Triple-Inhaler Therapy for COPD

(ATHLOS Trial)

Recruiting at 34 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Inhaled maintenance

Disqualifiers: Asthma, Lung cancer, Tuberculosis, others

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: 6 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new inhaler combination treatment for people with Chronic Obstructive Pulmonary Disease (COPD). Researchers aim to determine if adding Glycopyrronium (a bronchodilator) to the usual mix of Budesonide (a corticosteroid) and Formoterol Fumarate (a long-acting bronchodilator) improves lung function and exercise endurance. Participants will use either the new inhaler combo, the standard inhaler, or a placebo (a treatment without active medicine). This trial suits individuals diagnosed with moderate to severe COPD who have been on stable treatment and often struggle to breathe during physical activity. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for COPD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of your current COPD inhaler treatment for at least 6 weeks before joining.

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

Research has shown that the treatments under study—BGF MDI and BFF MDI—are generally safe for people. In earlier studies, participants tolerated these treatments well for up to a year. The safety profile of BGF MDI matched that of other common COPD treatments, indicating no increase in expected side effects.

For BFF MDI, studies found no unexpected safety issues. Patients using this treatment experienced improved lung function, and it was well-tolerated without serious side effects. This suggests that both treatments might be safe options for managing COPD symptoms, based on the available data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for COPD because they combine multiple active ingredients in a single inhaler. The BGF MDI combines Budesonide, Glycopyrronium, and Formoterol Fumarate, offering both anti-inflammatory and bronchodilation effects in one device, which is more convenient than using separate inhalers for each medication. The BFF MDI provides a combination of Budesonide and Formoterol Fumarate, focusing on reducing inflammation and improving airflow. These combinations could simplify treatment regimens and improve adherence, potentially leading to better overall outcomes for patients with COPD.

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

Research shows that the BGF MDI, a treatment in this trial, combines Budesonide, Glycopyrronium, and Formoterol Fumarate, significantly aiding people with COPD by improving symptoms and quality of life. Studies have found that this triple therapy boosts lung function and increases exercise endurance, making daily activities easier. The BGF MDI improves scores on tests measuring breathing problems and overall health, such as the COPD Assessment Test (CAT) and the St. George's Respiratory Questionnaire (SGRQ). Meanwhile, the BFF MDI, another treatment option in this trial, contains Budesonide and Formoterol Fumarate, and it also enhances lung function and reduces the risk of flare-ups. Both treatments effectively manage COPD symptoms. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 40-80 with moderate to severe COPD who are current or former smokers. They must have a BMI < 40 kg/m2, stable on COPD treatment for at least 6 weeks, and not be using oxygen therapy or have certain health conditions like untreated glaucoma, significant cancers, or recent drug abuse.

Inclusion Criteria

I can exercise at a steady pace for 3 to 8 minutes.

I am between 40 and 80 years old.

I have smoked at least 10 pack-years.

Exclusion Criteria

I am enrolled in or will join a lung rehab program during the study.

I have untreated narrow-angle glaucoma or vision changes that may be important.

I was hospitalized or used oral steroids for COPD flare-up in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BGF MDI, BFF MDI, or Placebo MDI in a three-period, three-treatment, cross-over design

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Extension

Optional continuation of treatment for further observation

What Are the Treatments Tested in This Trial?

Interventions

• Budesonide
• Formoterol Fumarate
• Glycopyrronium
• Placebo

Trial Overview The study tests the effects of two inhalers: one with Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF), another with just Budesonide and Formoterol Fumarate (BFF), against a placebo. It measures how these treatments impact breathing capacity and exercise endurance in COPD patients.

How Is the Trial Designed?

Group I: BGF MDI Active Control 1 Intervention

Pressurized MDI fixed combination product of Budesonide 160 μg, Glycopyrronium 7.2 μg, and Formoterol Fumarate 4.8 μg per actuation.

Group II: BFF MDI Active Control 1 Intervention

Pressurized MDI fixed combination product of Budesonide 160 μg and Formoterol Fumarate 4.8 μg per actuation.

Group III: Placebo Placebo Group 1 Intervention

Placebo as pressurized inhalation suspension.

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

In a study involving 1368 patients with COPD, the triple therapy combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) significantly improved lung function compared to the dual therapy of beclometasone dipropionate and formoterol fumarate (BDP/FF), with notable increases in pre-dose and 2-hour post-dose FEV1 measurements.

Patients using BDP/FF/GB experienced a 23% reduction in moderate-to-severe COPD exacerbations compared to those on BDP/FF, indicating enhanced efficacy in managing COPD symptoms and preventing flare-ups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Singh, D., Papi, A., Corradi, M., et al.[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]

A new inhaler combination of fluticasone furoate, umeclidinium, and vilanterol has been shown to effectively reduce exacerbation rates in patients with stable COPD, based on a large clinical trial.

This combination therapy is safe and convenient, requiring only a single daily administration through a dry powder inhaler, which improves patient adherence and preference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient considerations in the treatment of COPD: focus on the new combination inhaler fluticasone furoate/umeclidinium/vilanterol. Molino, A., Calabrese, G., Maniscalco, M.[2020]

In a study of 2409 COPD patients, those who received the triple therapy budesonide/glycopyrrolate/formoterol fumarate (BGF) promptly after an exacerbation experienced significantly fewer subsequent exacerbations compared to those who started treatment later.

