A Study to Investigate the Effect on Lung Function of an Approved COPD Treatment (BGF, With HFA Propellant) Compared to BGF Formulated With a New Propellant (HFO) in Participants 40 to 80 Years of Age With COPD

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

Age

1. Participants must be 40 to 80 years inclusive at the time of signing the ICF. Typeof Participant and Disease Characteristics

2. Participants who have a documented history of physician-diagnosed COPD as defined bythe ATS/ERS (Celli et al 2004).

3. Participants who have been receiving LABA, LAMA, LAMA/LABA, or ICS/LABA inhaledmaintenance therapies for the management of their COPD for at least 4 weeks prior toVisit 1, OR Participants who have been receiving SABA, SAMA, or SABA/SAMA eitherscheduled or as needed for at least 4 weeks prior to Visit 1, OR Participants whoare COPD treatment-naïve or have not received previously prescribed COPD treatmentin the 4 weeks prior to Visit 1.

4. At Visit 1: Participants with a blood eosinophil count < 300 cells/μL.

5. At Visit 1: Participants with a pre-bronchodilator FEV1 of < 80% predicted normal.

6. At Visit 2: Participants with a post-bronchodilator FEV1/FVC ratio of < 0.70 and apostbronchodilator FEV1 of ≥ 40% to < 80% predicted normal.

7. At Visit 3 (TP 1 Day 1): Participants with a pre-dose FEV1 of < 80% predicted normalthat is within ± 20% or 200 mL of their Visit 2 pre-bronchodilator FEV1 and anFEV1/FVC ratio of < 0.70.

8. Current or former smokers with a history of at least 10 pack-years of tobaccosmoking

9. pack-year = 20 cigarettes smoked per day for one year). 9 Participants who arewilling and, in the opinion of the Investigator, able to adjust current COPDtherapy, as required by the protocol. Sex and Contraceptive/Barrier Requirements 10Females must not be of childbearing potential or must use a form of highly effectivebirth control as defined below:

• Females not of childbearing potential are defined as females who are eitherpermanently sterilised (hysterectomy, bilateral oophorectomy, or bilateralsalpingectomy) or postmenopausal. Females will be considered postmenopausal ifthey have been amenorrhoeic for 52 weeks (12 months) prior to the planned dateof randomisation without an alternative medical cause. The followingage-specific requirements apply:

• Females < 50 years old would be considered postmenopausal if they havebeen amenorrhoeic for 52 weeks (12 months) or more following cessation ofexogenous hormonal treatment with FSH levels in the postmenopausal range.

• Females ≥ 50 years old would be considered postmenopausal if they havebeen amenorrhoeic for 52 weeks (12 months) or more following cessation ofall exogenous hormonal treatment.

• Female participants of childbearing potential must use one highly effectiveform of birth control. A highly effective method of contraception is defined asone that can achieve a failure rate of less than 1% per year when usedconsistently and correctly. All FOCBP who are sexually active with a non-sterilised male partner must agree touse one highly effective method of birth control, as defined below, from enrolmentthroughout the study and until at least 14 days after the last dose of studyintervention. Cessation of contraception after this point should be discussed with aresponsible physician. Periodic abstinence (calendar, symptothermal, post-ovulationmethods), withdrawal (coitus interruptus), spermicides only, and lactational [15:32] Łubian, Dominika amenorrhoea method are not acceptable methods of contraception.Female condom and male condom should not be used together.

• All FOCBP must have a negative serum pregnancy test result at Visit 1.

• Females < 50 years of age with amenorrhoea for at least 12 months without analternative medical cause must have a serum FSH test at Visit 1.

• Highly effective birth control methods are listed below:

• Total sexual abstinence is an acceptable method provided it is thepreferred and usual lifestyle of the participant (defined as refrainingfrom heterosexual intercourse during the entire period of risk associatedwith the study interventions).

• Combined (oestrogen and progestogen-containing) hormonal contraceptionassociated with inhibition of ovulation:o Oralo Intravaginalo Transdermal

• Progestogen-only hormonal contraception associated with inhibition ofovulation: o Oral o Injectable

• Implantable

• Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)

• Bilateral tubal occlusion

• Male partner sterilisation/vasectomy with documentation of azoospermiaprior to the female participant's entry into the study, and this male isthe sole partner for that participant. The documentation on male sterilitycan come from the site personnel's review of participant's medicalrecords, medical examination and/or semen analysis or medical historyinterview provided by her or her partner. Informed Consent 11 Capable ofgiving signed informed consent as described in Appendix A which includescompliance with the requirements and restrictions listed in the ICF and inthis protocol. Other Inclusion Criteria 12 Participants with calculated eGFR > 30 mL/min/1.73 m2using the CKD-EPI formula.

13 Participants who demonstrate acceptable MDI administration and spirometry techniques.

14 Participants who remain compliant with placebo run-in administrations, defined as ≥ 80% of planned doses over the last 7 days prior to Visit 3, based on ePRO diary data.

15 Participants who are willing to remain at the study centre as required per protocol to complete all visit assessments.

