Beta-Agonist Inhalers for Healthy Subjects

Overseen By Andrew R Brotto, MSc

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alberta

Must not be taking: Antidepressants, Beta-blockers, Steroids, others

Disqualifiers: Cardiac conditions, Diabetes, Respiratory disease, 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: 6

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how asthma inhalers affect the blood vessels and heart in healthy young adults. The researchers aim to determine if long-term use of these inhalers impacts the cardiovascular system. Participants will use an inhaler for four weeks and undergo various tests, including lung function assessments and ultrasound imaging of their arm artery. The trial compares two inhalers, Ventolin (salbutamol) and Symbicort (budesonide/formoterol), with a placebo to identify any differences. Healthy individuals without a history of heart or lung disease may be suitable for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants an opportunity to contribute to foundational medical knowledge.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications to participate in this trial. The trial excludes participants who are using specific medications like monoamine oxidase inhibitors, tricyclic antidepressants, beta-blockers, and several others.

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

Research shows that both budesonide-formoterol and salbutamol inhalers are generally well-tolerated by most people. Budesonide-formoterol is often used for asthma and chronic obstructive pulmonary disease (COPD). Studies have confirmed its safety, with no new safety concerns in patients with mild asthma.

Salbutamol, also known as Ventolin, has been tested in various trials with over 248 participants. It is generally considered safe but can cause some side effects, such as palpitations (a feeling of a rapid heartbeat) or a fast heart rate.

Both treatments have long been used to help with breathing problems and are FDA-approved for these uses, indicating a strong safety record for these conditions. However, since this trial is in an early phase, it is specifically designed to carefully test safety in healthy individuals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore different ways to use inhalers, even for those without respiratory issues. Budesonide/formoterol is unique as it combines a steroid with a long-acting beta-agonist, potentially providing prolonged relief and reducing inflammation. Salbutamol, another focus, is a fast-acting bronchodilator that quickly opens airways, which could be beneficial even for short-term usage in healthy individuals. This trial helps understand how these treatments might enhance respiratory function or be used in new ways beyond traditional asthma or COPD treatment.

What evidence suggests that this trial's treatments could be effective for blood vessel health?

This trial will compare the effects of different inhalers on healthy individuals. Research has shown that inhalers like Symbicort, which contain budesonide and formoterol, can improve lung function in people with asthma over time. One study found that 97% of patients felt relief within minutes of using it, indicating significant benefits for lung performance. In this trial, some participants will receive budesonide-formoterol.

Another group will receive salbutamol, often used for quick asthma relief. Studies have found that salbutamol can increase heart rate and blood pressure in healthy people. However, it did not enhance exercise performance in those without asthma, suggesting it may not improve lung function for non-asthmatic individuals.

A placebo group will also be included to compare the effects of these treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Tracey Bryan, MD

Principal Investigator

University of Alberta

Michael K Stickland, PhD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for healthy individuals aged 18-40 without heart or lung diseases. Participants should not be using medical inhalers, have abnormal exercise test results, pre-existing cardiac conditions, or be pregnant/lactating. Women must use contraception if they can bear children.

Exclusion Criteria

I have abnormal lung or heart test results, like low lung function, fast heart rate, or high blood pressure.

I am not taking specific medications like MAOIs, beta-blockers, or steroids.

Absolute contraindication to exercise testing or an orthopedic condition that may limit exercise testing as identified by standardized health screening tool (PAR-Q+).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessments including pulmonary function testing, cardiopulmonary exercise testing, and cardiovascular function measurements.

1 week

2 visits (in-person)

Treatment

Participants use an inhaler for 4 weeks and complete weekly symptom questionnaires.

4 weeks

Home use with electronic monitoring

Post-Treatment Assessment

Participants replicate baseline assessments to evaluate the impact of the inhaler use.

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment.

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Budesonide/formoterol
• Placebo
• Salbutamol

Trial Overview The study tests the effects of two asthma inhalers (Ventolin and Symbicort) versus a placebo on blood vessels over four weeks in young adults. It involves lung function tests, exercise tests, ultrasound imaging of an artery, and multiple lab visits.

How Is the Trial Designed?

Group I: Salbutamol Experimental Treatment 1 Intervention

Participants are healthy and between the ages of 18-40 years old

Group II: Budesonide-formoterol Experimental Treatment 1 Intervention

Participants are healthy and between the ages of 18-40 years old

Group III: Placebo Placebo Group 1 Intervention

Participants are healthy and between the ages of 18-40 years old

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

Approved in European Union as Symbicort for:

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)

Approved in United States as Symbicort for:

• Asthma
• COPD

Approved in Canada as Symbicort for:

• Asthma
• COPD

Approved in Japan as Symbicort for:

• Asthma
• COPD

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Published Research Related to This Trial

Budesonide formoterol (BF) Spiromax® is pharmacokinetically equivalent to BF Turbohaler®, as demonstrated in two studies with 90 healthy volunteers each, showing similar absorption and peak drug concentrations for both inhalers.

Both inhalers were well tolerated, with only a few minor treatment-emergent adverse events reported, indicating that BF Spiromax is a safe alternative to BF Turbohaler.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of budesonide plus formoterol (BF) Spiromax® and BF Turbohaler® (with and without charcoal block) in healthy volunteers. Weisfeld, L., Shu, Y., Shah, TP.[2015]

In a study of 467 adults with mild-to-moderate asthma, using a single inhaler of low-dose budesonide/formoterol significantly improved morning peak expiratory flow (PEF) compared to a higher dose of budesonide alone, with increases of 16.5 L/min versus 7.3 L/min.

