A Study Evaluating the Efficacy of Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dosed Inhaler on Cardiopulmonary Outcomes in Chronic Obstructive Pulmonary Disease

Inclusion criteria

• Male or female participants must be 40 to 80 years of age inclusive, at the time of signing the ICF.
• Demonstrate acceptable MDI administration technique at Visit 1 (V1) and Visit 2 (V2)
• A diagnosis of COPD confirmed by a post-bronchodilator FEV1/FVC ratio \< 70% at V1.
• Current or former smokers with a history of at least 10 pack-years of cigarette smoking; defined as (number of cigarettes per day/20) x number of years smoked. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to V1.
• A baseline peripheral blood eosinophil count of ≥ 100 cells/mm3 assessed at Visit 1 by the central laboratory
• A CAT score of ≥ 10 at Visit 1.
• Participant must fulfill at least 1 of the 4 CV disease/risk factor criteria below \[(a), (b), (c), or (d)\]:
• : Established CV Disease
• : Combination of CV risk factors:
• Hypertension
• Diabetes Mellitus
• Chronic Kidney Disease
• Dyslipidemia
• : High risk of CV disease determined using an established CV risk assessment tool.
• : CT coronary Artery Calcification
• Willing and, in the opinion of the investigator, able to adjust current COPD therapy, as required by the protocol.
• Willing to visit at the study site or participate in virtual visits as required per the protocol to complete all study assessments.
• A female is eligible to enter and participate in the study if the female is of:
• Non-childbearing potential: either permanently sterilized or who are post-menopausal.
• Childbearing potential: has a negative serum pregnancy test at V1 and must use one highly effective form of birth control.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.

Exclusion criteria

• Active diagnosis of asthma within the past 5 years (previous diagnosis as a child or adolescent are eligible), asthma-COPD overlap, or any other chronic respiratory disease other than COPD such as alpha-1 antitrypsin deficiency, active tuberculosis, lung fibrosis, sarcoidosis, interstitial lung disease, and pulmonary hypertension.
• End-stage renal disease requiring renal replacement therapy
• History of heart or lung transplant or actively listed for heart or lung transplant.
• Implanted left ventricular assist device or implant anticipated in \< 3 months.
• History of lung cancer and/or treatment for lung cancer within the 5 years prior to Visit 1.
• Unstable or life-threatening cardiac disease - participants with any of the following at Visit 1 would be excluded:
• An MI or unstable angina in the last 8 weeks
• Unstable or life-threatening cardiac arrhythmia requiring intervention in the last 8 weeks. NOTE: Any participant who experiences unstable or life-threatening cardiac disease during the run-in period will be excluded but can be rescreened 8 weeks after the resolution of the event.
• Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 8 weeks prior to Visit 1
• Any life-threatening condition, including malignancy, with a life expectancy \< 5 years, other than CV disease or COPD, that might prevent the participant from completing the study.
• Use of maintenance ICS treatment within the past 12 months.
• Unable to abstain from protocol-defined prohibited medications
• Participation in another clinical study with a study intervention administered in the last 30 days or 5 half-lives, whichever is longer prior to Visit 1 (any other investigational product that is not identified in protocol is prohibited for use during the duration of the study).
• Participants with a known hypersensitivity to LAMA, LABA or ICS or any component of the MDI.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
• Previous randomization in the present study.
• For females only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding