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

Recruiting at 66 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: ICS/LABA, LAMA/LABA

Must not be taking: Herbal products

Disqualifiers: Asthma, Sleep apnea, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

558 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares the safety of two inhalers for people with moderate to very severe COPD. One inhaler uses a new type of propellant, while the other uses a traditional one. Both inhalers deliver medicine directly to the lungs to help patients breathe easier. Previous studies have compared the new inhaler with traditional ones.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that participants must be willing to adjust their COPD therapy as required by the protocol. It also states that you must abstain from certain prohibited medications during the study.

What data supports the effectiveness of the drug Symbicort (budesonide/formoterol)?

Research shows that Symbicort, which combines budesonide and formoterol, is effective in reducing asthma exacerbations and provides rapid relief for acute asthma. It is also comparable in effectiveness to other combination therapies like fluticasone/formoterol. ^{1 2 3 4 5}

Is budesonide safe for children with asthma?

In a study of children with asthma, budesonide inhalation suspension was found to be generally safe, with similar rates of mild adverse events (like fever and injection-site reactions) compared to other asthma treatments. ^{6 7 8 9 10}

What makes the drug Budesonide/Formoterol/Glycopyrronium unique for treating COPD?

This drug combines three components—budesonide, glycopyrronium, and formoterol—into a single inhaler, offering a convenient option for COPD maintenance. It uses co-suspension delivery technology to improve lung function and reduce exacerbations more effectively than dual therapies, while also enhancing quality of life and reducing mortality risk. ^{1 2 4 5 11}

Eligibility Criteria

Inclusion Criteria

You have been using specific types of inhalers to manage your COPD for at least 6 weeks before the study.

Participant must be 40 to 80 years of age inclusive, at the time of signing the ICF

Participants willing and able to adjust current COPD therapy, as required by the protocol

Exclusion Criteria

Participants with a documented history of physician-diagnosed asthma within 5 years of Visit 1

Participants with COPD due to α1-Antitrypsin Deficiency

Pulmonary resection or lung volume reduction surgery during the 26 weeks (6 months) prior to Visit 1

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BGF MDI HFO or BGF MDI HFA twice daily for 12 weeks

12 weeks

Extension

A subset of participants continue treatment for an additional 40 weeks

40 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Budesonide
• Formoterol Fumarate
• Glycopyrronium

Participant Groups

Group I: BGF MDI HFO 320/14.4/9.6μg Experimental Treatment 1 Intervention

Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) Delivered by MDI HFO (HFO-1234ze)

Group II: BGF MDI HFA 320/14.4/9.6 μg Active Control 1 Intervention

Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) Delivered by MDI HFA

Budesonide is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Pulmicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis
• Crohn's disease
• Ulcerative colitis
• Microscopic colitis
• Eosinophilic esophagitis
• Primary immunoglobulin A nephropathy

Approved in United States as Entocort EC for:

• Crohn's disease
• Ulcerative colitis
• Primary immunoglobulin A nephropathy
• Eosinophilic esophagitis

Approved in Canada as Pulmicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a Phase 3 study involving 279 patients with moderate to severe asthma, fluticasone/formoterol was found to be as effective as budesonide/formoterol in improving lung function, measured by the change in pre-dose FEV₁ over 12 weeks.

Both treatments demonstrated a similar safety profile, indicating that fluticasone/formoterol is a viable alternative to budesonide/formoterol for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluticasone/formoterol combination therapy versus budesonide/formoterol for the treatment of asthma: a randomized, controlled, non-inferiority trial of efficacy and safety. Bodzenta-Lukaszyk, A., Buhl, R., Balint, B., et al.[2015]

In a study of 373 patients with moderate persistent asthma, Symbicort (budesonide/formoterol) significantly improved lung function compared to fluticasone propionate, with greater increases in morning peak expiratory flow (PEF) and fewer asthma exacerbations.

