Budesonide + Formoterol Inhaler for Asthma

(VATHOS Trial)

Recruiting at 125 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

644 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests an inhaler that combines two medications to help people with poorly controlled asthma. It aims to see if this new inhaler can better manage their symptoms by reducing inflammation and keeping airways open. Combination products often have useful clinical benefits in asthma. The scientific rationale for combination therapy includes the fact that different agents have complementary modes of action.

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.

What data supports the effectiveness of the drug Budesonide + Formoterol Inhaler for Asthma?

Research shows that the combination of budesonide and formoterol in a single inhaler (Symbicort) is effective in reducing asthma exacerbations and improving lung function compared to using budesonide alone. It also provides rapid relief for acute asthma symptoms and is as effective as other similar combination therapies. ^{1 2 3 4 5}

Is the Budesonide inhalation suspension safe for children with asthma?

In a study of children with asthma, Budesonide inhalation suspension was found to be safe, with similar rates of mild adverse events like fever and injection-site reactions compared to other asthma treatments. ^{6 7 8 9 10}

What makes the drug Budesonide + Formoterol unique for treating asthma?

Budesonide + Formoterol is unique because it combines an inhaled corticosteroid (budesonide) with a long-acting bronchodilator (formoterol) in a single inhaler, allowing it to be used both for regular maintenance and as a quick-relief therapy during asthma attacks, which can help reduce exacerbations more effectively than fixed-dose regimens. ^{2 3 5 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Budesonide/formoterol and formoterol provide similar rapid relief in patients with acute asthma showing refractoriness to salbutamol. [2018]

2. England 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. [2015]

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

Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma. [2015]

4. New Zealand 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. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Inhibitory effect of budesonide alone and in combination with formoterol on IL-5 and RANTES production from mononuclear cells. [2015]

6. India pubmed.ncbi.nlm.nih.gov

Antibody response after varicella vaccination in children treated with budesonide inhalation suspension or non-steroidal conventional asthma therapy. [2006]

7. England pubmed.ncbi.nlm.nih.gov

Safety of tacrolimus in patients with rheumatoid arthritis: long-term experience. [2019]

8. Denmark pubmed.ncbi.nlm.nih.gov

Neoral rescue therapy in transplant patients with intolerance to tacrolimus. [2019]

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

Clinical Effectiveness and Safety of Treatment With Anti-Tumor Necrosis Factor α Drugs in a Cohort of Colombian Patients With Rheumatoid Arthritis. [2021]

10. England pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

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

12. England pubmed.ncbi.nlm.nih.gov

Symbicort: a pharmacoeconomic review. [2018]