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

Prior treatment

• 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.
• 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.
• Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 8 weeks prior to Visit 1
• 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).
• Previous randomization in the present study.

Other illness

• End-stage renal disease requiring renal replacement therapy
• History of heart or lung transplant or actively listed for heart or lung transplant.
• 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.
• Participants with a known hypersensitivity to LAMA, LABA or ICS or any component of the MDI.

Age

• 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.

Other

• Use of maintenance ICS treatment within the past 12 months.
• 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.
• For females only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding

• 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
  • Obesity
  • : 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.