• Safety Parameters: Adverse events, 12 Lead Electrocardiogram, Vital Signs, Clinical Laboratory Evaluations, [ Time Frame: after 28 days repeat dosing ]
  
• Lung Function Parameters, Holter monitoring, Withdrawals for exacerbations of COPD.
  

• Plasma concentrations of GSK256066 and active metabolite GSK614917 and derived pharmacokinetic parameters
  
• Parameters measured in induced sputum: Total cell number (cells/mL); Neutrophils, macrophages, lymphocytes and eosinophils as a percentage of total cells; Absolute numbers of neutrophils, macrophages, lymphocytes and eosinophils
  
• The concentration of total protein and inflammatory biomarkers in induced sputum supernatant
  
• Change from baseline in messenger ribonucleic acid (mRNA) and/or protein in induced sputum of established and exploratory markers of inflammation and established and exploratory pharmacodynamic markers
  
• Lung function parameters (pre and post-bronchodilator)
  
• Spirometry measures: FEV1, FVC Plethysmography measures Impulse oscillometry The concentration of serum inflammatory biomarkers
  
• Lung Function Parameters Holter monitoring Withdrawals for exacerbations of COPD
  

Inclusion Criteria:

• Male adults or female adults of non-childbearing potential who are between 40 and 75 years of age (inclusive).
• Subjects with a clinical diagnosis of COPD in accordance with the European Respiratory Society Consensus Statement and subjects categorised with moderate COPD as defined by the GOLD guidelines of 2006 [GOLD, 2006]
• Subjects with a cigarette smoking history of ≥ 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or the equivalent). Both current and former smokers are eligible to be enrolled. A former smoker is defined as a subject who has not smoked for ≥6 months at Visit 1.
• Subjects with a post-bronchodilator FEV1 to FVC ratio (FEV1/FVC) < 0.7 at Visit 1. Subjects will be assessed 30 (± 5) minutes after receiving salbutamol 400 μg.
• Subjects with a post-bronchodilator FEV1 ≥ 50% and < 80% of predicted normal for height, age and sex at Visit 1. Subjects will be assessed 30 (± 5) minutes after receiving salbutamol 400 μg.
• Subjects with a normal echocardiogram at screening, as defined by the absence of clinically significant wall motion, chamber size or valvular abnormalities
• The subject must be capable of giving informed consent and can comply with the study requirements and timetable.

Exclusion Criteria:

• Women who are pre-menopausal and of child-bearing potential.
• Subjects weighing less than 50 kilograms (kg).
• Subjects who are obese defined as having a body mass index (BMI) > 30.
• Subjects with a current diagnosis of asthma.
• Subjects who have required hospitalisation or treatment with oral corticosteroids and/or antibiotic therapy for acute worsening of COPD or lower respiratory tract infection in the 6 weeks prior to Screening.
• Subjects who have received treatment with oral, intravenous, topical or intra-articular corticosteroids within 6 weeks of Screening or thereafter
• Subjects with active tuberculosis, sarcoidosis or clinically overt bronchiectasis.
• Subjects with a history of any type of malignancy with the exception of successfully treated squamous cell cancer of the skin.
• Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with chronic inflammation (e.g. Inflammatory Bowel Disease).
• Subjects with chronic infections (lasting longer than 6 months) such as gingivitis, periodontitis, prostatitis, gastritis, and urinary tract infections.
• Subjects with any acute infection, sinus symptoms, or significant trauma (burns, fractures).
• Subjects with clinically significant renal disease, diabetes mellitus/metabolic syndrome, hypertension or any other clinically significant cardiovascular, neurological, endocrine, or haematological abnormalities that are uncontrolled on permitted therapy.
• Subjects who have participated in any GSK study/studies involving administration of COA.
• The subject has a screening ECG parameters outside of ranges specified in protocol.
• Subjects with hypoxaemia
• Risk factors for human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection at Screening (Visit 1).
• Subjects who have undergone surgery including lung volume reduction surgery in the last six months or have conditions that prevent them from performing spirometry.
• Subjects with a history (or suspected history) of alcohol misuse or any other recreational substance abuse.

• Subjects who require treatment with any of the following from the start of the run-in period (Day -14) until the end of the treatment phase:

  • Inhaled corticosteroids
  • Inhaled cromolyn sodium or nedocromil
  • Xanthines (theophylline preparations).
  • Leukotriene modifiers
  • Tiotropium
  • Long-acting inhaled beta2-agonists (salmeterol, formoterol)
  • Oral beta2-agonists
• Subjects who are unable to abstain from other courses of medication during the run in phase including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines, anti-rhinitis or hay fever medication, other than short acting inhaled beta-agonists, ipratropium bromide and paracetamol (up to 4 g per day) for the treatment of minor ailments (eg headache) from 48h before the first dose until the follow-up visit. Subjects requiring medication between dosing and follow up may be excluded at the principal investigators discretion.
• Subjects with any known hypersensitivity to salbutamol or ipratropium bromide.
• Subjects who are participating or plan to participate in the active phase of a pulmonary rehabilitation programme during the study.
• Subjects who have received an investigational drug within 30 days or within five drug half-lives of the investigational drug (whichever is longer).
• Subjects with any clinically relevant abnormality detected by the assessments at Screening.
• Subjects who have experienced an exacerbation during the run-in period requiring treatment with oral corticosteroids and/or macrolide antibiotics and/or hospitalisation.