Efficacy, Pharmacokinetics (PK), Safety and Tolerability Study of inhaled AZD8871

Exclusion Criteria

• 1. Patient previously enrolled in the present study.
• 2. Patient has significant diseases other than COPD, ie, disease or condition or an abnormality in laboratory, ECG, medical history or physical examination which, in the opinion of the Investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the patient’spatient's ability to participate in the study.
• 3. Childbearing potential female, pregnant or lactating.
• 4. Patient who, in the opinion of the Investigator, has a current diagnosis of asthma.
• 5. Patient has alpha-1 antitrypsin deficiency as the cause of COPD.
• 6. Patient has other active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or uncontrolled sleep apnoea. Allergic rhinitis is not exclusionary.
• 7. Lung surgery for volume reduction or lung transplantation: Patient has undergone lung volume reduction surgery, lobectomy, or bronchoscopic lung volume reduction (endobronchial blockers, airway bypass, endobronchial valves, thermal vapour ablation, biological sealants, massive pulmonary embolism and airway implants) within 1 year of Screening (Visit 1).
• 8. Patient is using nocturnal positive pressure (eg, continuous positive airway pressure or bi level positive airway pressure). Patient is using any non-invasive positive pressure ventilation device.
• Note: A patient using continuous positive airway pressure or bi level positive airway pressure for Sleep Apnoea Syndrome is allowed in the study.
• 9. Patient has been hospitalised due to poorly controlled COPD within 3 months of Screening.
• 10. Patient has acute worsening of COPD that requires treatment with corticosteroids or antibiotics in the 6 week interval prior to Screening (Visit 1), or during the Screening Period (between Visits 1 and 3).
• 11. Patient has had lower respiratory tract infections that required antibiotics within 6 weeks prior to Screening.
• 12. Patient cannot perform acceptable spirometry, ie, meet American Thoracic Society (ATS)/European Respiratory Society (ERS) acceptability criteria.
• 13. Patient has changed their smoking status (ie, start or stop smoking) or initiation of a smoking cessation program within 6 weeks prior to Screening.
• 14. Patient has participated in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening or who will enter the acute phase of a pulmonary rehabilitation program during the study. A patient in the maintenance phase of a pulmonary rehabilitation program is not to be excluded.
• 15. Cardiac disease: Subject with significant cardiovascular disease cardiovascular instability. Patient with heart rate <50 beats per minute. Patient has clinically significant uncontrolled hypertension as assessed by the investigator.
• 16. Neurological: Patient with seizures or history of seizures requiring anticonvulsants within 12 months prior to Screening. Patient is taking selective serotonin reuptake inhibitors or serotonin–-norepinephrine reuptake inhibitors whose dose has not been stable for at least 4 weeks prior to Screening, or exceeds the maximum recommended dose.
• 17. Renal: Patient with symptomatic bladder neck obstruction, acute urinary retention or symptomatic non-stable prostate hypertrophy. 35.23. Patient with a serum potassium value <3.5 mmol/L at Screening and on repeat testing. Note: however potassium replacement and rescreening is allowed if serum potassium concentration was < 3.5mmol/l at screening.
• 18. Others:
• -Any laboratory abnormality or suspicion of any clinically relevant disease or disorder (on history or examination), including uncontrolled hypertension or uncontrolled diabetes, which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study, or any other safety concerns in the opinion of the Investigator.
• - History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localized basal cell carcinoma of the skin
• -Patient with known narrow-angle glaucoma.
• -Patient has a history of hypersensitivity to β2-agonists, muscarinic anticholinergics or lactose/milk protein. Lactose intolerance is not an exclusion criterion.
• -The patient has a known or suspected history of alcohol or drug of abuse within the past 2-year period years or consuming more than 14 (female subjects) or 21 (male subjects) units of alcohol a week, or shows positive for drugs of abuse and alcohol tests at screening and prior to randomization.
• -Patient who, in the opinion of the Investigator, would be unable to abstain from protocol-defined prohibited medications during the study.
• -Patient who received a live attenuated vaccination within 30 days prior to Screening.
• -Patient involved in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• -Patient treated with investigational drug or device in another clinical trial within the last 30 days or five half-lives (whichever is longer) prior to Screening.
• -Patient who donated or lost >500 mL of blood and plasma within the previous 3 months prior to screening.
• -Patient is unlikely to co-operate with the requirements of the study, instructions of the Principal Investigator., or have e-dairy completion rate of < 70% during the run in period.
• -Patient with known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C infection.