BGF with Different Propellants for COPD

Recruiting in Palo Alto (17 mi)

+85 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Must be taking: LABA, LAMA, ICS

Disqualifiers: Asthma, Tuberculosis, Lung cancer, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to demonstrate that the lung function effect from orally inhaled BGF delivered via HFO propellant is equivalent to the lung function effect from orally inhaled BGF delivered via HFA propellant in participants with COPD. The study duration for each participant will be approximately 15 to 16 weeks and consist of: 1. A screening and placebo run-in period of approximately 2 weeks prior to first dosing 2. Three treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) 3. A final safety follow-up visit via telephone contact approximately 1 to 2 weeks after the final dose administration Participants will be provided with rescue SABA (albuterol or salbutamol) to be used as needed throughout the study. Participants will attend in-clinic study visits approximately weekly during the screening/run-in period (Visits 1, 2, and 3), then every 4 weeks (Visits 4, 5, and 6) to receive take-home study treatment, measure their lung function, and assess their health and safety

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that participants must be willing to adjust their COPD therapy as required by the protocol. You may need to discuss this with the study team to understand what adjustments might be necessary.

What data supports the effectiveness of this drug for COPD?

Research shows that the drug, a combination of budesonide, glycopyrrolate, and formoterol fumarate, reduces exacerbation rates and improves lung function in patients with moderate-to-very severe COPD, as demonstrated in the KRONOS study. ^{1 2 3 4 5}

Is the BGF treatment generally safe for humans?

The BGF treatment has been studied in healthy adults and patients with COPD, showing a low rate of adverse events (3.7-17.9%) without any serious adverse events reported. Long-term safety was also investigated in Japanese patients with COPD, supporting its general safety in humans. ^{1 3 4 6 7}

What makes the BGF MDI drug unique for treating COPD?

The BGF MDI drug is unique because it combines three medications (budesonide, glycopyrronium, and formoterol fumarate) in a single inhaler using co-suspension delivery technology, which helps improve lung function and reduce exacerbations in COPD patients. This triple therapy is designed to provide comprehensive treatment by addressing inflammation, airway constriction, and muscle relaxation in the lungs. ^{1 2 3 4 8}

Research Team

Eligibility Criteria

This trial is for adults aged 40-80 with COPD who have smoked at least the equivalent of 10 pack-years. They must be able to perform proper inhaler and breathing test techniques, have a certain blood cell count and lung function level, and either not be able to bear children or use effective birth control. People can't join if they've had asthma, recent drug/alcohol abuse, certain heart conditions, other respiratory disorders, or are pregnant.

Inclusion Criteria

Your kidney function, as measured by a test called eGFR, needs to be above a certain level.

I am willing to stay at the study center as needed for all visits.

I am between 40 and 80 years old.

Exclusion Criteria

Judgement by the Investigator that the participant should not participate in the study

I have been diagnosed with narrow-angle glaucoma or have problems due to an enlarged prostate.

I will be staying in the hospital during the study.

Trial Timeline

Screening and Placebo Run-in

Participants are screened for eligibility to participate in the trial

2 weeks

3 visits (in-person)

Treatment

Participants undergo three treatment periods of approximately 4 weeks each, receiving BGF MDI HFO, BGF MDI HFA, and Placebo MDI HFA in a randomized sequence

12 weeks

3 visits (in-person) every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

1 visit (telephone contact)

Treatment Details

Interventions

• BGF MDI HFA 320/14.4/9.6 μg (Bronchodilator)
• BGF MDI HFO 320/14.4/9.6μg (Bronchodilator)
• Placebo MDI HFA (Placebo)

Trial Overview The study tests whether BGF medication using a new propellant (HFO) works as well as the approved version with an older propellant (HFA) in improving lung function for COPD patients. Participants will try both versions and a placebo during different periods over about 15-16 weeks while attending regular clinic visits.

Participant Groups

Group I: Treatment Sequence 6 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions in the following sequence. Sequence 6: Placebo MDI HFA BGF MDI HFA 320/14.4/9.6 μg BGF MDI HFO 320/14.4/9.6 μg

Group II: Treatment Sequence 5 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) in the following sequence. Sequence 5: Placebo MDI HFA BGF MDI HFO 320/14.4/9.6 μg BGF MDI HFA 320/14.4/9.6 μg

Group III: Treatment Sequence 4 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) in the following sequence. Sequence 4: BGF MDI HFA 320/14.4/9.6 μg Placebo MDI HFA BGF MDI HFO 320/14.4/9.6 μg

Group IV: Treatment Sequence 3 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) in the following sequence. Sequence 3: BGF MDI HFA 320/14.4/9.6 μg BGF MDI HFO 320/14.4/9.6 μg Placebo MDI HFA

Group V: Treatment Sequence 2 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) in the following sequence. Sequence 2: BGF MDI HFO 320/14.4/9.6 μg Placebo MDI HFA BGF MDI HFA 320/14.4/9.6 μg

Group VI: Treatment Sequence 1 Experimental Treatment 3 Interventions

Each participant will participate in 3 treatment periods of approximately 4 weeks each (one period for each of 3 study interventions) in the following sequence. Sequence 1: BGF MDI HFO 320/14.4/9.6 μg BGF MDI HFA 320/14.4/9.6 μg Placebo MDI HFA

BGF MDI HFA 320/14.4/9.6 μg is already approved in Japan, China for the following indications:

Approved in Japan as Breztri Aerosphere for:

• Chronic Obstructive Pulmonary Disease (COPD)

Approved in China as Breztri Aerosphere for:

• Chronic Obstructive Pulmonary Disease (COPD)

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 28-week extension study involving 416 Japanese patients with moderate-to-very severe COPD, the budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) demonstrated a safety profile comparable to other dual therapies, with similar rates of treatment-emergent adverse events (TEAEs) across all treatment groups.

