BGF Inhaler Comparison for Healthy Adults

Overseen By AstraZeneca Clinical Study Information Center

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: AstraZeneca

Disqualifiers: Respiratory disorders, Cancer, Drug abuse, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study aims to assess the bioequivalence of the total systemic exposure and safety of budesonide, glycopyrronium, and formoterol (160/14.4/4.8 µg/actuation) when administered as BGF MDI HFO compared with BGF MDI HFA in healthy participants.

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.

What data supports the effectiveness of the BGF inhaler drug for healthy adults?

The BGF inhaler, which combines budesonide, glycopyrronium, and formoterol, has been shown to improve lung function and reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD), suggesting its potential effectiveness. Additionally, the study found that the BGF inhaler had higher systemic exposure to its components compared to a similar inhaler, indicating it may deliver the medication more effectively. ^{1 2 3 4 5}

Is the BGF inhaler safe for healthy adults?

The BGF inhaler, which combines budesonide, glycopyrronium, and formoterol, has been tested in healthy adults and was generally well tolerated with no serious side effects reported. Studies showed that the safety profile of BGF is similar to other inhalers containing similar ingredients. ^{1 3 6 7 8}

What makes the BGF inhaler drug unique compared to other treatments?

The BGF inhaler is unique because it combines three components—budesonide, glycopyrronium, and formoterol—using an innovative co-suspension delivery technology, which may enhance the delivery and effectiveness of the medication for conditions like COPD. This combination aims to improve lung function and reduce exacerbations more effectively than dual therapies. ^{1 3 6 9 10}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Budesonide (Corticosteroid)
• Formoterol (Bronchodilator)
• Glycopyrronium (Anticholinergic)

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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 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]

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]

References

1. United States 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. [2020]

2. Australia 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. [2015]

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. India 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. [2018]

5. 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]

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. England 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. [2023]

8. 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]

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

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

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

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