A Study to Evaluate the Effect of BGF MDI, BFF MDI and Placebo MDI on Exercise Parameters in Participants with COPD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

19 Oct 2023 → 22 Jan 2026

Decision date (initial)

2023-09-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the effect of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) metered dose inhaler (MDI) relative to Placebo metered dose inhaler (MDI) and Budesonide and Formoterol Fumarate (BFF) metered dose inhaler (MDI) on dynamic hyperinflation in participants with Chronic obstructive pulmonary disease (COPD).

Secondary objectives 5

1. To assess the effect of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) metered dose inhaler (MDI) relative to Placebo metered dose inhaler (MDI) and Budesonide and Formoterol Fumarate (BFF) metered dose inhaler (MDI) on exercise endurance time in participants with Chronic obstructive pulmonary disease (COPD).
2. To assess the effect of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) metered dose inhaler (MDI) relative to Placebo metered dose inhaler (MDI) on isotime dyspnea in participants with Chronic obstructive pulmonary disease (COPD).
3. To assess the effect of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) metered dose inhaler (MDI) relative to Budesonide and Formoterol Fumarate (BFF) metered dose inhaler (MDI), in participants with Chronic obstructive pulmonary disease (COPD), on the following: Isotime dyspnea; and Static lung volumes.
4. To assess the effect of Budesonide and Formoterol Fumarate (BFF) metered dose inhaler (MDI) relative to Placebo, in participants with Chronic obstructive pulmonary disease (COPD), on the following: Exercise endurance time; Isotime dyspnea and Static lung volumes.
5. To assess the safety and tolerability of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) metered dose inhaler (MDI) and Budesonide and Formoterol Fumarate (BFF) metered dose inhaler (MDI).

Conditions and MedDRA coding

Chronic Obstructive Pulmonary Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female, 40 to 80 years of age inclusive, at the time of signing the informed consent.
2. Participant must have: (a) A diagnosis of Chronic obstructive pulmonary disease (COPD) confirmed by a post-bronchodilator Forced Expiratory Volume in 1 second/Forced Vital Capacity (FEV1/FVC) < 0.7 at Visit 1. (b) A post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) ≥ 30% and < 80% predicted normal (moderate to severe Chronic obstructive pulmonary disease (COPD)) at Visit 1. (c) A score of ≥ 2 on the modified Medical Research Council (mMRC) at Visit 1. (d) Pre-bronchodilator Functional Residual Capacity (FRC) of > 120% of predicted normal FRC values at Visit 1.
3. Participant must be on mono- or dual inhaled maintenance Chronic Obstructive Pulmonary Disease (COPD) treatment at a stable dose for 6 weeks (Long-Acting Muscarinic Antagonist (LAMA), Long-Acting Beta2-Agonist (LABA), Long-Acting Muscarinic Antagonist/ Long-Acting Beta2- Agonist (LAMA/LABA), or Inhaled Corticosteroid/ Long- Acting Beta2-Agonist (ICS/LABA)).
4. Current or former smoker with a history of ≥ 10 pack-years of tobacco smoking.
5. Willing and, in the opinion of the investigator, able to adjust current Chronic Obstructive Pulmonary Disease (COPD) therapy, as required by the protocol (including Placebo periods).
6. Willing to visit at the study site as required per protocol to complete all visit assessments.
7. A Body Mass Index (BMI) < 40 kg/m2 .
8. A female is eligible to enter and participate in the study if the female is of: (a) Non-childbearing potential: either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. A female will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply: (i) Female < 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle-stimulating hormone levels in the postmenopausal range. (ii) Female ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment. (b) Childbearing potential, has a negative serum pregnancy test at Visit 1 and 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. (c) Highly effective birth control methods include: - Sexual abstinence as defined as complete abstinence from intercourse when it is the preferred and usual lifestyle of the participant (however, periodic abstinence eg, calendar, ovulation, symptothermal, post-ovulation methods, declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception). - Contraceptive subdermal implant. - Intrauterine device or intrauterine system. - Oral contraceptive (combined or progesterone only). - Injectable progestogen. - Contraceptive vaginal ring. - Percutaneous contraceptive patches. - Male partner sterilization 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 study 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
9. Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in the protocol.