The most common TEAEs were nasopharyngitis and bronchitis, with a low incidence of major adverse cardiovascular events and pneumonia, indicating that BGF MDI is well tolerated for long-term use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD. Ichinose, M., Fukushima, Y., Inoue, Y., et al.[2023]

In a phase I study with 30 COPD patients, the pharmacokinetic profile of the BGF MDI showed that the maximum plasma concentrations (Cmax) of budesonide and glycopyrronium were similar after both single and chronic dosing, indicating consistent drug absorption.

A phase III sub-study involving 202 patients demonstrated that after 24 weeks of treatment, the pharmacokinetic parameters for budesonide, glycopyrronium, and formoterol in BGF MDI were comparable to other inhalers, suggesting no significant drug interactions and supporting the safety and efficacy of BGF MDI for COPD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler formulated using co-suspension delivery technology after single and chronic dosing in patients with COPD. Dunn, LJ., Kerwin, EM., DeAngelis, K., et al.[2021]

In a Phase III study involving 1896 patients with moderate-to-very-severe COPD, the triple therapy budesonide/glycopyrronium/formoterol (BGF) significantly improved lung function (measured by FEV1) in patients without airway reversibility and low eosinophil counts, compared to other treatments.

BGF also significantly reduced the rate of moderate-to-severe COPD exacerbations compared to glycopyrronium/formoterol (GFF), indicating its efficacy across a broad range of COPD patients, regardless of their eosinophil levels or airway reversibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of budesonide/glycopyrronium/formoterol metered dose inhaler in patients with COPD: post-hoc analysis from the KRONOS study excluding patients with airway reversibility and high eosinophil counts. Muro, S., Sugiura, H., Darken, P., et al.[2021]

In a Phase I study involving 96 healthy Chinese adults, the pharmacokinetic profiles of the budesonide/glycopyrronium/formoterol fumarate (BGF MDI) and glycopyrronium/formoterol fumarate (GFF MDI) combinations were assessed, showing that budesonide's absorption increased proportionally with dose, indicating effective delivery of the medication.

All treatments were well tolerated with mild adverse events reported, and the pharmacokinetic parameters were comparable to those seen in Western and Japanese populations, suggesting that these combinations are suitable for Chinese patients with COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Tolerability of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate and Glycopyrronium/Formoterol Fumarate Dihydrate Metered Dose Inhalers in Healthy Chinese Adults: A Randomized, Double-blind, Parallel-group Study. Chen, Q., Hu, C., Yu, H., et al.[2022]

In the Phase III KRONOS study involving 1,896 patients with moderate-to-very severe COPD, the budesonide/glycopyrrolate/formoterol fumarate (BGF MDI) inhaler significantly reduced exacerbation rates compared to the glycopyrrolate/formoterol fumarate (GFF MDI) inhaler, regardless of whether patients had a history of exacerbations in the previous year.

The reduction in exacerbation rates with BGF MDI was consistent across patients with and without prior exacerbations, indicating that the benefits of BGF MDI are not solely dependent on a history of exacerbations, and the treatment's efficacy may increase with higher eosinophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Exacerbation Outcomes in Patients with COPD without a Recent Exacerbation History: A Subgroup Analysis of KRONOS. Martinez, FJ., Ferguson, GT., Bourne, E., et al.[2022]

The budesonide/glycopyrronium/formoterol fumarate inhaler (BGF MDI) demonstrated a similar pharmacokinetic profile to the budesonide/formoterol combination, indicating it effectively delivers the medication in a comparable manner, which is crucial for treating COPD.

The study, involving 84 healthy volunteers, showed that BGF MDI had a low rate of adverse events (3.7-17.9%) and no serious adverse events, suggesting it is a safe option for future clinical trials in COPD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of three doses of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler compared with active controls: A Phase I randomized, single-dose, crossover study in healthy adults. Darken, P., DePetrillo, P., Reisner, C., et al.[2019]

In a Phase I study involving 20 healthy Japanese adults, both doses of the BGF MDI (160/14.4/10 μg and 320/14.4/10 μg) were well tolerated, with all reported adverse events being mild to moderate in severity.

The pharmacokinetic analysis showed that the systemic exposure to budesonide increased proportionally with the higher dose, indicating a predictable safety and efficacy profile that is consistent with previous studies in Western populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) in healthy adult subjects of Japanese descent. Dorinsky, P., DePetrillo, P., Siddiqui, S., et al.[2022]

References

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

Long-Term Safety and Efficacy of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD. [2023]

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

Pharmacokinetics of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler formulated using co-suspension delivery technology after single and chronic dosing in patients with COPD. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy of budesonide/glycopyrronium/formoterol metered dose inhaler in patients with COPD: post-hoc analysis from the KRONOS study excluding patients with airway reversibility and high eosinophil counts. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Tolerability of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate and Glycopyrronium/Formoterol Fumarate Dihydrate Metered Dose Inhalers in Healthy Chinese Adults: A Randomized, Double-blind, Parallel-group Study. [2022]

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

Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Exacerbation Outcomes in Patients with COPD without a Recent Exacerbation History: A Subgroup Analysis of KRONOS. [2022]

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

The pharmacokinetics of three doses of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler compared with active controls: A Phase I randomized, single-dose, crossover study in healthy adults. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Relative Bioavailability of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Administered With and Without a Spacer: Results of a Phase I, Randomized, Crossover Trial in Healthy Adults. [2020]

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

Safety and pharmacokinetics of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) in healthy adult subjects of Japanese descent. [2022]