Aclidinium/Formoterol Fixed Combination Dose finding Study

Exclusion Criteria

• 1. History or current diagnosis of asthma, allergic rhinitis or atopy, or exercise-induced
• bronchospasm.
• 2. Eosinophil count ≥600 cells/mm3.
• 3. Clinically significant respiratory conditions at the time of Screening Visit defined as:
• • Use of long-term oxygen therapy >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,
• 4. Hospitalisation due to COPD exacerbation, up to the 3 months prior to the Screening Visit.
• 5. Signs of a COPD exacerbation or respiratory infection (including the upper respiratory tract), up to the 6 weeks prior to the Screening Visit.
• 6. 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
• 7. 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).
• 8. Presence of narrow-angle glaucoma.
• 9. 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).
• 10. Life expectancy of less than 1 year.
• 11. 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.
• 12. 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.
• 13. Clinically significant diseases other than COPD, which, in the opinion of the Investigator, may have put the patient at risk because of the participation in the trial; or diseases which may have influenced the results of the study or the patient’s ability to take part in it.
• 14. Patients who did not maintain regular day/night, waking/sleeping cycles (eg, night shift workers were to be excluded).
• 15. Patients who intended to use any concomitant medication not permitted by the protocol or who had not undergone the required wash-out period for a particular prohibited medication.
• 16. Patients who were unable or unlikely to be cooperative with the study requirements of taking the medication, completion of the Patient Diary and attending the clinic for study visits.
• 17. Patients who were unable to properly use a dry powder or pressurised metered-dose inhalers (pMDI) inhaler device and/or to perform acceptable and reproducible spirometry measurements as per the ATS/ERS standards (Standardisation of lung function test, 2005 20).
• 18. History of drug and/or alcohol abuse or addiction during the previous 2 years.
• 19. Previous participation in another clinical trial with any investigational medicinal product 6 weeks prior to the Screening Visit. (Patients who had participated in a previous clinical trial with aclidinium bromide (Almirall product code LAS34273) were to be allowed to participate in this study provided that the above criterion was fulfilled. This circumstance was to be specifically recorded on the eCRF).