| Eligibility |
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 a1-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).
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