Exclusion criteria 25

1. A current diagnosis of asthma, asthma-Chronic Obstructive Pulmonary Disease (COPD)-overlap, or any other chronic respiratory disease other than Chronic Obstructive Pulmonary Disease (COPD) such as alpha-1 antitrypsin deficiency, active tuberculosis, lung cancer, lung fibrosis, sarcoidosis, interstitial lung disease and pulmonary hypertension.
2. 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 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.
3. Participants on oxygen therapy or that desaturate significantly (<82%) during exercise.
4. Participants who are enrolled or entering a pulmonary rehabilitation program during the study (from Visit 1 onwards). These participants will be allowed to re-screen after completion of the pulmonary rehabilitation program.
5. Participants who have cancer that has not been in complete remission for at least 5 years. Note: Participants with squamous cell carcinoma of the skin, basal cell carcinoma of the skin in complete remission for 1 year are allowed in the study.
6. Participants with a diagnosis of narrow-angle glaucoma that has not been adequately treated and/or change in vision that may be relevant, in the opinion of the investigator. All medications approved for control of intraocular pressures are allowed including topical ophthalmic non-selective beta-blockers and prostaglandin analogues.
7. Participants with 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 6 months prior to Visit 1 are excluded from the study.
8. Participants who have a history of hypersensitivity to β2-agonists, budesonide or any other corticosteroid components, glycopyrronium or other muscarinic anticholinergics, or any component of the metered dose inhaler (MDI) or dry powder inhaler.
9. Participant with resting (5 minutes) oxygen saturation SaO2 in room air ≤ 85%.
10. A Chronic Obstructive Pulmonary Disease (COPD) exacerbation that requires hospitalization within 12 months prior to Visit 1 or a COPD exacerbation that requires systemic corticosteroids or antibiotics within 4 months of Visit 1.
11. Participants with contraindications to cardiopulmonary exercise testing, including (but not limited to): (a) Acute myocardial infarction (within 6 months prior to Visit 1). (b) Unstable angina. (c) Uncontrolled arrhythmias, including atrial fibrillation with uncontrolled ventricular rate. (d) Active endocarditis. (e) Acute myocarditis or pericarditis. (f) Symptomatic aortic stenosis. (g) Uncontrolled heart failure. (h) Pulmonary embolism, uncontrolled pulmonary edema. (i) Acute non-cardiac disorder that may affect exercise performance or be aggravated by exercise (eg, infection, renal failure, thyrotoxicosis, acute bleeding, electrolyte abnormalities). (j) Left main coronary stenosis or equivalent. (k) Moderate or severe stenotic valvular cardiac disease. (l) Severe untreated arterial hypertension (> 200 mmHg systolic, > 120 mmHg diastolic). (m) Severe pulmonary hypertension. (n) Syncope tachyarrhythmias or bradyarrhythmias. (o) Hypertrophic cardiomyopathy. (p) Mental impairment leading to limited ability to perform study procedures. (q) High degree atrioventricular block. (r) Deep venous thrombosis of lower extremities. (s) Suspected dissecting aneurysm. (t) Participants with uncontrolled Type I diabetes mellitus.
12. Participants who have had a respiratory tract infection within 8 weeks prior to Visit 1 and/or during the screening period. . Participants who develop an upper or lower respiratory tract infection during the screening period will not be eligible, but will be permitted to be re-screened 8 weeks after the resolution of the respiratory tract infection.
13. Participants with lung lobectomy, lung volume reduction (during the study and within 3 months of Visit 1), or lung transplantation.
14. Unable to withhold short-acting bronchodilators for 6 hours prior to lung function testing at each study visit.
15. Unable to abstain from protocol-defined prohibited medications.
16. Participation in another clinical study with an investigational product 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 this protocol is prohibited for use during the duration of the study).
17. Participants with a known hypersensitivity to beta2-agonists, muscarinic antagonists, or corticosteroids, or any component of the metered dose inhaler (MDI).
18. Participants with estimated Glomerular Filtration Rate (eGFR) ≤ 30 mL/minute/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
19. Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, vital signs, or Electrocardiogram (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 Electrocardiogram QT Interval Corrected for Heart Rate (ECG QTcF) interval > 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.
20. Investigatory safety concerns regarding the participant’s enrollment.
21. Known history of drug or alcohol abuse within 12 months of Visit 1.
22. Any regular recreational use of marijuana in the 12 months prior to Visit 1 and throughout the study, as per investigator’s discretion.
23. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
24. 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.
25. Participants who have been previously randomized but subsequently withdrew from the study either by the investigator, sponsor, or self-withdrawal cannot be re-screened for the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Isotime Inspiratory Capacity (IC).

Secondary endpoints 5

1. Constant work rate cycle ergometry endurance time.
2. Isotime dyspnea: isotime dyspnea Numerical Rating Scale (NRS).
3. - Static lung volumes: Functional Residual Capacity (FRC), Total Lung Capacity (TLC), Residual Volume (RV), Residual Volume/ Total Lung Capacity (RV/TLC), specific airway conductance (sGaw), and Inspiratory Capacity (IC).
4. Exercise endurance time: constant work rate cycle ergometry endurance time.
5. - Adverse Events (Serious Adverse Events and Adverse Event Leading to Discontinuation of Study Intervention only) (AEs (SAEs and DAEs only)). - Vital signs.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 1

Locations

2 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

17 submissions — initial application plus substantial / non-substantial modifications