The combination therapy also led to a 26% reduction in the risk of asthma exacerbations and improved the number of symptom-free days and asthma-control days, while showing similar safety profiles between the two treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide and formoterol in a single inhaler improves asthma control compared with increasing the dose of corticosteroid in adults with mild-to-moderate asthma. Lalloo, UG., Malolepszy, J., Kozma, D., et al.[2019]

In a study of 1,022 COPD patients, the combination of inhaled budesonide/formoterol significantly improved lung function and quality of life compared to placebo, with a notable increase in FEV1 and a reduction in health-related quality of life scores.

Patients using budesonide/formoterol experienced fewer exacerbations and a longer time to the first exacerbation, demonstrating that this combination therapy is more effective than using either medication alone or a placebo in maintaining lung function over 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Calverley, PM., Boonsawat, W., Cseke, Z., et al.[2022]

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 study involving 493 asthma patients, those using the DuoResp® Spiromax® inhaler achieved mastery of inhaler technique more effectively (94%) compared to those using the Symbicort® Turbuhaler® (87%), indicating that Spiromax may be easier to use.

While both inhalers improved asthma control, the long-term maintenance of inhaler mastery after 12 weeks was similar for both devices; however, an independent expert review showed that patients using Spiromax had significantly higher verified mastery levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of inhaler technique and achievement and maintenance of mastery of budesonide/formoterol Spiromax® compared with budesonide/formoterol Turbuhaler® in adult patients with asthma: the Easy Low Instruction Over Time (ELIOT) study. Price, DB., Thomas, V., Richard Dekhuijzen, PN., et al.[2019]

In a study of 207 patients with acute asthma, budesonide/formoterol (Symbicort) showed similar efficacy to salbutamol in improving lung function (FEV1) after treatment, with both showing about a 30% increase from baseline.

Budesonide/formoterol had a better safety profile, as it resulted in a lower mean pulse rate compared to salbutamol, indicating less cardiovascular stimulation, while both treatments were well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of budesonide/formoterol compared with salbutamol in the treatment of acute asthma. Balanag, VM., Yunus, F., Yang, PC., et al.[2015]

Combination inhalers like Seretide (salmeterol + fluticasone) and Symbicort (formoterol + budesonide) are recommended for patients with mild asthma who do not achieve adequate control with standard inhaled corticosteroids and short-acting beta 2-agonists.

These combination treatments are effective for both patients who are not well-controlled on existing therapies and those who are already stable on inhaled corticosteroids and long-acting beta 2-agonists, highlighting their versatility in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[symbol: see text] Seretide and [symbol: see text] Symbicort in asthma management. [2017]

In a study of 908 patients with persistent asthma, budesonide/formoterol (Symbicort SMART) was found to be as effective as conventional best practice (CBP) in preventing severe asthma exacerbations, with no significant difference in exacerbation rates between the two groups.

The Symbicort SMART regimen allowed for a significantly lower daily dose of inhaled corticosteroids (ICS) and reduced monthly drug costs compared to CBP, while also improving asthma control as measured by the Asthma Control Questionnaire.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of budesonide/formoterol maintenance and reliever therapy vs. conventional best practice in asthma management. Louis, R., Joos, G., Michils, A., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40956480/

A United Kingdom General Practice Cohort Study Patients who continued initiation treatment for a year without interruption had reduced exacerbation rates with FF/VI versus BUD/FOR.

2. symbicorttouchpoints.com symbicorttouchpoints.com/asthma-clinical-trials.html

Asthma Clinical Trial Data for SYMBICORT® (budesonide ... Sustained improvement in lung function was demonstrated in asthma patients ≥12 years of age in a 12-week efficacy and safety study.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1386666/

Budesonide/formoterol and formoterol provide similar rapid ... After 3 minutes, 97% of patients receiving budesonide/formoterol considered their medication to be effective; this figure remained at 97% at 15 minutes. The ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01386996?term=BUDESONIDE%20AND%20FORMOTEROL&rank=3

Comparison of Budesonide and Formoterol Absorption ... Evidence of a clinically significant cardiovascular, renal, hepatic, haematological, GI, pulmonary, metabolic-endocrine, neurological or psychiatric disease.

5. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2836268

Budesonide-Formoterol Metered-Dose Inhaler vs ... These results suggest that there was an increase in adverse health outcomes after the shift from budesonide-formoterol metered-dose inhaler therapy to ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2009/021929s012lbl.pdf

SYMBICORT (budesonide/formoterol fumarate dihydrate) Patients 12 years and older. The overall safety data in adults and adolescents are based upon 10 active- and placebo-controlled clinical trials in which. 3393 ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/budesonide-and-formoterol-inhalation-route/description/drg-20068949

Budesonide and formoterol (inhalation route) - Side effects ... Safety and efficacy have not been established. ... However, elderly patients with heart problems may require special caution when receiving budesonide and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7994217/

Safety of As-Needed Budesonide-Formoterol in Mild Asthma Budesonide-formoterol anti-inflammatory reliever therapy is generally well-tolerated in patients with mild asthma. No new safety concerns were ...

9. symbicorttouchpoints.com symbicorttouchpoints.com/

SYMBICORT® (budesonide/formoterol fumarate dihydrate ... Sustained improvement in lung function was demonstrated in a 12-month efficacy and safety study in COPD and a 12-week efficacy and safety study in asthma.3-6. † ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/021929s021lbl.pdf

Symbicort - accessdata.fda.gov SYMBICORT. Absorption: Budesonide: Healthy Subjects: Orally inhaled budesonide is rapidly absorbed in the lungs and peak concentration is typically reached ...