Budesonide + Formoterol Inhaler for Asthma

(VATHOS Trial)

No longer recruiting at 135 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: ICS or ICS/LABA

Disqualifiers: Life-threatening asthma, Respiratory infection, Cardiovascular disease, Drug abuse, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new inhaler that combines budesonide (a corticosteroid) and formoterol (a long-acting bronchodilator) to evaluate its effectiveness for people whose asthma isn't well-controlled by their current treatment. The goal is to determine the inhaler's effectiveness and safety over 24 weeks. Participants will join different groups to compare this new inhaler with other treatments. Suitable candidates have had asthma for at least six months and find their current inhaler insufficient for symptom control. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking asthma therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be willing to adjust your asthma therapy as required by the study protocol. You should discuss your specific medications with the study team to understand any necessary changes.

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

Research has shown that combining budesonide and formoterol is generally safe for people with asthma. Studies have found that this inhaler controls asthma symptoms better than using each medicine alone or a placebo. It also results in fewer asthma flare-ups compared to treatments like fluticasone-salmeterol.

For the budesonide inhaler alone, research suggests it is safe and effective. It improves asthma symptoms both during the day and at night. Users of budesonide have reported fewer emergency room visits and hospital stays.

These inhalers are being tested in the later stages of clinical trials, indicating existing evidence of their safety for humans. However, like any treatment, side effects may occur, so discussing any concerns with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for asthma because they offer potential improvements in inhaler therapy. Unlike the standard of care, which often includes separate inhalers for budesonide and formoterol, the Budesonide/Formoterol Fumarate (BFF) inhaler combines both medications into a single metered-dose inhaler, simplifying treatment. This combination inhaler is available in different dosage strengths (160/9.6 μg and 320/9.6 μg), allowing for flexibility based on patient needs. Additionally, the use of a metered-dose inhaler could provide a more precise and consistent delivery of medication compared to some current inhalers, potentially enhancing efficacy and reducing asthma symptoms more effectively.

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

Research has shown that using an inhaler with both budesonide and formoterol fumarate greatly improves asthma control compared to using each one alone or a placebo. In this trial, participants may receive the BFF MDI 320/9.6 μg dose, which studies have found particularly effective in controlling asthma symptoms. Another arm of the trial will test Budesonide MDI 320 μg alone, which has also proven to improve symptoms and reduce the need for extra medication. Strong clinical evidence supports both treatments, demonstrating their effectiveness in managing asthma. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

Adults and adolescents aged 12-80 with poorly controlled asthma, stable on inhaled corticosteroids or combination therapy for at least 8 weeks. Must have a history of asthma for over 6 months, non-smokers or those who quit smoking more than 6 months ago, not pregnant or breastfeeding, without life-threatening asthma events or recent hospitalizations.

Inclusion Criteria

I am between 12 and 80 years old, my BMI is under 40, and if female, I am not able to have children or am using effective birth control.

eDiary compliance ≥ 70% during screening, defined as completing the daily eDiary and answering 'Yes' to taking 2 puffs of run-in BD MDI for any 10 mornings and 10 evenings in the last 14 days prior to randomization

I have been diagnosed with asthma for at least 6 months.

Exclusion Criteria

Previous or current randomization into studies within the AEROSPHERE program including KALOS, LOGOS, VATHOS, LITHOS, or any glycopyrronium studies (PT001)

My cancer cannot be removed by surgery and has not been fully gone for 5 years.

Participation in another clinical study with a study intervention administered in the last 30 days or 5 half-lives, whichever is longer. Any other study intervention that is not identified in this protocol is prohibited for use during study duration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Budesonide and Formoterol Fumarate MDI or comparator treatments for asthma control

24 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Budesonide
• Formoterol Fumarate

Trial Overview The trial is testing different doses of Budesonide and Formoterol Fumarate Metered Dose Inhaler (BFF MDI) against an open-label Symbicort inhaler to see which is better at controlling asthma symptoms over a period of 24 weeks.

How Is the Trial Designed?

Group I: BFF MDI 320/9.6 μg Experimental Treatment 1 Intervention

Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 320/9.6 μg

Group II: BFF MDI 160/9.6 μg Experimental Treatment 1 Intervention

Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg

Group III: BD MDI 320 μg Experimental Treatment 1 Intervention

Budesonide MDI (BD MDI), 320 μg

Group IV: Open-label Symbicort TBH 320/9 μg Active Control 1 Intervention

Open-Label Comparator Symbicort Turbuhaler 320/9 μg

Budesonide is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Pulmicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis
• Crohn's disease
• Ulcerative colitis
• Microscopic colitis
• Eosinophilic esophagitis
• Primary immunoglobulin A nephropathy

Approved in United States as Entocort EC for:

• Crohn's disease
• Ulcerative colitis
• Primary immunoglobulin A nephropathy
• Eosinophilic esophagitis

Approved in Canada as Pulmicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis

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

Published Research Related to This Trial

Symbicort, a combination inhaler for asthma and COPD, is more cost-effective than using separate inhalers for its components, budesonide and formoterol, as it leads to lower total treatment costs.

