BGF Inhaler Comparison for Healthy Adults

Overseen By AstraZeneca Clinical Study Information Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Disqualifiers: Respiratory disorders, Cancer, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 3 periods with 5-7 days washout between doses

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two versions of an inhaler containing budesonide, glycopyrronium, and formoterol, medications that help improve breathing. Researchers aim to determine if the new inhaler version (BGF MDI HFO) is as safe and effective as the current one (BGF MDI HFA). The trial seeks healthy adults with no history of breathing problems, such as asthma or COPD, who can use an inhaler correctly. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new inhaler.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study is for healthy participants without significant medical conditions, it's likely that you should not be on any regular medications. Please consult with the trial coordinators for specific guidance.

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

Research shows that the BGF inhaler, which combines budesonide, glycopyrronium, and formoterol, is generally well-tolerated. In studies with patients who have chronic obstructive pulmonary disease (COPD), most participants did not experience serious side effects from using the BGF inhaler.

One study found that only about 4.2% of participants developed pneumonia after using the BGF MDI HFA inhaler for a year. The BGF MDI HFO inhaler, which uses a new type of propellant, demonstrated similar safety results. Over 12 weeks, participants reported no serious side effects.

These findings suggest that these treatments are safe. However, it's important to note that this study focused on healthy adults. Prospective participants should discuss their health conditions with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the BGF inhaler treatments because they offer a new approach to managing respiratory conditions with a combination of budesonide, formoterol, and glycopyrronium. While traditional inhalers often focus on one or two active ingredients, the BGF inhalers combine three, potentially providing enhanced symptom control and improved lung function. Additionally, the BGF MDI HFO uses a novel delivery system, which might offer more effective drug delivery compared to current options. This innovative combination and delivery method could lead to quicker relief and better outcomes for patients.

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

Research has shown that the BGF inhaler, which combines budesonide, glycopyrronium, and formoterol, effectively treats COPD, a lung condition that makes breathing difficult. Studies indicate that this combination therapy significantly improves lung function and reduces moderate to severe flare-ups. The BGF inhaler also enhances quality of life, as measured by specific tests, over 12 weeks. In this trial, participants will receive either the BGF MDI HFA or the BGF MDI HFO formulation. Clinical data confirm that both versions of the BGF inhaler are safe and effective, providing similar benefits. Both types are well-tolerated, making them a good treatment option for breathing problems. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

Healthy adults who can use an MDI device correctly, have a BMI of 18-30 kg/m2, weigh between 50-120 kg, and have normal lung function (FEV1 ≥80% predicted). Women must not be pregnant or breastfeeding and if able to bear children, must use effective contraception.

Inclusion Criteria

My lung function tests are within the normal range.

My BMI is between 18 and 30, and I weigh between 50 kg and 120 kg.

I am a woman who cannot become pregnant, confirmed at my screening visit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 27 days

Treatment

Participants receive single doses of BGF MDI HFO and BGF MDI HFA in a 3-way cross-over design with washout periods

3 periods with 5-7 days washout between doses

Follow-up

Participants are monitored for safety within 5 to 7 days after the last administration of the study intervention

5 to 7 days

What Are the Treatments Tested in This Trial?

Interventions

• Budesonide
• Formoterol
• Glycopyrronium

Trial Overview The trial is testing the bioequivalence of BGF delivered by two different inhalers: one using HFO propellant and the other HFA. It's checking if both deliver similar amounts of medication into the body safely in healthy people.

How Is the Trial Designed?

Group I: BGF MDI HFO Experimental Treatment 1 Intervention

Participants will receive single doses (2 inhalations as a single dose) of test formulation BGF MDI HFO

Group II: BGF MDI HFA Active Control 1 Intervention

Participants will receive single doses (2 inhalations as a single dose) of reference formulation BGF MDI HFA

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

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

A study of 30,339 COPD patients initiating budesonide/glycopyrrolate/formoterol fumarate (BGF) revealed that a significant 57.9% had experienced exacerbations or related events in the year prior, indicating a need for effective management despite existing treatments.

The patient population was characterized by a high prevalence of comorbidities, particularly cardiopulmonary conditions, with 54.3% having received oral corticosteroids, suggesting that BGF is being prescribed to patients with complex health profiles and ongoing respiratory challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of initiators of budesonide/glycopyrrolate/formoterol for treatment of chronic obstructive pulmonary disease (COPD) in the United States: the AURA study. Portillo, EC., Pollack, M., Lee, I., et al.[2023]

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]

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 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]

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 1 study involving 72 healthy adults, the budesonide/glycopyrronium/formoterol fumarate metered dose inhaler (BGF MDI) demonstrated similar pharmacokinetic profiles to the budesonide/formoterol fumarate metered dose inhaler (BFF MDI), indicating bioequivalence for the active ingredients.

