An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention.

ECG parameters consist of QT interval corrected by Bazett's (QTcB) and Fridericia's (QTcF) formulas, QT interval, QRS duration and PR interval. Baseline was defined as value at Day 0 (pre-bronchodilator). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was the mean of the 3 pre-salbutamol measurements at Day 0. It was assessed on Baseline, Day 1, 7, 14, 15, 21, 27 and 28. Post Baseline, ECG was performed 1-2 hours post dose.

ECG parameters consist of ventricular rate. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was the mean of the 3 pre-salbutamol measurements at Day 0. It was as/sessed on Baseline, Day 1, 7, 14, 15, 21, 27 and 28. Post Baseline, ECG was performed 1-2 hours post dose.

The PCI range for SBP was \< 85 and \> 160 millimeters of mercury (mmHg), DBP was \< 45 and \> 100 mmHg and for HR \< 40 and \> 110 beats per minute. It was assessed on Baseline (pre-bronchodilator), Day 14 and 27. Data for SBP high, SBP low, DBP high, DBP low, HR high and HR low is presented.

Clinical chemistry included: albumin, bicarbonate, alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), blood urea, creatinine, magnesium, sodium, potassium, chloride, glucose, total bilirubin, direct bilirubin, indirect bilirubin, total protein, gamma glutamyltransferase (GGT), calcium, creatinine kinase, creatine kinase-MB, creatinine clearance (estimated; male and female), lactate dehydragenase, and troponin, triglycerides. Data for abnormal parameters (above and below range) is provided. It was assessed on Baseline (Day -3), Day 14, 28 and on follow up visit (Day 42). Data for only abnormal observations is presented.

Hematology included: haemoglobin, haematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell (RBC) indices, white blood cell (WBC), basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. Data for abnormal parameters (above and below range) is provided. It was assessed on Baseline (Day -3), Day 14, 28 and on follow up visit (Day 42). Data for only abnormal observations is presented.

Abnormal urinalysis data for RBC in urine and haematuria presented. Data for abnormal parameters (above and below range) is provided. It was assessed on Baseline (Day -3), Day 7, 14, 21, 28 and on follow up visit (Day 42). Data for only abnormal observations is presented.

The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline value defined as the value on Day 0. It was assessed on Baseline (Day 0), Day 14 and 27. Spirometry tests was performed before and 30 minutes after dosing with salbutamol (bronchodilator) on Day 0 and before dosing with GSK256066. As they were analyzed separately, there were two Baselines for these tests, 'pre bronchodilator Baseline' and 'post bronchodilator Baseline'. Smoking and short acting bronchodilators were avoided 6 hour prior to administration of the salbutamol. Observations with best test review (BTR) grading of 'not acceptable' were excluded.

Holter parameters were derived by visit over the 24 hour period as: maximum HR over 24 hours was the maximum HR of all time slices and mean HR over 24 hours was the mean HR of all time slices, weighted by the time length of each slice. The total number of ventricular runs and the number of supraventricular runs over 24 hours were derived by summing each count across all time slices. Data for normal, abnormal: not clinically significant and abnormal: clinically significant is presented. It was assessed on Baseline (Day 0), Day 14and 27. Data for normal, abnormal: clinically significant and abnormal: clinically not significant presented.

An exacerbation of COPD was defined as worsening of COPD symptoms requiring changes to normal treatment including antimicrobial therapy, short courses of oral steroids and other bronchodilator therapy. If clinically indicated, short-term treatment with antibiotics could be prescribed for the exacerbation. Any participants requiring treatment with inhaled or oral corticosteroids or admission to hospital were withdrawn from the study.