Combination Inhalers for COPD

(THARROS Trial)

Recruiting at 421 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

Trial Summary

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.

What data supports the effectiveness of the drug combination inhalers for COPD?

Research shows that the combination of budesonide, glycopyrronium, and formoterol in inhalers like Breztri Aerosphere and Trixeo Aerosphere helps reduce COPD flare-ups, improves lung function, and enhances quality of life. These inhalers are more effective than using just two of the components together and can also lower the risk of death in patients with COPD. ^{1 2 3 4 5}

Is the combination inhaler for COPD safe for humans?

The combination inhaler containing budesonide, glycopyrronium, and formoterol is generally well tolerated in humans, with most side effects being mild or moderate. It has been tested in clinical trials for COPD and shown to have a safety profile similar to its individual components. ^{2 3 4 5 6}

How is the drug Budesonide/Glycopyrronium/Formoterol unique for treating COPD?

This drug is unique because it combines three medications in one inhaler to help manage COPD: budesonide (a steroid to reduce inflammation), glycopyrronium (a long-acting muscarinic antagonist to open airways), and formoterol (a long-acting beta-agonist to relax muscles in the airways). It has been shown to improve lung function and reduce COPD flare-ups more effectively than some dual therapies. ^{1 2 3 7 8}

What is the purpose of this trial?

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 GFF MDI 14.4/9.6 μg in a population with COPD and elevated cardiopulmonary risk.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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]

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]

References

1. 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]

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

Budesonide/Glycopyrronium/Formoterol: A Review in COPD. [2022]

3. 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]

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

Glycopyrronium/Formoterol: A Review in COPD. [2020]

5. Belgium pubmed.ncbi.nlm.nih.gov

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

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Symbicort: a pharmacoeconomic review. [2018]