Combination Inhalers for COPD

(THARROS Trial)

Recruiting at 420 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: LAMA, LABA

Must not be taking: Maintenance ICS

Disqualifiers: Asthma, Lung cancer, Renal disease, 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: Up to 3 years

5000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of inhalers to evaluate their effectiveness in improving heart and lung health in people with COPD, a chronic lung disease that makes breathing difficult. It compares a triple therapy inhaler (Budesonide, Glycopyrronium, and Formoterol Fumarate) to a dual therapy inhaler. The trial seeks current or former smokers with COPD who also have heart health concerns, such as high blood pressure or diabetes. Participants must be comfortable using an inhaler and willing to adjust their current COPD medications as part of the study. 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.

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 current COPD therapy as required by the protocol. It's best to discuss your specific medications with the study team.

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

Research has shown that the treatment combining Budesonide, Glycopyrronium, and Formoterol, often used for COPD, was well-tolerated in past studies. In one study, patients using this combination experienced fewer deaths from all causes. Another study confirmed its safety, noting common side effects like mild throat infections and colds.

Studies also support the safety of the Glycopyrronium and Formoterol combination. Common side effects included throat infections and colds, similar to the triple combination. Overall, both treatments have demonstrated safety for people with COPD. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination inhalers for COPD because they integrate multiple active ingredients—Budesonide, Glycopyrronium, and Formoterol Fumarate—into one treatment. Unlike standard treatments, which often require separate inhalers for different medications, these combination inhalers simplify the regimen by delivering all three components together. Budesonide helps reduce inflammation, Glycopyrronium acts as a bronchodilator to open airways, and Formoterol Fumarate provides long-lasting relief. This all-in-one approach not only enhances convenience but may also improve medication adherence and overall lung function for patients with COPD.

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

Research has shown that a single inhaler containing three medications—budesonide, glycopyrronium, and formoterol—can effectively treat people with COPD. In this trial, participants in the BGF arm will receive this combination, which has improved lung function and reduced symptoms more than using just two of these medications together. One study found that BGF significantly improved breathing tests compared to using only glycopyrronium and formoterol. Participants in the GFF arm will receive glycopyrronium and formoterol alone, which has also maintained long-term improvements in lung function for people with COPD. Both treatment options in this trial have shown promise in managing COPD symptoms and improving quality of life. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with Chronic Obstructive Pulmonary Disease (COPD) who are at high risk of heart and lung complications. Participants should not have other health conditions that could interfere with the study or be using certain medications.

Inclusion Criteria

Are you a current or former smoker?

Exclusion Criteria

Do you have a history of heart or lung transplant or lung cancer?

Have you experienced pneumonia or COPD exacerbation within the past 8 weeks that has not yet been resolved?

Are you participating in another study?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either BGF MDI 320/14.4/9.6 μg BID or GFF MDI 14.4/9.6 μg BID to evaluate cardiopulmonary outcomes

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including severe COPD exacerbations and cardiac events

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Budesonide
• Glycopyrronium and Formoterol Fumarate

Trial Overview The study tests a combination inhaler therapy (BGF MDI) against a dual therapy inhaler (GFF MDI). It aims to see if adding an extra drug to the usual treatment can improve heart and lung function in COPD patients.

How Is the Trial Designed?

Group I: GFF arm Experimental Treatment 1 Intervention

GFF MDI 14.4/9.6 μg BID

Group II: BGF arm Experimental Treatment 1 Intervention

BGF MDI 320/14.4/9.6 μg BID

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]

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 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 PINNACLE trials, glycopyrronium/formoterol significantly improved lung function in patients with moderate to very severe COPD compared to its individual components and placebo over 24 weeks, demonstrating its efficacy as a maintenance treatment.

Glycopyrronium/formoterol was generally well tolerated, with most adverse events being mild or moderate, indicating a favorable safety profile for patients with COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycopyrronium/Formoterol: A Review in COPD. Al-Salama, ZT., Frampton, JE.[2020]

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]

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 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]

The fixed combination of budesonide and formoterol fumarate dihydrate is an effective treatment option for asthma in adolescents and adults, providing both maintenance and reliever therapy in a single inhaler, which enhances convenience for patients.

This combination therapy has been shown to reduce the frequency of asthma exacerbations that require oral corticosteroids, although more research is needed to confirm its impact on serious outcomes like hospital admissions and emergency visits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide + formoterol fumarate dihydrate for the treatment of asthma. Wolthers, OD.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11994078/

Characteristics of Patients Receiving Budesonide ... Single-inhaler budesonide/glycopyrronium/formoterol fumarate (BGF; Trixeo Aerosphere®) was efficacious when compared with the corresponding dual ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06321731?term=BUDESONIDE%20AND%20FORMOTEROL%20AND%20GLYCOPYRRONIUM&rank=7

Real-World Outcomes in COPD Patients Starting Trixeo ... The aim of the ORESTES study is to describe the characteristics of the COPD patients initiating Trixeo (BGF - budesonide / glycopyrronium / formoterol ) in ...

3. link.springer.com link.springer.com/article/10.1007/s12325-025-03361-x

Real-World Outcomes in Patients with COPD Initiating ... Characteristics of patients receiving budesonide/glycopyrronium/formoterol for chronic obstructive pulmonary disease in Spain: The AURA Study.

4. 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.

5. bmj.com bmj.com/content/387/bmj-2024-080409

Comparative effectiveness and safety of single inhaler ... Budesonide-glycopyrrolate-formoterol was not associated with improved clinical outcomes compared with fluticasone-umeclidinium-vilanterol.

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

Budesonide/Glycopyrronium/Formoterol: A Review in COPD Reduced all-cause mortality in the ETHOS trial of budesonide/glycopyrrolate/formoterol for chronic obstructive pulmonary disease. A ...

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. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/breztri-met-primary-endpoints-in-ph3-asthma-trials.html

Breztri met primary endpoints in KALOS and LOGOS ... The results from the KALOS and LOGOS trials are exciting and demonstrate the potential of budesonide/glycopyrronium/formoterol to evolve the ...