Exclusion Criteria:

Medical Conditions

1. Confirmed diagnosis of asthma, in the opinion of the Investigator based on thoroughreview of medical history and medical records.

2. COPD due to α1-antitrypsin deficiency.

3. A COPD exacerbation treated with systemic corticosteroids or antibiotics within 4months prior to Visit 1 or during the Screening Period.

4. A COPD exacerbation that required hospitalisation within 12 months prior to Visit 1or during the Screening Period.

5. A respiratory infection ending within 4 weeks prior to Visit 1 or beginning orending during the Screening Period, per the Investigator's judgement.

6. Life-threatening COPD (eg, need for mechanical ventilation) at any time prior toVisit 1 or during the Screening Period.

7. A SARS-CoV-2 infection in the 8 weeks prior to Visit 1 or during the ScreeningPeriod, or that required hospitalisation at any time prior to Visit 1 or during theScreening Period.

8. Sleep apnoea that, in the opinion of the Investigator, is uncontrolled.

9. Other respiratory disorders including, but not limited to, known activetuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis (high-resolution CT evidence of bronchiectasis that causes repeated acuteexacerbations), severe neurological disorders affecting control of the upper airway,sarcoidosis, primary ciliary dyskinesia, idiopathic interstitial pulmonary fibrosis,primary pulmonary hypertension, or pulmonary thromboembolic disease.

10. Significant or unstable ischaemic heart disease, arrhythmia, cardiomyopathy, heartfailure, uncontrolled hypertension as defined by the Investigator, or any otherrelevant cardiovascular disorder as judged by the Investigator.

11. Diagnosis of narrow-angle glaucoma that has not been adequately treated, or a changein vision that may be relevant, in the opinion of the Investigator. Note: All medications approved for control of intraocular pressures are allowed,including topical ophthalmic nonselective beta-blockers and prostaglandin analogues.

12. Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retentionthat, in the opinion of the Investigator, is clinically significant.

13. Unresectable cancer that has not been in complete remission for at least 5 yearsprior to Visit 1. Note: Squamous cell and basal cell carcinomas of the skin areallowed.

14. Historical or current evidence of a clinically significant disease including, butnot limited to: cardiovascular, hepatic, renal, haematological, neurological,endocrine, gastrointestinal, or pulmonary. Immune deficiency disorders (ie, HIVinfection) should be excluded even if controlled. Significant is defined as anydisease that, in the opinion of the Investigator, would put the safety of theparticipant at risk through participation, or that could affect the efficacy orsafety analysis if the disease/condition is exacerbated during the study.

15. Participants with a known hypersensitivity to beta2-agonists, muscarinicantagonists, or corticosteroids, or any component of the MDI.

16. Known history of drug or alcohol abuse within 12 months of Visit 1 or known abuse atany time during the study.

17. History of QT prolongation associated with another medication that requireddiscontinuation of that medication. Prior/Concomitant Therapy

18. Unable to abstain from short-acting bronchodilators within 6 hours prior to lungfunction testing at each study visit.

19. Pulmonary resection or lung volume reduction surgery during the 6 months prior toVisit 1 (ie, lobectomy, bronchoscopic lung volume reduction [endobronchial blockers,airway bypass, endobronchial valves, thermal vapour ablation, biological sealants,and airway implants]).

20. Long-term-oxygen therapy or nocturnal oxygen therapy required for greater than 15hours per day. Note: As-needed oxygen use is allowed.

21. Trans-urethral resection of the prostate or full resection of the prostate within 6months prior to Visit 1.

22. Unable to abstain from any protocol-defined prohibited medications during theScreening or Treatment Periods (see Section 6.9).

23. Use of any herbal products by either inhalation or nebuliser within 2 weeks prior toVisit 1 or refusal to stop use for the duration of the study. Prior/Concurrent Clinical Study Experience

24. Participation in another clinical study with a study intervention administeredwithin 30 days or 5 half-lives, whichever is longer, prior to Visit 1. Diagnostic Assessments

25. Participants with ECG QTcF interval > 480 milliseconds.

26. Participants with high-degree atrioventricular block II or III, or with sinus nodedysfunction with clinically significant pauses who are not treated with pacemaker.

27. Any clinically relevant abnormal findings in physical examination, clinicalchemistry, haematology, urinalysis, vital signs, or ECG which, in the opinion of theInvestigator, may put the participant at risk because of their participation in thestudy. Other Exclusions

28. Planned hospitalisation during the study.

29. Involvement in the planning or conduct of the study (applies to both AstraZenecastaff and staff at the study sites).

30. Study Investigators, sub-Investigators, coordinators, and their employees orimmediate family members.

31. Judgement by the Investigator that the participant should not participate in thestudy if the participant is unlikely to comply with study procedures, restrictions,and requirements.

32. Previous randomisation in the present study.

33. For women only: currently pregnant (confirmed with positive pregnancy test),breastfeeding, or planned pregnancy during the study, or FOCBP not using acceptablecontraception measures.