Fixed Dose Triple vs Dual Combination for COPD

(TRITON Trial)

Recruiting at 518 trial locations

Overseen By Chiesi Clinical Trial Info

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Chiesi Farmaceutici S.p.A.

Must be taking: Inhaled maintenance therapy

Must not be taking: Corticosteroids, Antibiotics, Xanthines, Beta-blockers

Disqualifiers: Pregnancy, Respiratory disorders, Cardiovascular conditions, 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: 12

Duration: 52 weeks

3433 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare CHF 5993 with CHF 1535 in improving lung function, reducing moderate and severe COPD exacerbations, and other clinical efficacy and safety outcomes in the target subject population.

Do I need to stop my current medications for this trial?

The trial requires that you stop using certain medications before and during the trial. Specifically, you must not use systemic/oral/parenteral corticosteroids, antibiotics for lower respiratory tract infections or COPD exacerbations, long-term chronic maintenance antibiotics, or oral xanthine derivatives like theophylline within specified periods before the screening visit. Additionally, you cannot be on non-cardioselective β-blockers or require long-term oxygen therapy. If you are on any of these medications, you may need to stop them to participate in the trial.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining, such as oral corticosteroids, antibiotics for respiratory infections, and oral xanthine derivatives. If you're on these, you'll need to stop them for a specific period before the screening.

What data supports the idea that Fixed Dose Triple vs Dual Combination for COPD is an effective drug?

The available research shows that using a Fixed Dose Triple drug, which combines three medications in one inhaler, is more effective for treating COPD than using a Dual Combination drug, which combines only two medications. Studies like the TRILOGY and TRINITY trials found that patients using the triple combination had better outcomes compared to those using the dual combination. This means that people with COPD experienced better breathing and overall health when using the triple combination drug. Additionally, the TRITRIAL study in Italy and the TRICOP study in Austria confirmed these benefits in real-world settings, showing that the triple combination drug is effective and well-tolerated by patients. ^{1 2 3 4 5}

What data supports the effectiveness of the drug for COPD?

Research shows that the combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) in a single inhaler is effective for treating COPD. Studies like TRILOGY and TRINITY have demonstrated its efficacy compared to other treatments, and real-world studies like TRITRIAL and TRICOP have confirmed its effectiveness and tolerability in everyday settings. ^{1 2 3 4 5}

What safety data is available for fixed dose triple vs dual combination therapy for COPD?

The safety of fixed dose triple therapy with beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) has been evaluated in several studies. The TRILOGY and TRINITY trials assessed the efficacy and safety of this combination in COPD patients, showing it to be effective. The TRITRIAL study aims to evaluate its impact in a real-world setting. Additionally, the combination of indacaterol and glycopyrronium bromide (QVA149) has been studied in 14 randomized controlled trials, demonstrating a good safety profile and superior or non-inferior bronchodilator effects compared to other treatments. Overall, these studies suggest that fixed dose triple therapy is safe and effective for COPD treatment. ^{1 2 4 6 7}

Is the fixed-dose triple therapy for COPD safe for humans?

The fixed-dose triple therapy with beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide has been evaluated in several studies and generally shows a good safety profile. It has been compared to other treatments and found to have similar or fewer side effects, making it a safe option for treating COPD. ^{1 2 4 6 7}

Is the drug Beclomethasone Dipropionate, Formoterol Fumarate, Glycopyrronium Bromide a promising treatment for COPD?

Yes, the drug is promising for treating COPD. It combines three medications into one inhaler, which can help improve how well patients stick to their treatment plan and manage their symptoms better. Studies show it can reduce the risk of COPD flare-ups and improve overall health status. ^{1 2 4 5 8}

What makes the drug Beclomethasone/Formoterol/Glycopyrronium unique for COPD treatment?

This drug is unique because it combines three medications into a single inhaler, making it easier for patients to use. It includes an inhaled corticosteroid, a long-acting beta2 agonist, and a long-acting muscarinic antagonist, which together help reduce COPD symptoms and prevent flare-ups more effectively than dual combinations. ^{1 2 4 5 8}

Research Team

Gregory Feldman, MD

Principal Investigator

Vitalink Research - Spartanburg

Eligibility Criteria

This trial is for COPD patients aged 40 or above with a history of smoking and recent exacerbations. They must have used stable inhaled maintenance therapy for at least 3 months, demonstrate correct inhaler use, and agree to birth control if applicable. Cancer patients, those under age 50 without COPD diagnosis, or hospital visits for COPD within the last year are excluded.

Inclusion Criteria

You have a pre- and post-bronchodilator FEV1/FVC ratio <0.

I have been diagnosed with COPD for over a year.

Documentation (including imagery and report) of chest x-ray (CXR) or CT scan performed within 6 months prior to the screening visit, without evidence of significant abnormalities (other than those related to the presence of COPD).

Exclusion Criteria

I've been to the hospital or doctor for my COPD getting worse in the last year.

Do you have any uncontrolled heart conditions? (Afib, heart disease, acute myocardial infraction) in the last 6 months?

Do you use a nebulizer to take your medication?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Run-in

Participants continue their regular COPD maintenance therapies before randomization

2 weeks

1 visit (in-person)

Treatment

Participants receive either CHF 5993 or CHF 1535 for 52 weeks with assessments at 4 weeks and every 6 weeks thereafter

52 weeks

9 visits (in-person)

Follow-up

A follow-up safety phone call is performed a week after the last clinic visit

1 week

1 call (virtual)

Treatment Details

Interventions

• Beclomethasone Dipropionate
• Formoterol Fumarate
• Glycopyrronium Bromide

Trial Overview The study compares two treatments: CHF 5993 (a triple combination) versus CHF 1535 (a dual combination), both containing drugs that help improve lung function. It aims to see which one better reduces lung issues and is safer over time.

