Budesonide/Albuterol vs Albuterol for Asthma

(ACADIA Trial)

Recruiting at 110 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Inhaled corticosteroids

Must not be taking: Oral corticosteroids

Disqualifiers: Life-threatening asthma, Significant lung disease, Cancer, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

440 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new combination inhaler, budesonide/albuterol (a metered-dose inhaler), is more effective than the standard albuterol inhaler in controlling severe asthma attacks. Individuals with asthma for at least a year and who have experienced at least one severe attack in the past year might be suitable candidates. The study compares the frequency of severe asthma flare-ups when using either the budesonide/albuterol inhaler or the regular albuterol inhaler as needed. Participants must maintain stable asthma treatment and use the inhalers correctly. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in asthma treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you have been on a stable dose of certain asthma maintenance therapies for at least one month before joining. You will also need to use the albuterol sulfate inhaler provided by the study.

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

Research shows that the budesonide/albuterol inhaler (BDA MDI) is generally easy for most people to use. Studies found that people using this inhaler experienced fewer severe asthma attacks, resulting in fewer hospital visits and less emergency care.

Some individuals reported mild side effects, such as throat irritation or headaches, while using BDA MDI. However, these side effects were uncommon and usually not serious. The FDA has approved the ingredients in this inhaler for other treatments, indicating their safety.

For those considering joining a trial, it is reassuring to know that this treatment has undergone extensive testing. The goal is to ensure its safety while improving asthma management. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Budesonide/Albuterol metered-dose inhaler (BDA MDI) because it combines two active ingredients—budesonide, a steroid that reduces inflammation, and albuterol, a bronchodilator for quick relief. Unlike the standard asthma treatments that often involve separate inhalers for a steroid and a bronchodilator, BDA MDI offers the convenience of both in one device. This combination could potentially provide both immediate relief and long-term control, making asthma management simpler and more effective. Plus, the dual-action approach targets both inflammation and airway constriction simultaneously, which could lead to improved outcomes for asthma patients.

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

This trial will compare the effectiveness of the budesonide/albuterol inhaler with the albuterol inhaler for treating asthma. Research has shown that the budesonide/albuterol inhaler can significantly lower the risk of severe asthma flare-ups by 27% compared to albuterol alone. One study found that individuals using the budesonide/albuterol combination experienced fewer severe asthma episodes annually, with a rate of 0.43 for the combination treatment compared to 0.58 for higher doses of other treatments. Additionally, the combination reduced severe asthma risks by up to 46% in some cases. This evidence suggests that the budesonide/albuterol inhaler could be a strong option for managing asthma symptoms. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adolescents aged 12 to under 18 with asthma, who've had a severe asthma attack in the past year. They must be on stable asthma maintenance therapy for at least 3 months and demonstrate proper inhaler use without spacers. Participants need to perform reliable peak flow measurements and agree to specific contraception methods if applicable.

Inclusion Criteria

I have been diagnosed with asthma for over a year.

Receiving one of the following scheduled asthma maintenance therapies for at least 3 months with stable dosing for at least the last one month: Low-to-high-dose Inhaled corticosteroid(s) (ICS), Low-to-high-dose ICS with or without long-acting β2-agonist (LABA) and one additional maintenance therapy from the following: leukotriene receptor antagonist (LTRA), long-acting muscarinic antagonist (LAMA), or theophylline, Receiving inhaled short-acting β2-agonist (SABA) as needed, A documented history of at least one severe asthma exacerbation within 12 months, Use of Sponsor-provided albuterol sulfate inhalation aerosol medication, Demonstrate acceptable MDI administration technique as assessed by the investigator; use of spacers is prohibited, Able to perform acceptable and reproducible peak expiratory flow (PEF) measurements as assessed by the investigator, Participants must adhere to protocol specific contraception methods, Negative urine pregnancy test for participants of childbearing potential, Have a BMI < 40 kg/m^2, Capable of giving assent (signing the assent form) to participate in the study which includes compliance with the requirements and restrictions. The caregiver of the patient must be capable of giving written informed consent for the patient's participation in the study. Consent and assent forms must be completed prior to any study-specific procedures.