All inhaler treatments were well tolerated, and despite higher systemic exposure to budesonide and formoterol with BGF MDI and BFF MDI compared to the dry powder inhaler (BUD/FORM DPI), there were no significant differences in adverse events, suggesting a comparable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Co-Suspension Delivery Technology Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate (BGF MDI) and Budesonide/Formoterol Fumarate Dihydrate (BFF MDI) Fixed-Dose Combinations Compared With an Active Control: A Phase 1, Randomized, Single-Dose, Crossover Study in Healthy Adults. Maes, A., DePetrillo, P., Siddiqui, S., et al.[2020]

In a study involving 1,293 patients with moderate to severe COPD, budesonide/formoterol significantly improved lung function (FEV1) more than formoterol alone, with an increase of 4.6% compared to 1.5%.

Budesonide/formoterol also resulted in a longer time to first exacerbation compared to formoterol, indicating better overall management of COPD symptoms, while both treatments were well tolerated with similar adverse event profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide/formoterol via Turbuhaler® versus formoterol via Turbuhaler® in patients with moderate to severe chronic obstructive pulmonary disease: phase III multinational study results. Fukuchi, Y., Samoro, R., Fassakhov, R., et al.[2015]

Patients with asthma treated with budesonide/formoterol had a 44% higher probability of treatment success compared to those on salmeterol/fluticasone, indicating better overall management of their condition.

Budesonide/formoterol also resulted in significantly lower healthcare costs, with a 12.6% reduction in total costs and fewer severe exacerbations and oral corticosteroid prescriptions, suggesting it is a more effective and economical treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective database study comparing treatment outcomes and cost associated with choice of fixed-dose inhaled corticosteroid/long-acting beta-agonists for asthma maintenance treatment in Germany. Aballéa, S., Cure, S., Vogelmeier, C., et al.[2018]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40513294/

EBISU study Triple therapy with a BGF MDI significantly improved CAT and SGRQ scores over 12 weeks. BGF MDI could be a suitable option for patients living with COPD.

2. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00334-7/fulltext

Safety of budesonide/glycopyrronium/formoterol fumarate ... Budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) is a triple therapy pMDI approved as a maintenance therapy for patients with COPD ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05573464

NCT05573464 | A Study to Assess the Safety of ... This is a Phase 3 randomized, double-blind, 12-week (with an extension to 52 weeks in a subset of participants) study comparing the safety of BGF MDI HFO ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1094553923000573

Relative bioavailability of budesonide/glycopyrrolate/ ... This study evaluated the relative bioavailabilities of the individual components of a fixed-dose combination of budesonide/glycopyrrolate/formoterol fumarate ( ...

5. canjhealthtechnol.ca canjhealthtechnol.ca/index.php/cjht/article/view/sr0675r/357

View of Budesonide-Glycopyrronium-Formoterol Fumarate ... Overall, BGF MDI 320 reduced the rate of moderate or severe exacerbations compared with GFF MDI and BFF MDI at 52 weeks. Although numerical improvements in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12359160/

Safety of budesonide/glycopyrronium/formoterol fumarate ... Budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) is a triple therapy pMDI approved as a maintenance therapy for patients with COPD ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/212122s000lbl.pdf

Breztri Aerosphere - accessdata.fda.gov In a 52-week trial of subjects with COPD (n = 8,529), the incidence of confirmed pneumonia was 4.2% for BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg (n = 2144), ...

8. astrazeneca.ca astrazeneca.ca/content/dam/az-ca/downloads/productinformation/breztri-aerosphere-product-monograph-en.pdf

breztri-aerosphere-product-monograph-en. ... Inhalation use. Pressurized inhalation suspension. 160 mcg budesonide / 7.2 mcg glycopyrronium (as bromide) / 5 mcg formoterol fumarate.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40831469/

Safety of budesonide/glycopyrronium/formoterol fumarate ... Safety of budesonide/glycopyrronium/formoterol fumarate dihydrate delivered by HFO-1234ze versus HFA-134a in chronic obstructive pulmonary ...