A Study to Assess the Safety of Budesonide/Glycopyrronium/Formoterol Fumarate With a Next-Generation Propellant in Participants With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Inclusion Criteria: 1. Participant must be 40 to 80 years of age inclusive, at the time of signing the ICF; 2. Participants who have a documented history of physician-diagnosed COPD as defined by the ATS/ERS (Celli et al 2004) or by locally applicable guidelines; 3. Participants who have been regularly using dual ICS/LABA, LAMA/LABA, or ICS/LAMA/LABA (open or fixed-dose combinations) inhaled maintenance therapies for the management of their COPD for at least 6 weeks prior to Screening; 4. Participants who have pre-bronchodilator FEV1 of \< 80% predicted normal at Visit 1; 5. Participants who have post-bronchodilator FEV1/FVC ratio of \< 0.70 and post-bronchodilator FEV1 of ≥ 25% to \< 80% predicted normal at Visit 2; 6. Participants who have CAT score ≥ 10 at Visit 1; 7. Participants who are current/former smokers with a history of at least 10 pack-years of tobacco smoking (1 pack year = 20 cigarettes smoked per day for 1 year); 8. Participants who are willing and, in the opinion of the Investigator, able to adjust current COPD therapy, as required by the protocol; 9. Participants must be able to demonstrate acceptable MDI administration and spirometry technique; 10. Participants who are willing to remain at the study center as required per protocol to complete all visit assessments; 11. Females must either be not of childbearing potential, or using a form of highly effective birth control as defined below: * Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 52 weeks (12 months) prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply: * Women \< 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 and follicle stimulating hormone levels in the postmenopausal range. * Women ≥ 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. 12. 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. At enrollment, women of childbearing potential who are sexually active with a non-sterilized male partner should be stable on their chosen method of highly effective birth control, as defined below, and willing to remain on the birth control until at least 14 days after 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 amenorrhea method are not acceptable methods of contraception. Female condom and male condom should not be used together. * All women of childbearing potential must have a negative serum pregnancy test result at Visit 1 * Women \<50 years of age with amenorrhea for 12 months without an alternative medical cause must have a serum LH and FSH test (within 21-28 days before Visit 3) for study eligibility Highly effective birth control methods are listed below: * Sexual abstinence defined as complete abstinence from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: * Oral * Intravaginal * Transdermal * Progestogen-only hormonal contraception associated with inhibition of ovulation: * Oral * Injectable * Implantable * Intrauterine device or intrauterine hormone-releasing system * Male partner sterilization/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. * Bilateral tubal ligation 13. 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 Exclusion Criteria: 1. Participants who have a documented history of physician-diagnosed asthma in the opinion of the Investigator based on thorough review of medical history and medical records, within 5 years of Visit 1; 2. Participants who have COPD due to α1-Antitrypsin Deficiency; 3. Participants with historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary. Significant is defined as any uncontrolled disease or 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 analyses; 4. Sleep apnea that, in the opinion of the Investigator, cannot be controlled; 5. Other respiratory disorders including known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis (high resolution CT evidence of bronchiectasis that causes repeated acute exacerbations), immune deficiency disorders, severe neurological disorders affecting control of the upper airway, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or pulmonary thromboembolic disease; 6. Participant with moderate or severe COPD exacerbation or respiratory infection ending within 4 weeks prior to Visit 1 or during the Screening period; 7. Participant who has had a SARS-CoV-2 infection in the 8 weeks prior to Visit 1 or during the Screening Period or that required hospitalization at any time prior to Visit 1 or during the Screening Period; 8. Pulmonary resection or lung volume reduction surgery during the 26 weeks (6 months) prior to Visit 1 (ie, lobectomy, bronchoscopy lung volume reduction \[endobronchial blockers, airway bypass, endobronchial valves, thermal vapor ablation, biological sealants, and airway implants\]); 9. Long-term oxygen therapy; 10. Imminent life-threatening COPD (eg, need for mechanical ventilation); 11. Participant who has significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator; 12. Participant with narrow angle glaucoma not adequately treated and/or 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 analogs. 13. Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the Investigator, is clinically significant; Note: Participants with trans-urethral resection of prostate or full resection of the prostate within 26 weeks (6 months) prior to Visit 1 are excluded from the study 14. 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 not exclusionary 15. Known history of drug or alcohol abuse within 52 weeks (12 months) of Visit 1; 16. Unable to withhold short-acting bronchodilators for 6 hours prior to lung function testing at each applicable study visit; 17. Participant is unable to abstain from protocol-defined prohibited medications during Screening and Treatment Periods; 18. Using any herbal products either by inhalation or nebulizer within 2 weeks of Visit 1 and does not agree to stop for the duration of the study; 19. Participants with a known hypersensitivity to beta2-agonists, muscarinic antagonists, or corticosteroids, or any component of the MDI; 20. Participation in another clinical study with an intervention administered in the last 30 days or 5 half-lives, whichever is longer; 21. Previous randomization in any study using BGF MDI HFO (budesonide/glycopyrronium/formoterol fumarate - HFO); 22. Participants with calculated eGFR ≤ 30 mL/minute/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula; 23. Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, vital signs, or ECG, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study; Note: Participants with ECG QTcF interval (corrected for heart rate using Fridericia's formula \[QTcF\]) \> 480 msec will be excluded. Participants with high degree atrioventricular block II or III, or with sinus node dysfunction with clinically significant pauses who are not treated with pacemaker will also be excluded. 24. Planned hospitalization during the study; 25. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site); 26. Study Investigators, sub-Investigators, coordinators, and their employee or immediate family members; 27. Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions and requirements; 28. For women only - currently pregnant (confirmed with positive pregnancy test), breast feeding, or planned pregnancy during the study or women of childbearing potential not using acceptable contraception measures (see Inclusion criterion 12 in Section 5.1).