Prompt initiation of BGF not only reduced the rate of exacerbations but also led to lower healthcare costs, with annualized costs of $5002 for prompt treatment versus $7639 and $8724 for delayed and very delayed treatments, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exacerbations and Real-World Outcomes After Single-Inhaler Triple Therapy of Budesonide/Glycopyrrolate/Formoterol Fumarate, Among Patients with COPD: Results from the EROS (US) Study. Strange, C., Tkacz, J., Schinkel, J., et al.[2023]

In a phase 3 study involving 396 COPD patients, the single-inhaler triple therapy (GB/FF/FP) demonstrated comparable efficacy in improving lung function (measured by FEV1) to the open-triple therapy (GB+FF/FP) over 12 weeks, indicating it is an effective treatment option.

Both treatment groups reported similar rates of mild to moderate adverse events (around 25%), suggesting that the single-inhaler therapy is safe and well tolerated for patients with COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of single-inhaler triple therapy of glycopyrronium, formoterol and fluticasone in patients with COPD: a double-blind, randomised controlled trial. Salvi, S., Balki, A., Krishnamurthy, S., et al.[2022]

In the Phase III ETHOS study involving 8509 patients with moderate-to-very severe COPD, triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) significantly reduced the use of rescue medication compared to dual therapies, indicating better control of symptoms over 52 weeks.

BGF therapy also led to significant improvements in health-related quality of life, as measured by the St George's Respiratory Questionnaire, with a higher proportion of patients reporting improvements compared to those on dual therapies at both 24 and 52 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of budesonide/glycopyrrolate/formoterol fumarate (BGF) on symptoms and quality of life in patients with COPD in the ETHOS trial. Martinez, FJ., Rabe, KF., Ferguson, GT., et al.[2022]

Combining a long-acting muscarinic antagonist (LAMA) with an inhaled corticosteroid (ICS) and long-acting β2-adrenoceptor agonist (LABA) in a single inhaler can enhance the treatment effectiveness for patients with chronic obstructive pulmonary disease (COPD).

New fixed-dose combinations of ICS/LABA/LAMA, such as fluticasone furoate/vilanterol/umeclidinium, are currently in Phase III clinical trials and may be particularly beneficial for patients with severe COPD, especially those with specific characteristics like high eosinophil counts or frequent exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple inhaled therapy for chronic obstructive pulmonary disease. Montuschi, P., Malerba, M., Macis, G., et al.[2022]

In a real-world study of 265 COPD patients over 52 weeks, the single-inhaler triple therapy (beclometasone-dipropionate, formoterol-fumarate, and glycopyrronium) significantly improved lung function and reduced symptoms, with a notable 57.4% reduction in moderate and severe exacerbations.

The treatment was well-tolerated, with 93.7% of patients continuing after a year, and while there were 21 reported adverse events, none were deemed drug-related, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TRICOP - A Real-world effectiveness study with a single-inhaler extrafine triple therapy over 52 weeks in Austrian patients with COPD. Marth, K., Renner, A., Pohl, W.[2021]

Trixeo Aerosphere®, a new inhaled combination treatment for severe COPD, significantly improves lung function (FEV1) compared to a budesonide/formoterol combination.

This triple therapy not only reduces the rate of exacerbations and improves quality of life but also lowers mortality rates, especially in patients with higher blood eosinophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fixed combination of budesonide, formoterol, glycopyrronium for the treatment of severe COPD : Trixeo Aerosphere®]. Louis, R., Bonhomme, O., Heinen, V., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35815354/

Effect of inhaled budesonide/formoterol fumarate dihydrate ... Conclusion: Dual therapy with BFF MDI and with BUD/FORM DPI led to improvements in lung function in patients with severe-to-very severe COPD and low PIF.

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

Safety and efficacy of budesonide/glycopyrrolate/formoterol ... BGF MDI may offer better long-term management for moderate to severe COPD. Background. Chronic obstructive pulmonary disease (COPD) is a ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7184113/

Efficacy and safety of two doses of budesonide/formoterol ... Co-suspension delivery technology budesonide/formoterol fumarate metered dose inhaler improve lung function and reduce exacerbation risk versus LABA ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06283966

NCT06283966 | A Study Evaluating the Efficacy of ... This study will evaluate the effect of triple ICS/LAMA/LABA therapy with BGF MDI 320/14.4/9.6 μg on cardiopulmonary outcomes relative to LAMA/LABA therapy with ...

5. 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.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6383599/

Budesonide/formoterol MDI with co-suspension delivery ... The TELOS study examined the efficacy and safety of 24 weeks of treatment with two doses of BFF MDI (320/10 µg and 160/10 µg) compared with BD ...

7. link.springer.com link.springer.com/article/10.1007/s40801-025-00522-w

Outcomes and Usability of Formoterol-Budesonide ... The treatment using Synchrobreathe® inhaler was well tolerated, with no serious adverse events reported, supporting its practical use in routine ...

8. atsjournals.org atsjournals.org/doi/pdf/10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A6298?download=true

Cardiovascular Safety of Budesonide/Glycopyrrolate/ ... Cardiovascular Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose ... combination therapy for chronic obstructive pulmonary disease (COPD). The ...