Symbicort also led to better overall asthma control, as indicated by a higher percentage of symptom-free days and reduced reliance on reliever medication, while both treatments were well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with single inhaler budesonide/formoterol compared with high dose of fluticasone propionate alone in patients with moderate persistent asthma. Bateman, ED., Bantje, TA., João Gomes, M., et al.[2019]

Symbicort, a combination inhaler for asthma and COPD, is more cost-effective than using separate inhalers for its components, budesonide and formoterol, as it leads to lower total treatment costs.

The adjustable dosing strategy of Symbicort not only maintains better asthma control with less medication but also reduces overall treatment costs compared to fixed dosing and other combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symbicort: a pharmacoeconomic review. Halpin, DM.[2018]

In a long-term safety trial involving 896 patients with rheumatoid arthritis, tacrolimus at a dose of 3 mg/day was found to be safe and well-tolerated over a median treatment duration of 359 days, with no new adverse events appearing after the first 3 months.

The treatment resulted in significant clinical benefits, with ACR20, ACR50, and ACR70 response rates of 38.4%, 18.6%, and 9.0% respectively, indicating that over 26% of patients experienced at least a 70% improvement in joint symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of tacrolimus in patients with rheumatoid arthritis: long-term experience. Yocum, DE., Furst, DE., Bensen, WG., et al.[2019]

Converting stable liver transplant patients from once-daily prolonged-release tacrolimus to once-daily extended-release tacrolimus is safe, with only two patients experiencing adverse effects that resolved after returning to the original medication.

This conversion not only reduced the mean daily cost of tacrolimus therapy from 5.54 to 4.11 Euros per patient but also required careful monitoring and dose adjustments to maintain effective serum levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conversion From Once-Daily Prolonged-Release Tacrolimus to Once-Daily Extended-Release Tacrolimus in Stable Liver Transplant Recipients. Altieri, M., Delaval, G., Kimmoun, E., et al.[2018]

Etanercept, the first biological disease-modifying antirheumatic drug approved over 15 years ago, effectively reduces symptoms and improves quality of life in patients with various rheumatic diseases, including rheumatoid arthritis and psoriatic arthritis, with benefits sustained during long-term treatment.

The safety profile of etanercept is consistent with its approved labeling, showing manageable adverse events, making it a cost-effective and central treatment option for autoimmune rheumatic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept: a review of its use in autoimmune inflammatory diseases. Scott, LJ.[2022]

In pivotal phase III trials lasting 24-52 weeks, the combination of budesonide, glycopyrronium, and formoterol significantly reduced moderate to severe COPD exacerbations and improved lung function compared to other combinations.

This inhaler was well tolerated and not only improved symptoms like dyspnoea and quality of life but also reduced the risk of all-cause mortality, making it a strong option for patients with inadequately controlled COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide/Glycopyrronium/Formoterol: A Review in COPD. Heo, YA.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Fluticasone/formoterol combination therapy versus budesonide/formoterol for the treatment of asthma: a randomized, controlled, non-inferiority trial of efficacy and safety. [2015]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Combination therapy with single inhaler budesonide/formoterol compared with high dose of fluticasone propionate alone in patients with moderate persistent asthma. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Inhibitory effect of budesonide alone and in combination with formoterol on IL-5 and RANTES production from mononuclear cells. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Symbicort: a pharmacoeconomic review. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Budesonide/formoterol and formoterol provide similar rapid relief in patients with acute asthma showing refractoriness to salbutamol. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Safety of tacrolimus in patients with rheumatoid arthritis: long-term experience. [2019]

7. India pubmed.ncbi.nlm.nih.gov

Antibody response after varicella vaccination in children treated with budesonide inhalation suspension or non-steroidal conventional asthma therapy. [2006]

8. Turkey pubmed.ncbi.nlm.nih.gov

Conversion From Once-Daily Prolonged-Release Tacrolimus to Once-Daily Extended-Release Tacrolimus in Stable Liver Transplant Recipients. [2018]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Etanercept: a review of its use in autoimmune inflammatory diseases. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Comparison of three tacrolimus-based immunosuppressive regimens in lung transplantation. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Budesonide/Glycopyrronium/Formoterol: A Review in COPD. [2022]