Aclidinium/Formoterol Fixed Combination Dose Finding Study

Inclusion Criteria

• Adult males or non-pregnant, non-lactating females aged between 40 and 80 years old, both inclusive. Women of childbearing potential were allowed to enter the trial only if they used two medically approved contraceptive measures (ie, mechanical and pharmacological).

(A female was considered to be of childbearing potential unless she had a hysterectomy, was at least one year post-menopause or had undergone tubal ligation. All women of childbearing potential were to have a negative serum pregnancy test at the Screening Visit).

• Patients with a clinical diagnosis of stable moderate to severe COPD (stages II and III) according to the GOLD 2006 classification (http://www.goldcopd.com).
• Current or ex-cigarette smoker with a smoking history of at least 10 pack-years.

Pack-years were calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person had smoked. For example, a person who smoked 40 cigarettes a day and had smoked for 10 years would have had a 20 pack-year smoking history (40 cigarettes per day ÷ 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history).

Patients smoking other tobacco types were not allowed, unless they met the cigarette criterion as well.

• Patients whose Forced Expiratory Volume in 1 second (FEV1) at the Screening Visit measured between 30-45 minutes post inhalation of 400 μg of salbutamol was 30% ≤FEV1 5 h/day,
• Known active tuberculosis,
• History of interstitial lung or pulmonary thromboembolic disease,
• Pulmonary resection during the past 12 months,
• History of life-threatening COPD,
• History of bronchiectasis secondary to respiratory diseases others than COPD (eg, cystic fibrosis, Kartagener's syndrome, etc),
• Patients who in the Investigator's opinion may have needed to stop or start pulmonary rehabilitation or undergo a thoracotomy during the trial,
• Hospitalisation due to COPD exacerbation, up to the 3 months prior to the Screening Visit.
• Signs of a COPD exacerbation or respiratory infection (including the upper respiratory tract), up to the 6 weeks prior to the Screening Visit.
• Clinically significant cardiovascular conditions at the time of Screening Visit defined as:
• Myocardial infarction within the previous 6 months,
• Unstable arrhythmia which has required changes in the pharmacological therapy or other intervention within the previous 12 months, or newly diagnosed arrhythmia within the previous 3 months.
• Hospitalisation within the previous 12 months for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at any physical activity and presence of symptoms at rest) as per the New York Heart Association classification (www.americanheart.org)
• Thoracic surgery within the previous 24 months
• Presence of symptomatic prostatic hypertrophy and/or bladder neck obstruction. (However, patients who had a diagnosis of these conditions but without symptoms due to stable concomitant medication for its treatment were allowed to enter trial).
• Presence of narrow-angle glaucoma.
• History of untoward reactions or known hypersensitivity to inhaled anticholinergics (including aclidinium bromide), β2 adrenergic agonists or inhaled medication or any component thereof (including report of paradoxical bronchospasm).
• Life expectancy of less than 1 year.
• Prolonged QT interval corrected using Bazett's formula (QTcB) interval (>470 msec) in any of the ECGs performed before randomisation, and/or the use of drugs which may have induced its prolongation.
• Clinically relevant abnormalities in laboratory results, ECG parameters (other than QTcB), or physical examination if the abnormality defines a disease state listed as an exclusion criterion, except for those related to COPD.
• Clinically significant diseases other than C