BGF with Different Propellants for COPD

No longer recruiting at 106 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: LABA, LAMA, ICS

Disqualifiers: Asthma, Tuberculosis, Lung cancer, 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

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two types of inhalers to determine their effectiveness in improving lung function for people with COPD, a lung disease that makes breathing difficult. Participants will use different inhalers, including BGF MDI HFA and BGF MDI HFO, each for about four weeks, and undergo lung function tests. People with COPD who have used certain inhaler treatments for at least four weeks, or those who have not received treatment recently, might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to the development of potentially new treatment options.

Will I have to stop taking my current medications?

The trial 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. You may need to discuss this with the study team to understand what adjustments might be necessary.

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

Research has shown that both BGF MDI HFA and BGF MDI HFO treatments have been tested for safety in people with COPD. In a large study with over 8,500 participants, the BGF MDI HFA treatment had a 4.2% chance of causing pneumonia, which is important to consider for those with COPD, as it might increase the risk of pneumonia.

Studies have compared the BGF MDI HFO treatment to the HFA version to assess its safety. These studies examined the use of a new propellant, HFO-1234ze, which helps spray the medicine and is better for the environment due to its minimal global warming impact.

Both treatments have been studied for their effects on lung function and symptoms, and they appear to help people breathe easier and reduce flare-ups. Approval for use in other countries indicates that they have met certain safety standards.

Overall, BGF treatments are generally well-tolerated, but like any medicine, they can have side effects. It is important to consult a doctor if there are any concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments under trial for COPD because they explore using different propellants in the BGF inhaler, which could offer significant improvements over existing inhalation treatments. Most current COPD treatments, like Advair and Symbicort, use HFA propellants, but this trial is testing both an HFA and a novel HFO propellant. This could mean better lung delivery and reduced environmental impact, as HFOs have a much lower global warming potential compared to HFAs. By optimizing the delivery of the medication, these new formulations might enhance the effectiveness of managing COPD symptoms, offering a potential step forward in both patient care and environmental responsibility.

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

Research has shown that BGF, a combination of three medications, helps treat COPD by improving breathing and reducing flare-ups. In this trial, participants will receive BGF delivered with either an HFA or an HFO propellant, or a placebo. Studies have found that BGF, when delivered with an HFA propellant, works as well as other similar treatments, helping patients manage their symptoms. BGF is approved in several countries for COPD treatment and is known as Breztri or Trixeo. The new version of BGF uses an HFO propellant, which is better for the environment. Early research suggests that switching to HFO does not reduce its effectiveness in improving lung function. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 40-80 with COPD who have smoked at least the equivalent of 10 pack-years. They must be able to perform proper inhaler and breathing test techniques, have a certain blood cell count and lung function level, and either not be able to bear children or use effective birth control. People can't join if they've had asthma, recent drug/alcohol abuse, certain heart conditions, other respiratory disorders, or are pregnant.

Inclusion Criteria

Your kidney function, as measured by a test called eGFR, needs to be above a certain level.

I am willing to stay at the study center as needed for all visits.

I am between 40 and 80 years old.

Exclusion Criteria

Judgement by the Investigator that the participant should not participate in the study

I have been diagnosed with narrow-angle glaucoma or have problems due to an enlarged prostate.

I will be staying in the hospital during the study.

Timeline for a Trial Participant

Screening and Placebo Run-in

Participants are screened for eligibility to participate in the trial

2 weeks

3 visits (in-person)

Treatment

Participants undergo three treatment periods of approximately 4 weeks each, receiving BGF MDI HFO, BGF MDI HFA, and Placebo MDI HFA in a randomized sequence

12 weeks

3 visits (in-person) every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

1 visit (telephone contact)

What Are the Treatments Tested in This Trial?

Interventions

• BGF MDI HFA 320/14.4/9.6 μg
• BGF MDI HFO 320/14.4/9.6μg
• Placebo MDI HFA

Trial Overview The study tests whether BGF medication using a new propellant (HFO) works as well as the approved version with an older propellant (HFA) in improving lung function for COPD patients. Participants will try both versions and a placebo during different periods over about 15-16 weeks while attending regular clinic visits.

How Is the Trial Designed?

Group I: Treatment Sequence 6 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions in the following sequence. Sequence 6: Placebo MDI HFA BGF MDI HFA 320/14.4/9.6 μg BGF MDI HFO 320/14.4/9.6 μg

Group II: Treatment Sequence 5 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) in the following sequence. Sequence 5: Placebo MDI HFA BGF MDI HFO 320/14.4/9.6 μg BGF MDI HFA 320/14.4/9.6 μg

Group III: Treatment Sequence 4 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) in the following sequence. Sequence 4: BGF MDI HFA 320/14.4/9.6 μg Placebo MDI HFA BGF MDI HFO 320/14.4/9.6 μg

Group IV: Treatment Sequence 3 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) in the following sequence. Sequence 3: BGF MDI HFA 320/14.4/9.6 μg BGF MDI HFO 320/14.4/9.6 μg Placebo MDI HFA

Group V: Treatment Sequence 2 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) in the following sequence. Sequence 2: BGF MDI HFO 320/14.4/9.6 μg Placebo MDI HFA BGF MDI HFA 320/14.4/9.6 μg

Group VI: Treatment Sequence 1 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) in the following sequence. Sequence 1: BGF MDI HFO 320/14.4/9.6 μg BGF MDI HFA 320/14.4/9.6 μg Placebo MDI HFA

BGF MDI HFA 320/14.4/9.6 μg is already approved in United States, European Union, Japan, China for the following indications:

Approved in United States as Breztri Aerosphere for:

• Chronic Obstructive Pulmonary Disease (COPD)

Approved in European Union as Trixeo Aerosphere for:

• Chronic Obstructive Pulmonary Disease (COPD)

Approved in Japan as Breztri Aerosphere for:

• Chronic Obstructive Pulmonary Disease (COPD)

Approved in China as Breztri Aerosphere for:

• Chronic Obstructive Pulmonary Disease (COPD)

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

The study involving 56 healthy subjects demonstrated that using a spacer with the BGF MDI triple therapy significantly improved drug delivery, especially for individuals with suboptimal inhalation techniques, leading to higher lung and systemic exposure of the medication.

The safety profile of BGF MDI was generally favorable, with only mild to moderate treatment-emergent adverse events reported, indicating that the therapy is well-tolerated among users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative Bioavailability of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Administered With and Without a Spacer: Results of a Phase I, Randomized, Crossover Trial in Healthy Adults. Dorinsky, P., DePetrillo, P., DeAngelis, K., et al.[2020]

In a 28-week extension study involving 416 Japanese patients with moderate-to-very severe COPD, the budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) demonstrated a safety profile comparable to other dual therapies, with similar rates of treatment-emergent adverse events (TEAEs) across all treatment groups.

The most common TEAEs were nasopharyngitis and bronchitis, with a low incidence of major adverse cardiovascular events and pneumonia, indicating that BGF MDI is well tolerated for long-term use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD. Ichinose, M., Fukushima, Y., Inoue, Y., et al.[2023]

In a phase I study with 30 COPD patients, the pharmacokinetic profile of the BGF MDI showed that the maximum plasma concentrations (Cmax) of budesonide and glycopyrronium were similar after both single and chronic dosing, indicating consistent drug absorption.

A phase III sub-study involving 202 patients demonstrated that after 24 weeks of treatment, the pharmacokinetic parameters for budesonide, glycopyrronium, and formoterol in BGF MDI were comparable to other inhalers, suggesting no significant drug interactions and supporting the safety and efficacy of BGF MDI for COPD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler formulated using co-suspension delivery technology after single and chronic dosing in patients with COPD. Dunn, LJ., Kerwin, EM., DeAngelis, K., et al.[2021]

In a Phase III study involving 1896 patients with moderate-to-very-severe COPD, the triple therapy budesonide/glycopyrronium/formoterol (BGF) significantly improved lung function (measured by FEV1) in patients without airway reversibility and low eosinophil counts, compared to other treatments.

BGF also significantly reduced the rate of moderate-to-severe COPD exacerbations compared to glycopyrronium/formoterol (GFF), indicating its efficacy across a broad range of COPD patients, regardless of their eosinophil levels or airway reversibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of budesonide/glycopyrronium/formoterol metered dose inhaler in patients with COPD: post-hoc analysis from the KRONOS study excluding patients with airway reversibility and high eosinophil counts. Muro, S., Sugiura, H., Darken, P., et al.[2021]

In the Phase III KRONOS study involving 1,896 patients with moderate-to-very severe COPD, the budesonide/glycopyrrolate/formoterol fumarate (BGF MDI) inhaler significantly reduced exacerbation rates compared to the glycopyrrolate/formoterol fumarate (GFF MDI) inhaler, regardless of whether patients had a history of exacerbations in the previous year.

