Budesonide/Glycopyrronium/Formoterol for COPD

No longer recruiting at 78 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of a new inhaler using Budesonide (a corticosteroid), Glycopyrronium, and Formoterol Fumarate for individuals with moderate to very severe COPD, a lung disease that makes breathing difficult. Researchers are comparing two inhalers that deliver the same medication but use different propellants. The trial seeks participants diagnosed with COPD who experience frequent breathing difficulties and are current or former smokers with a history of smoking. Those who have used inhaler therapies for COPD for at least six weeks might be a good fit for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to advancing COPD treatment options.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that using a combination of three medications—budesonide, glycopyrronium, and formoterol fumarate—in different inhalers is generally safe for people with COPD, a lung disease that makes breathing difficult. Research on a new propellant, HFO-1234ze, indicates it is as safe as the older one, HFA-134a.

Trials have tested both versions, and results show similar side effects. These side effects are mostly mild to moderate, such as headaches, sore throat, or cough. Importantly, the FDA has approved these medications for other uses, confirming their safety.

Overall, evidence suggests these treatments are well-tolerated, with manageable side effects. This information can help prospective clinical trial participants understand what to expect regarding safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about these treatments for chronic obstructive pulmonary disease (COPD) because they explore a new propellant system. The combination of Budesonide, Glycopyrronium, and Formoterol Fumarate is being delivered using a hydrofluoroolefin (HFO) propellant, which is more environmentally friendly compared to the traditional hydrofluoroalkane (HFA) propellant. This innovation in delivery method could lead to reduced environmental impact without compromising the effectiveness of the medication. Additionally, the combination of these three active ingredients targets inflammation, airway constriction, and mucus production, potentially offering comprehensive control of COPD symptoms.

What evidence suggests that this trial's treatments could be effective for COPD?

Research has shown that the combination of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) effectively treats COPD. This trial will compare two delivery methods of BGF: MDI HFO and MDI HFA. Studies have found that BGF significantly improves lung function and quality of life for people with moderate to severe COPD. It enhances scores on tests measuring symptoms and the disease's impact on daily life, such as the COPD Assessment Test (CAT) and the St. George's Respiratory Questionnaire (SGRQ). Patients using BGF reported fewer serious lung-related problems. These findings suggest that BGF could be a valuable treatment option for those living with COPD. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Budesonide
• Formoterol Fumarate
• Glycopyrronium

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40513294/

EBISU study Triple therapy with a BGF MDI significantly improved CAT and SGRQ scores over 12 weeks. BGF MDI could be a suitable option for patients living with COPD.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2212534525000711

Real-world effectiveness of budesonide/glycopyrronium/ ... Triple therapy with a BGF MDI significantly improved CAT and SGRQ scores over 12 weeks. BGF MDI could be a suitable option for patients living with COPD.

3. publications.ersnet.org publications.ersnet.org/content/erj/64/suppl68/pa3909

Real-world outcomes of Budesonide/Glycopyrronium ... RECORD is an observational single arm cohort study investigating effectiveness of Budesonide/Glycopyrronium/Formoterol (BGF) therapy in COPD patients.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1544319125005850

Safety and efficacy of budesonide/glycopyrrolate/formoterol ... The current study demonstrated that BGF significantly improved lung function compared with GFF in individuals with moderate to severe COPD at ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38813078/

Real-World Use and Early Medication Success The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12359160/

Safety of budesonide/glycopyrronium/formoterol fumarate ... This study assessed the safety of a near-zero GWP propellant, hydrofluoroolefin-1234ze (HFO-1234ze), compared with HFA-134a when used in the ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05573464

NCT05573464 | A Study to Assess the Safety of ... This is a Phase 3 randomized, double-blind, 12-week (with an extension to 52 weeks in a subset of participants) study comparing the safety of BGF MDI HFO ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/212122s000lbl.pdf

Breztri Aerosphere - accessdata.fda.gov Inhalation Aerosol: a pressurized metered dose inhaler that delivers a combination of 160 mcg budesonide, 9 mcg glycopyrrolate, and 4.8 mcg formoterol fumarate ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40831469/

Safety of budesonide/glycopyrronium/formoterol fumarate ... Safety of budesonide/glycopyrronium/formoterol fumarate dihydrate delivered by HFO-1234ze versus HFA-134a in chronic obstructive pulmonary ...

10. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D5985C00003

A Study to Assess the Safety of Budesonide ... This is a 12-week (with an extension to 52 weeks in a subset of participants) study comparing the safety of BGF MDI HFO twice daily (BID) with BGF MDI HFA ...