Long-term efficacy and safety of aclidinium bromide/formoterol fumarate Fixed-Dose Combination

Exclusion Criteria

• - History or current diagnosis of asthma.
• - Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the 6 weeks before Screening Visit.
• - Patient hospitalised for COPD exacerbation within 3 months prior to Screening Visit.
• - Clinically significant respiratory conditions defined as:
• • Known active tuberculosis.
• • History of interstitial lung or massive pulmonary thromboembolic disease.
• • Pulmonary resection or lung volume reduction surgery within 12 months prior to Screening Visit.
• • History of lung transplantation.
• • History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic fibrosis, Kartagener's syndrome, etc).
• • Known a1-antitrypsin deficiency.
• - Patients who in the Investigator’s opinion might have needed to start a pulmonary rehabilitation
• program during the study and/or patients who started/finished it within 3 months prior to screening.
• - Use of long-term oxygen therapy (≥ 15 hours/day).
• - Patients who did not maintain regular day/night, waking/sleeping cycles including night shift workers (eg, history of sleep apnoea syndrome, any condition related to sleep disturbances such as restless-legs syndrome or somnambulism).
• - Clinically significant cardiovascular conditions defined as:
• • Myocardial infarction within the 6 months prior to screening.
• • Thoracic surgery within 12 months prior to screening.
• • Unstable angina or unstable arrhythmia which had required changes in the pharmacological therapy or other intervention within 12 months prior to screening, or newly diagnosed arrhythmia within the previous 3 months prior to screening.
• • Hospitalisation within 12 months prior to screening 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.
• - Patients (with or without pharmacological therapy) with resting systolic blood pressure (SBP)
• ≥200 mmHg, a resting diastolic blood pressure (DBP) ≥120 mmHg, or a resting heart rate ≥105 beats
• per minute (bpm) at screening and at Visit 1 prior to randomisation.
• - Patients with interval corrected for heart rate "QTc" [calculated according to formulae (QTc=QT/RR1/2) > 470 msec as indicated in the centralised reading report assessed at Screening Visit.
• - Patients with clinically relevant abnormalities in the clinical laboratory tests, ECG parameters (other
• than QT interval corrected using Bazett’s formula [QTcB]) or in the physical examination at screening,
• if the abnormality defined a disease state listed as exclusion criteria, except for those related to COPD.
• - Patients with a history of hypersensitivity reactions to inhaled anticholinergics, sympathomimetic amines, or inhaled medication or any component thereof (including report of paradoxical bronchospasm). Patients with known narrow-angle glaucoma, symptomatic bladder neck obstruction or acute urinary retention.
• - Patients with symptomatic non-stable prostate hypertrophy. (However, patients with well-controlled, stable, asymptomatic benign prostatic hypertrophy were not excluded).
• - Patients with known uncontrolled history of infection with human immunodeficiency virus and/or active hepatitis.
• - Current diagnosis of cancer other than basal or squamous cell skin cancer.
• - Life expectancy of less than 1 year.
• - Patients with any other serious or uncontrolled physical or mental dysfunction that, as judged by the Investigator, could have placed the patient at higher risk from his/her participation in the study, could have confounded the results of the study, or is likely to prevent the patient from complying with the requirements of the study, or completing the study.
• - Patients with a history (within 2 years prior to screening) of drug and/or alcohol abuse that might have prevented study compliance based on the Investigator judgment.
• - Patients unlikely to be cooperative (eg, take the medication, complete the Patient Diaries or attend the clinic at the required times).
• - Patients unable to properly use a DPI or pMDI inhaler device or to perform spirometry measurements.
• - Patients previously randomised in a study involving aclidinium bromide/formoterol FDC.
• - Patients previously randomised in a study involving aclidinium bromide monotherapy except when participation finished at least 6 months before screening.
• - Patients treated with any investigational drug within 30 days (or 6 half-lives, whichever is longer) prior to screening.
• - Patients who intended to use any concomitant medication not permitted by this protocol or who had not undergone the required washout period for a particular prohibited medication.
• - Patients unable to give consent, or patients of consenting age but under guardianship, or vulnerable patients.
• - Patients employed, or relatives of employees at the study centre, Almirall or Forest Laboratories.
• - Any other conditions that, in the Investigator’s opinion, might have indicated the patient to be unsuitable for the study.