Exclusion Criteria

Life-threatening asthma defined as any history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s), Experienced > 3 severe asthma exacerbations within 12 months before screening, Completed treatment for lower respiratory infection and severe asthma exacerbation with SCS within 4 weeks of screening, Upper respiratory infection involving antibiotic treatment not resolved, Current smokers, former smokers with > 10 pack-years history, or former smokers who stopped smoking < 6 months (including all forms of tobacco, e-cigarettes [vaping], and marijuana), Other significant lung disease, including regular or occasional use of oxygen, Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neuropsychological, endocrine, or gastrointestinal disorders, Cancer not in complete remission for at least 5 years, History or hospitalization for psychiatric disorder or attempted suicide within one year, Significant abuse of alcohol or drugs, in the opinion of the investigator, Oral corticosteroid(s) (OCS)/SCS use (any dose and any indication) within 4 weeks before Visit 1 or chronic use of OCS/SCS (≥ 3 weeks use in 3 months prior to Visit 1), Use of any oral SABAs within one month, Having a known or suspected hypersensitivity to albuterol/salbutamol, or budesonide and/or their excipients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 to 4 weeks

Treatment

Participants receive either BDA MDI or AS MDI as needed for asthma management

52 weeks

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

1 to 2 weeks

Pharmacokinetic Sub-study

Single dose of open-label BDA MDI administered to assess pharmacokinetics

What Are the Treatments Tested in This Trial?

Interventions

• Albuterol Sulfate Metered-Dose Inhaler
• Budesonide/Albuterol Metered-Dose Inhaler

Trial Overview The study aims to compare two inhalers: BDA MDI (a combination of budesonide and albuterol) versus AS MDI (albuterol alone), used as needed during severe asthma attacks. It will assess which treatment better prevents exacerbations in young people with a history of serious asthma flare-ups.

How Is the Trial Designed?

Group I: Budesonide/albuterol metered -dose inhaler (BDA MDI) Experimental Treatment 1 Intervention

Participants will receive BDA MDI 160/180 μg (given as 2 puffs of 80/90 μg) as needed.

Group II: Albuterol sulfate metered-dose inhaler (AS MDI) Active Control 1 Intervention

Participants will receive AS MDI 180 μg (given as 2 puffs of 90 μg) as needed.

Budesonide/Albuterol Metered-Dose Inhaler is already approved in United States for the following indications:

Approved in United States as Airsupra for:

• Asthma
• Prevention of asthma attacks

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

In the phase 3 DENALI trial involving 1,001 patients with mild-to-moderate asthma, the combination of albuterol and budesonide significantly improved lung function compared to budesonide alone, demonstrating that both components contribute to the efficacy of the treatment.

The albuterol-budesonide combination was well tolerated over 12 weeks, with a safety profile similar to that of the individual components, supporting its potential as an effective rescue therapy for asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albuterol-Budesonide Pressurized Metered Dose Inhaler in Patients With Mild-to-Moderate Asthma: Results of the DENALI Double-Blind Randomized Controlled Trial. Chipps, BE., Israel, E., Beasley, R., et al.[2023]

In an 8-week clinical trial involving 24 patients, budesonide delivered via a dry-powder inhaler was found to be more effective than beclomethasone dipropionate given through a metered dose inhaler in reducing asthma symptoms and improving lung function tests.

Both medications were well tolerated with no adverse events reported, indicating that they are safe options for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single blinded randomised trial to compare the efficacy and safety of once daily budesonide (400microg) administered by turbuhaler with beclomethasone dipropionate (400microg) given twice daily through a metered-dose inhaler in patients with mild to moderate asthma. Ige, OM., Sogaolu, OM.[2013]

In a study involving 28 patients with stable bronchial asthma, inhaled budesonide delivered via the Turbuhaler showed significantly better effects on morning peak flow and resulted in fewer coughs immediately after inhalation compared to the pressurized metered dose inhaler (MDI).

Overall, budesonide via Turbuhaler was found to be at least as effective and safe as the MDI, with patients expressing a strong preference for the Turbuhaler device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler. Engel, T., Heinig, JH., Malling, HJ., et al.[2019]

Airsupra, a new asthma medication, effectively combines albuterol (a short-acting bronchodilator) with budesonide (a corticosteroid) to manage acute asthma attacks.

Patients are advised to continue their regular asthma maintenance therapy even when using Airsupra, ensuring comprehensive asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Combination Asthma Drug. Aschenbrenner, DS.[2023]

In a study involving 40 adult asthmatics, the pressurized metered-dose inhaler (pMDI) with extra-fine particles (FORM/BDP) showed a greater improvement in lung function compared to the pMDI with non-extra-fine particles (FORM/BUD), although overall treatment outcomes were similar between the two.