The reduction in exacerbation rates with BGF MDI was consistent across patients with and without prior exacerbations, indicating that the benefits of BGF MDI are not solely dependent on a history of exacerbations, and the treatment's efficacy may increase with higher eosinophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Exacerbation Outcomes in Patients with COPD without a Recent Exacerbation History: A Subgroup Analysis of KRONOS. Martinez, FJ., Ferguson, GT., Bourne, E., et al.[2022]

In a Phase I study involving 96 healthy Chinese adults, the pharmacokinetic profiles of the budesonide/glycopyrronium/formoterol fumarate (BGF MDI) and glycopyrronium/formoterol fumarate (GFF MDI) combinations were assessed, showing that budesonide's absorption increased proportionally with dose, indicating effective delivery of the medication.

All treatments were well tolerated with mild adverse events reported, and the pharmacokinetic parameters were comparable to those seen in Western and Japanese populations, suggesting that these combinations are suitable for Chinese patients with COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Tolerability of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate and Glycopyrronium/Formoterol Fumarate Dihydrate Metered Dose Inhalers in Healthy Chinese Adults: A Randomized, Double-blind, Parallel-group Study. Chen, Q., Hu, C., Yu, H., et al.[2022]

In a Phase I study involving 20 healthy Japanese adults, both doses of the BGF MDI (160/14.4/10 μg and 320/14.4/10 μg) were well tolerated, with all reported adverse events being mild to moderate in severity.

The pharmacokinetic analysis showed that the systemic exposure to budesonide increased proportionally with the higher dose, indicating a predictable safety and efficacy profile that is consistent with previous studies in Western populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) in healthy adult subjects of Japanese descent. Dorinsky, P., DePetrillo, P., Siddiqui, S., et al.[2022]

The budesonide/glycopyrronium/formoterol fumarate inhaler (BGF MDI) demonstrated a similar pharmacokinetic profile to the budesonide/formoterol combination, indicating it effectively delivers the medication in a comparable manner, which is crucial for treating COPD.

The study, involving 84 healthy volunteers, showed that BGF MDI had a low rate of adverse events (3.7-17.9%) and no serious adverse events, suggesting it is a safe option for future clinical trials in COPD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of three doses of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler compared with active controls: A Phase I randomized, single-dose, crossover study in healthy adults. Darken, P., DePetrillo, P., Reisner, C., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8384783/

Budesonide/Glycopyrronium/Formoterol: A Review in COPD Discovering the relative efficacy of inhaled medications for chronic obstructive pulmonary disease: multiple treatment comparisons. Cell ...

2. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/Breztri-met-primary-endpoints-in-kalos-and-logos-phase-III-trials-in-asthma.html

BREZTRI met primary endpoints in KALOS and LOGOS ... The trials evaluated the efficacy and safety of BREZTRI versus maintenance treatment with ICS/LABA in adults and adolescents with uncontrolled asthma.

3. astrazeneca.com astrazeneca.com/media-centre/medical-releases/astrazeneca-announces-initiation-tharros-phase-iii-clinical-trial-investigating-potential-breztri-improve-cardiopulmonary-outcomes-people-with-copd.html

a Phase III clinical trial investigating the potential of Breztri ... BGF is approved for patients with COPD under the brand name Trixeo Aerosphere in Europe and Breztri Aerosphere in Japan, China and the US.

4. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2021/SR0675-combined-report.pdf

Formoterol Fumarate Dihydrate (Breztri Aerosphere) BGF = budesonide-glycopyrronium-formoterol fumarate; COPD = chronic obstructive pulmonary disease ... 15 Suissa S Effectiveness of inhaled corticosteroids in ...

5. link.springer.com link.springer.com/article/10.1007/s12325-020-01311-3

Efficacy of Budesonide/Glycopyrronium/Formoterol ... This NMA suggested that BGF MDI has comparable efficacy to other ICS/LAMA/LABA fixed-dose and open triple combination therapies in reducing exacerbations and ...

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

Breztri Aerosphere - accessdata.fda.gov In a 52-week trial of subjects with COPD (n = 8,529), the incidence of confirmed pneumonia was 4.2% for BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg (n = 2144), ...

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00334-7/fulltext

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 ...

8. breztri.com breztri.com/about/safety-information

Safety Information - BREZTRI AEROSPHERE Side Effects People with COPD have a higher chance of getting pneumonia. BREZTRI AEROSPHERE may increase your chance of getting pneumonia. Call your healthcare provider ...