Patients were randomised if they met the following main inclusion criteria: outpatients aged ≥40 years with a history of moderate to very severe COPD (GOLD stage 2–4) [23 ]; post-bronchodilator FEV1 <80% of predicted normal; post-bronchodilator FEV1/forced vital capacity (FVC) <70%; current or ex-smokers with a smoking history of >10 pack–years.
Patients with a significant disease other than COPD were excluded from the trials. Other exclusion criteria included: clinically relevant abnormal baseline laboratory parameters or a history of asthma; myocardial infarction within 1 year of screening; unstable or life-threatening cardiac arrhythmia; known active tuberculosis; clinically evident bronchiectasis; cystic fibrosis or life-threatening pulmonary obstruction; hospitalised for heart failure within the past year; diagnosed thyrotoxicosis or paroxysmal tachycardia; previous thoracotomy with pulmonary resection; regular use of daytime oxygen if patients were unable to abstain during clinic visits; or currently enrolled in a pulmonary rehabilitation programme (or completed in the 6 weeks before screening).
Patients with moderate or severe renal impairment (creatinine clearance ≤50 mL·min−1) were not excluded from the study but were closely monitored by the investigator.
Both studies were performed in accordance with the Declaration of Helsinki, International Conference on Harmonisation Harmonised Tripartite Guideline for Good Clinical Practice and local regulations. The protocols were approved by the authorities and the ethics committees of the respective institutions, and signed informed consent was obtained from all patients.
Patients with a significant disease other than COPD were excluded from the trials. Other exclusion criteria included: clinically relevant abnormal baseline laboratory parameters or a history of asthma; myocardial infarction within 1 year of screening; unstable or life-threatening cardiac arrhythmia; known active tuberculosis; clinically evident bronchiectasis; cystic fibrosis or life-threatening pulmonary obstruction; hospitalised for heart failure within the past year; diagnosed thyrotoxicosis or paroxysmal tachycardia; previous thoracotomy with pulmonary resection; regular use of daytime oxygen if patients were unable to abstain during clinic visits; or currently enrolled in a pulmonary rehabilitation programme (or completed in the 6 weeks before screening).
Patients with moderate or severe renal impairment (creatinine clearance ≤50 mL·min−1) were not excluded from the study but were closely monitored by the investigator.
Both studies were performed in accordance with the Declaration of Helsinki, International Conference on Harmonisation Harmonised Tripartite Guideline for Good Clinical Practice and local regulations. The protocols were approved by the authorities and the ethics committees of the respective institutions, and signed informed consent was obtained from all patients.