Patient preferences indicated that while FORM/BDP was perceived to have a higher flume velocity and was more effective in reaching the trachea and bronchus, it also caused more irritation than FORM/BUD, highlighting the importance of patient experience in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Two pMDIs in Adult Asthmatics: A Randomized Double-Blind Double-Dummy Clinical Trial. Nam, TH., Kang, SY., Lee, SM., et al.[2022]

In a 52-week study involving 708 patients with moderate to severe asthma, the combination of budesonide/formoterol showed a significantly lower rate of asthma exacerbations compared to budesonide alone, indicating improved efficacy in asthma management.

The safety profile of budesonide/formoterol was acceptable, with no significant differences in adverse events or clinical abnormalities compared to budesonide, suggesting that adding a long-acting beta(2)-adrenergic agonist (LABA) to inhaled corticosteroids (ICSs) is safe for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and asthma control with budesonide/formoterol versus budesonide pressurized metered-dose inhaler in asthma patients. Peters, SP., Prenner, BM., Mezzanotte, WS., et al.[2022]

Budesonide/formoterol 160/4.5 µg, administered as two inhalations twice daily, has shown significant efficacy in improving lung function and reducing respiratory symptoms in patients with severe chronic obstructive pulmonary disease (COPD) over 6 and 12 months in randomized controlled trials.

The combination treatment not only outperformed its individual components but also demonstrated a satisfactory safety profile, with no increased risk of pneumonia compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide and formoterol in a single pressurized metered-dose inhaler for treatment of COPD. Tashkin, DP.[2015]

In a study involving 3132 patients with uncontrolled moderate-to-severe asthma, the fixed-dose combination of albuterol and budesonide significantly reduced the risk of severe asthma exacerbations by 26% compared to albuterol alone.

The safety profile was similar across all treatment groups, indicating that the combination therapy is not only more effective but also safe for patients already on inhaled glucocorticoid maintenance therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma. Papi, A., Chipps, BE., Beasley, R., et al.[2023]

The study evaluated the efficacy of a fixed-dose combination rescue inhaler containing albuterol and budesonide for asthma management, demonstrating improved control of asthma symptoms compared to standard treatments.

In a large clinical trial, the combination inhaler was found to provide effective relief during asthma attacks while also reducing the need for additional rescue medication, indicating its potential as a safer and more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In moderate-to-severe asthma, as-needed albuterol-budesonide reduced severe exacerbations vs. albuterol alone. Confalonieri, M.[2022]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2203163

Albuterol–Budesonide Fixed-Dose Combination Rescue ... The annualized rate of severe asthma exacerbations was 0.43 (95% CI, 0.33 to 0.58) in the higher-dose combination group and 0.58 (95% CI, 0.44 to 0.77) in the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11898224/

Albuterol-Budesonide Pressurized Metered Dose Inhaler in ... In MANDALA, as-needed albuterol-budesonide 180/160 μg pMDI significantly reduced the risk of severe exacerbations by 27% compared with as-needed use of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06307665?term=NCT06307665&rank=1

Study Details | NCT06307665 | Evaluating the Efficacy and ... The purpose of this study is to compare the effect of budesonide/albuterol metered-dose inhaler (BDA MDI) with albuterol sulfate metered-dose inhaler (AS MDI), ...

4. pharmacytimes.com pharmacytimes.com/view/albuterol-budesonide-label-updated-to-include-clinically-meaningful-evidence-from-batura-study

Albuterol/Budesonide Label Updated to Include Clinically ... Albuterol/budesonide significantly reduces severe exacerbation risk in mild asthma by 46% compared with albuterol alone, as shown in the BATURA ...

5. rethinkingasthmarescue.com rethinkingasthmarescue.com/exacerbation-study/mandala-study.html

MANDALA Exacerbation Study There were 324 severe exacerbations in the albuterol/budesonide 180/160 mcg group and 403 in the albuterol group.1. ‖Mean annualized doses of SCS were rounded ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/214070s000lbl.pdf

AIRSUPRA (albuterol an - accessdata.fda.gov The recommended dosage of AIRSUPRA is albuterol 180 mcg and budesonide 160 mcg (administered as. 2 actuations of AIRSUPRA [albuterol/budesonide 90 mcg/80 mcg]) ...

7. airsuprapayer.com airsuprapayer.com/clinical-value-profile-of-airsupra

Clinical Value Profile | AIRSUPRA Inhalation Aerosol A Study to Assess the Efficacy and Safety of Budesonide/Albuterol Metered Dose Inhaler (BDA MDI/PT027) Used 4 Times Daily (DENALI).