 70%.
• Have experienced at least 2 moderate or severe COPD exacerbations leading to medical consultation (requiring oral corticosteroids or increasing dosage of oral corticosteroids and/or antibiotics or hospitalization) within the 12 months preceding Visit 1.
• Have stable COPD medication within 4 weeks prior to Visit 1 (no new medication added and no dosage changes in medication).
• Current or ex-smokers with a smoking history of ? 10 pack years (number of pack years = [number of cigarettes per day / 20] x number of years smoked, e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years).
• Are currently managed at home (outpatients), are ambulatory and able to travel to the clinic. Subjects can be treated with all relevant COPD medication (refer to Section 5.6 for details on allowed concomitant medication) including long-acting anticholinergics (Tiotropiumbromide), non-invasive ventilation, long term oxygen therapy and can have Cor Pulmonale.
• A signed and dated written informed consent is obtained prior to participation.
• Able to comply with the requirements of the protocol and be available for study visits over 52 weeks.

Exclusion criteria:

• Known other respiratory disorders or signs for other respiratory disorders (e.g. asthma, lung cancer, sarcoidosis, tuberculosis, lung fibrosis, cystic fibrosis, bronchoectasis).
• Known history of significant inflammatory disease, other than COPD (e.g. rheumatoid arthritis and systemic lupus erythematosus).
• Known to be severely alpha-1-antitrypsin deficient (PI SZ or ZZ)
• Having undergone lung surgery (e.g. lung resection including lung volume reduction surgery, lung transplant) or subjects scheduled for surgery.
• Concurrent medication from Visit 1 and for the duration of the study with any of the prohibited medications listed in Section 5.6.2
• Subjects receiving chronic or prophylactic antibiotic therapy.
• Serious, uncontrolled disease (including serious psychological disorders) likely to interfere with the study or impact on subject safety.
• Have, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse.
• History of depression.
• History or presence of clinically significant drug sensitivity or clinically significant allergic reaction to corticosteroids or salmeterol.
• Moderate or severe COPD exacerbation (requiring corticosteroids or increased dosage of corticosteroids and/or antibiotics or hospitalization) within the 4 weeks prior to Visit 1
• Lower respiratory tract infection within the 4 weeks prior to Visit 1 .
• Pregnant or lactating female and female of childbearing potential.
• Subject is a participating investigator, sub-investigator, study coordinator, or other employee of a participating investigator, or is an immediate family member of the before mentioned. Subject is an employee of GSK.
• Subject participated in an investigational drug study within 30 days prior to Visit 1