Participant Groups

Group I: BDP/FF/GB - CHF 5993 Experimental Treatment 3 Interventions

Two inhalations twice daily of BDP/FF/GB (100/6/12.5μg) for a period of 52 weeks via pressurized metered dose inhaler

Group II: BDP/FF - CHF 1535 Active Control 2 Interventions

Two inhalations twice daily of BDP/FF (100/6μg) for a period of 52 weeks via pressurized metered dose inhaler

Beclomethasone Dipropionate is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Beclomethasone Dipropionate for:

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)
• Allergic Rhinitis
• Dermatoses

Approved in United States as Beclomethasone Dipropionate for:

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)
• Allergic Rhinitis

Approved in Canada as Beclomethasone Dipropionate for:

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)
• Allergic Rhinitis

Approved in Japan as Beclomethasone Dipropionate for:

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)
• Allergic Rhinitis

Who Is Running the Clinical Trial?

Chiesi Farmaceutici S.p.A.

Lead Sponsor

Trials

206

Recruited

315,000+

Founded

1935

Headquarters

Parma, Italy

Known For

Respiratory diseases

Top Products

NEXThaler, Trimbow, Curosurf, Holoclar

Findings from Research

The TRITRIAL study is a 12-month observational study involving 800 COPD patients in Italy, aimed at assessing the real-world effectiveness of the fixed triple combination therapy BDP/FF/G, focusing on changes in health status as measured by the CAT score.

This study will also evaluate important factors such as patient adherence, quality of life, and device usability, which are critical for the successful management of COPD in everyday clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Fixed Triple Therapy with Beclometasone/Formoterol/Glycopyrronium on Health Status and Adherence in Chronic Obstructive Pulmonary Disease (COPD) in an Italian Context of Real Life: The TRITRIAL Study Protocol. Richeldi, L., Piraino, A., Macagno, F., et al.[2022]

In a study involving 2691 patients with severe COPD, the fixed triple therapy (beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide) significantly reduced the rate of moderate-to-severe exacerbations compared to tiotropium alone, demonstrating its superior efficacy.

The fixed triple therapy also showed a significant improvement in lung function (measured by FEV1) compared to tiotropium, while being non-inferior to the open triple therapy, indicating its effectiveness in managing COPD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial. Vestbo, J., Papi, A., Corradi, M., 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]

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 involving 708 patients with COPD, the extrafine combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) significantly improved lung function compared to the non-extrafine budesonide/formoterol (BUD/FF) after 24 weeks, with greater increases in both pre-dose and post-dose FEV1.

BDP/FF/G also reduced the rate of moderate to severe COPD exacerbations by 43% compared to BUD/FF, indicating its superior efficacy in managing COPD symptoms and preventing flare-ups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of single-inhaler extrafine triple therapy versus inhaled corticosteroid plus long-acting beta2 agonist in eastern Asian patients with COPD: the TRIVERSYTI randomised controlled trial. Zheng, J., Baldi, S., Zhao, L., et al.[2021]

The fixed-dose combination of indacaterol, glycopyrronium, and mometasone furoate (IND/GLY/MF) was found to be non-inferior to the combination of salmeterol/fluticasone and tiotropium (SAL/FLU + TIO) in improving asthma quality of life after 24 weeks in patients with uncontrolled asthma, based on a study involving adults aged 18 and older.

IND/GLY/MF high-dose not only matched the efficacy of SAL/FLU + TIO but also showed significant improvements in lung function and asthma control, while the medium-dose provided similar benefits with a lower steroid dose, indicating a potentially safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON). Gessner, C., Kornmann, O., Maspero, J., et al.[2021]

QVA149, a once-daily dual-bronchodilator therapy combining indacaterol and glycopyrronium bromide, has been shown to have a good safety profile and effective bronchodilation in 14 randomized controlled trials, making it a promising treatment for chronic obstructive pulmonary disease (COPD).

Meta-analysis results indicate that QVA149 is superior to the salmeterol-fluticasone combination in reducing adverse effects and exacerbations, while also improving lung function as measured by forced expiratory volume in 1 second (FEV1).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of combined indacaterol and glycopyrronium bromide (QVA149) for the treatment of COPD in Japan. Horita, N., Kaneko, T.[2020]

Triple fixed-dose combination therapies (FDCs) for COPD, such as BDP/FOR/GLY, FF/UMEC/VI, and BUD/GLY/FOR, have been shown to significantly reduce the risk of exacerbations compared to standard ICS/LABA and LABA/LAMA treatments.

While these therapies improve adherence and management of COPD, there are concerns about an increased risk of pneumonia with certain FDCs, and the results from pivotal randomized-controlled trials should be interpreted cautiously due to potential confounding factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of triple combination therapy for treating chronic obstructive pulmonary disease: an expert review. Ritondo, BL., Puxeddu, E., Calzetta, L., et al.[2021]

References

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

The Impact of Fixed Triple Therapy with Beclometasone/Formoterol/Glycopyrronium on Health Status and Adherence in Chronic Obstructive Pulmonary Disease (COPD) in an Italian Context of Real Life: The TRITRIAL Study Protocol. [2022]

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

Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial. [2022]

3. 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]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of single-inhaler extrafine triple therapy versus inhaled corticosteroid plus long-acting beta2 agonist in eastern Asian patients with COPD: the TRIVERSYTI randomised controlled trial. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON). [2021]

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

Role of combined indacaterol and glycopyrronium bromide (QVA149) for the treatment of COPD in Japan. [2020]

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

Efficacy and safety of triple combination therapy for treating chronic obstructive pulmonary disease: an expert review. [2021]