The adjustable dosing strategy of Symbicort not only maintains better asthma control with less medication but also reduces overall treatment costs compared to fixed dosing and other combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symbicort: a pharmacoeconomic review. Halpin, DM.[2018]

In a long-term safety trial involving 896 patients with rheumatoid arthritis, tacrolimus at a dose of 3 mg/day was found to be safe and well-tolerated over a median treatment duration of 359 days, with no new adverse events appearing after the first 3 months.

The treatment resulted in significant clinical benefits, with ACR20, ACR50, and ACR70 response rates of 38.4%, 18.6%, and 9.0% respectively, indicating that over 26% of patients experienced at least a 70% improvement in joint symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of tacrolimus in patients with rheumatoid arthritis: long-term experience. Yocum, DE., Furst, DE., Bensen, WG., et al.[2019]

In a study of 373 patients with moderate persistent asthma, Symbicort (budesonide/formoterol) significantly improved lung function compared to fluticasone propionate, with greater increases in morning peak expiratory flow (PEF) and fewer asthma exacerbations.

Symbicort also led to better overall asthma control, as indicated by a higher percentage of symptom-free days and reduced reliance on reliever medication, while both treatments were well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with single inhaler budesonide/formoterol compared with high dose of fluticasone propionate alone in patients with moderate persistent asthma. Bateman, ED., Bantje, TA., João Gomes, M., et al.[2019]

The fixed combination of budesonide and formoterol fumarate dihydrate is an effective treatment option for asthma in adolescents and adults, providing both maintenance and reliever therapy in a single inhaler, which enhances convenience for patients.

This combination therapy has been shown to reduce the frequency of asthma exacerbations that require oral corticosteroids, although more research is needed to confirm its impact on serious outcomes like hospital admissions and emergency visits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide + formoterol fumarate dihydrate for the treatment of asthma. Wolthers, OD.[2018]

In a study of 57 elderly patients with rheumatoid arthritis who did not respond adequately to DMARDs, tacrolimus was found to be safe and well-tolerated, with 46.3% experiencing clinical adverse events and 18.5% developing infections.

Tacrolimus treatment resulted in a 50% response rate according to the ACR20 criteria, indicating that half of the patients showed significant improvement in their symptoms over 28 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of tacrolimus, an immunosuppressive agent, in the treatment of rheumatoid arthritis in elderly patients. Kawai, S., Yamamoto, K.[2013]

In a Phase 3 study involving 279 patients with moderate to severe asthma, fluticasone/formoterol was found to be as effective as budesonide/formoterol in improving lung function, measured by the change in pre-dose FEV₁ over 12 weeks.

Both treatments demonstrated a similar safety profile, indicating that fluticasone/formoterol is a viable alternative to budesonide/formoterol for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluticasone/formoterol combination therapy versus budesonide/formoterol for the treatment of asthma: a randomized, controlled, non-inferiority trial of efficacy and safety. Bodzenta-Lukaszyk, A., Buhl, R., Balint, B., et al.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9819296/

Efficacy and safety of budesonide inhalation suspension ... All doses of budesonide inhalation suspension were superior to placebo in improving nighttime and daytime asthma symptom scores (P </=. 026), reducing use of ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291802800054

Efficacy of budesonide in moderate to severe asthma Results: Budesonide is associated with a dose-response effect in adults and children with moderate to severe asthma. The data on budesonide are in line with the ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1901963

Controlled Trial of Budesonide–Formoterol as Needed for ... In an open-label trial involving adults with mild asthma, budesonide–formoterol used as needed was superior to albuterol used as needed for the prevention of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8713049/

Budesonide at different doses for chronic asthma Budesonide exhibits a significant dose response effect between low and high dose for improvement in FEV1 in severe asthma and reduction of exacerbations in ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/02770903.2024.2334897

Full article: Expert panel consensus recommendations on ... Nebulized budesonide is effective and well-tolerated in treating asthma and COPD, with less systemic adverse effects compared to systemic corticosteroids. High- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11730512/

Comparative analysis of real-world data on the efficacy and ... Outcomes assessed included treatment adherence, asthma exacerbations, hospitalizations, emergency-department visits, mortality, and safety ...

7. jacionline.org jacionline.org/article/S0091-6749(98)70019-3/fulltext

Efficacy and safety of budesonide inhalation suspension ... The results of this study demonstrate that budesonide inhalation suspension 0.25 to 1.0 mg twice daily is safe and effective for the treatment of steroid- ...