Triple-Inhaler Therapy for COPD

(ATHLOS Trial)

Recruiting in Palo Alto (17 mi)

+29 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Must be taking: Inhaled maintenance

Disqualifiers: Asthma, Lung cancer, Tuberculosis, others

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study will investigate the effect of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) metered dose inhaler (MDI) compared with Placebo MDI, and Budesonide and Formoterol Fumarate (BFF) MDI on isotime inspiratory capacity (IC) and exercise endurance time.

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.

What data supports the effectiveness of the drug combination Budesonide, Formoterol, and Glycopyrronium for COPD?

Research shows that the combination of Budesonide, Formoterol, and Glycopyrronium improves lung function and reduces exacerbation rates in COPD patients compared to dual therapies. This triple therapy is particularly beneficial for patients with severe COPD and those with high eosinophil counts, leading to better quality of life and reduced mortality. ^{1 2 3 4 5}

Is triple-inhaler therapy for COPD safe for humans?

Research shows that triple-inhaler therapy, which includes medications like budesonide, formoterol, and glycopyrronium, is generally safe for people with COPD. Studies have demonstrated its safety and effectiveness in improving symptoms and quality of life over long-term use. ^{1 6 7 8 9}

What makes the triple-inhaler therapy for COPD unique?

The triple-inhaler therapy for COPD, known as Trixeo Aerosphere®, combines three medications—budesonide, formoterol, and glycopyrronium—into a single inhaler, which improves lung function, reduces exacerbation rates, and lowers mortality compared to dual therapies. This combination is particularly beneficial for patients with moderate to severe COPD who are not adequately controlled by other treatments. ^{1 3 5 6 8}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Budesonide (Corticosteroid)
• Formoterol Fumarate (Other)
• Glycopyrronium (Other)
• Placebo (Other)

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.

Participant Groups

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 Canada for the following indications:

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 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]

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]

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]

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 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 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 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]

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]

References

1. England 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Triple inhaled therapy for chronic obstructive pulmonary disease. [2022]

3. Belgium pubmed.ncbi.nlm.nih.gov

[Fixed combination of budesonide, formoterol, glycopyrronium for the treatment of severe COPD : Trixeo Aerosphere®]. [2022]

4. New Zealand 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. [2023]

5. England 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. [2022]

6. England 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. [2022]

7. 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]

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

Patient considerations in the treatment of COPD: focus on the new combination inhaler fluticasone furoate/umeclidinium/vilanterol. [2020]

9. England 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. [2022]