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 Participants must be 40 to 80 years inclusive at the time of signing the ICF. Type of Participant and Disease Characteristics Participants who have a documented history of physician-diagnosed COPD as defined by the ATS/ERS (Celli et al 2004). Participants who have been receiving LABA, LAMA, LAMA/LABA, or ICS/LABA inhaled maintenance therapies for the management of their COPD for at least 4 weeks prior to Visit 1, OR Participants who have been receiving SABA, SAMA, or SABA/SAMA either scheduled or as needed for at least 4 weeks prior to Visit 1, OR Participants who are COPD treatment-naïve or have not received previously prescribed COPD treatment in the 4 weeks prior to Visit 1. At Visit 1: Participants with a blood eosinophil count < 300 cells/μL. At Visit 1: Participants with a pre-bronchodilator FEV1 of < 80% predicted normal. At Visit 2: Participants with a post-bronchodilator FEV1/FVC ratio of < 0.70 and a postbronchodilator FEV1 of ≥ 40% to < 80% predicted normal. At Visit 3 (TP 1 Day 1): Participants with a pre-dose FEV1 of < 80% predicted normal that is within ± 20% or 200 mL of their Visit 2 pre-bronchodilator FEV1 and an FEV1/FVC ratio of < 0.70. Current or former smokers with a history of at least 10 pack-years of tobacco smoking pack-year = 20 cigarettes smoked per day for one year). 9 Participants who are willing and, in the opinion of the Investigator, able to adjust current COPD therapy, as required by the protocol. Sex and Contraceptive/Barrier Requirements 10 Females must not be of childbearing potential or must use a form of highly effective birth control as defined below: Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal. Females will be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) prior to the planned date of randomisation without an alternative medical cause. The following age-specific requirements apply: Females < 50 years old would be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) or more following cessation of exogenous hormonal treatment with FSH levels in the postmenopausal range. Females ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) or more following cessation of all exogenous hormonal treatment. Female participants of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. All FOCBP who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, from enrolment throughout the study and until at least 14 days after the last dose of study intervention. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence (calendar, symptothermal, post-ovulation methods), 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 an alternative 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 the preferred and usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study interventions). - Combined (oestrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation: o Oral o Intravaginal o Transdermal Progestogen-only hormonal contraception associated with inhibition of ovulation: o Oral o Injectable Implantable Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) Bilateral tubal occlusion Male partner sterilisation/vasectomy with documentation of azoospermia prior to the female participant's entry into the study, and this male is the sole partner for that participant. The documentation on male sterility can come from the site personnel's review of participant's medical records, medical examination and/or semen analysis or medical history interview provided by her or her partner. Informed Consent 11 Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Other Inclusion Criteria 12 Participants with calculated eGFR > 30 mL/min/1.73 m2 using 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 Confirmed diagnosis of asthma, in the opinion of the Investigator based on thorough review of medical history and medical records. COPD due to α1-antitrypsin deficiency. A COPD exacerbation treated with systemic corticosteroids or antibiotics within 4 months prior to Visit 1 or during the Screening Period. A COPD exacerbation that required hospitalisation within 12 months prior to Visit 1 or during the Screening Period. A respiratory infection ending within 4 weeks prior to Visit 1 or beginning or ending during the Screening Period, per the Investigator's judgement. Life-threatening COPD (eg, need for mechanical ventilation) at any time prior to Visit 1 or during the Screening Period. A SARS-CoV-2 infection in the 8 weeks prior to Visit 1 or during the Screening Period, or that required hospitalisation at any time prior to Visit 1 or during the Screening Period. Sleep apnoea that, in the opinion of the Investigator, is uncontrolled. Other respiratory disorders including, but not limited to, known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis (high-resolution CT evidence of bronchiectasis that causes repeated acute exacerbations), severe neurological disorders affecting control of the upper airway, sarcoidosis, primary ciliary dyskinesia, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or pulmonary thromboembolic disease. Significant or unstable ischaemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator. Diagnosis of narrow-angle glaucoma that has not been adequately treated, or a change in 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. Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the Investigator, is clinically significant. Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1. Note: Squamous cell and basal cell carcinomas of the skin are allowed. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, haematological, neurological, endocrine, gastrointestinal, or pulmonary. Immune deficiency disorders (ie, HIV infection) should be excluded even if controlled. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or that could affect the efficacy or safety analysis if the disease/condition is exacerbated during the study. Participants with a known hypersensitivity to beta2-agonists, muscarinic antagonists, or corticosteroids, or any component of the MDI. Known history of drug or alcohol abuse within 12 months of Visit 1 or known abuse at any time during the study. History of QT prolongation associated with another medication that required discontinuation of that medication. Prior/Concomitant Therapy Unable to abstain from short-acting bronchodilators within 6 hours prior to lung function testing at each study visit. Pulmonary resection or lung volume reduction surgery during the 6 months prior to Visit 1 (ie, lobectomy, bronchoscopic lung volume reduction [endobronchial blockers, airway bypass, endobronchial valves, thermal vapour ablation, biological sealants, and airway implants]). Long-term-oxygen therapy or nocturnal oxygen therapy required for greater than 15 hours per day. Note: As-needed oxygen use is allowed. Trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to Visit 1. Unable to abstain from any protocol-defined prohibited medications during the Screening or Treatment Periods (see Section 6.9). Use of any herbal products by either inhalation or nebuliser within 2 weeks prior to Visit 1 or refusal to stop use for the duration of the study. Prior/Concurrent Clinical Study Experience Participation in another clinical study with a study intervention administered within 30 days or 5 half-lives, whichever is longer, prior to Visit 1. Diagnostic Assessments Participants with ECG QTcF interval > 480 milliseconds. Participants with high-degree atrioventricular block II or III, or with sinus node dysfunction with clinically significant pauses who are not treated with pacemaker. Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, or ECG which, in the opinion of the Investigator, may put the participant at risk because of their participation in the study. Other Exclusions Planned hospitalisation during the study. Involvement in the planning or conduct of the study (applies to both AstraZeneca staff and staff at the study sites). Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members. Judgement 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 randomisation in the present study. For women only: currently pregnant (confirmed with positive pregnancy test), breastfeeding, or planned pregnancy during the study, or FOCBP not using acceptable contraception measures.