Advair HFA for Altitude Edema

(SWIFTARC Trial)

Overseen By James P Maloney, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Colorado, Denver

Must not be taking: Blood thinners, PDE-5 inhibitors

Disqualifiers: Impaired liver function, cardiovascular conditions, others

Compensation: Varies

Number of Visits: 2

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The current protocol is composed of two studies. The first study is designed to carefully evaluate the safety of high-dose salmeterol/fluticasone (Advair HFA) versus placebo (hydrofluoroalkane, HFA) administration over 7 days, as well as the efficacy of the study drug to increase exercise performance, in healthy individuals exercising under hypoxic, simulated high-altitude conditions (Phase 1/2a study). The second study will examine sensitive measures of cardiopulmonary function using invasive cardiopulmonary testing, in both HAPE-sensitive and HAPE-resistant individuals, to assess the potential efficacy of salmeterol/fluticasone to prevent pulmonary edema and to enhance exercise capacity (Phase 2a) in these individuals.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, including nonselective beta-blockers, inhaled or oral beta-2 receptor agonists, non-potassium sparing diuretics, and medications that strongly interact with the study drug. If you are on any of these, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug Advair HFA for treating altitude edema?

Research shows that the components of Advair HFA, fluticasone and salmeterol, are effective in improving lung function in conditions like asthma and COPD (chronic obstructive pulmonary disease). While this is not direct evidence for altitude edema, it suggests potential benefits in improving breathing-related issues. ^{1 2 3 4 5}

Is Advair HFA safe for humans?

Advair HFA, also known as Wixela Inhub or fluticasone/salmeterol, has been shown to be well tolerated in studies for asthma and chronic obstructive pulmonary disease (COPD). These studies indicate that the treatment is generally safe for human use, with similar safety profiles to its equivalent, Advair Diskus. ^{1 2 3 6 7}

How does the drug Advair HFA differ from other treatments for altitude edema?

Advair HFA is unique for altitude edema as it combines fluticasone (a corticosteroid that reduces inflammation) and salmeterol (a long-acting bronchodilator that helps open airways), typically used for asthma and COPD, but its use for altitude edema is novel since there are no standard treatments specifically for this condition. ^{2 3 6 8 9}

Research Team

James P Maloney, MD

Principal Investigator

Univ. of Colorado, Denver

Eligibility Criteria

This trial is for healthy individuals aged 18-50, with a BMI between 20 and <35. Participants must be in good health as confirmed by medical exams and tests, agree to follow the study's procedures, and have good veins for IVs. For part of the study, people either need a history of high-altitude pulmonary edema (HAPE) or no HAPE during high altitude exposure.

Inclusion Criteria

You agree to abide by the specified interventions and treatments for the entirety of the study.

In Study 2, you must have no evidence of HAPE when travelling to high altitude locations in Colorado and reside at or below 3,000 feet without acclimatization (e.g., as a travel partner with someone who is susceptible to HAPE).

I am in good health based on recent medical exams and tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Study 1)

Participants receive salmeterol/fluticasone or placebo for 7 days with exercise under hypoxic conditions and continuous cardiac monitoring

7 days

1 visit (in-person) for exercise testing

Washout

Participants undergo a washout period between crossover periods

7 days

Treatment (Study 2)

Participants receive salmeterol/fluticasone or placebo for 2 days prior to hypoxic exercise testing, with efficacy assessments including VO2 max and right heart catheter measurements

2 days

1 visit (in-person) for exercise testing

Follow-up

Participants are monitored for safety and effectiveness after treatment, including continuous cardiac monitoring and safety lab tests

5 days

Treatment Details

Interventions

• Advair HFA
• Placebo

Trial Overview The trial is testing Advair HFA against a placebo over seven days to see if it's safe and can improve exercise performance under simulated high-altitude conditions. It also looks at how well it prevents pulmonary edema and boosts exercise capacity in those prone or resistant to HAPE.

Participant Groups

Group I: Advair HFA (salmeterol 126 ug/fluticasone 270 ug) twice daily for up to 7 days Experimental Treatment 1 Intervention

Participants will inhale salmeterol 126 ug and fluticasone 270 ug twice daily for up to 7 days

Group II: Placebo Placebo Group 1 Intervention

Participants will inhale placebo (same puff number) twice daily for up to 7 days

Advair HFA is already approved in United States, European Union for the following indications:

Approved in United States as Advair HFA for:

• Asthma

Approved in European Union as Advair HFA for:

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)

Approved in United States as Wixela Inhub for:

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

MTEC

Collaborator

Trials

2

Recruited

110+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Wixela Inhub, a dry powder inhaler delivering fluticasone propionate and salmeterol, shows low flow dependency in delivering medication to severe COPD patients, ensuring consistent dosing across varying inhalation profiles.

The study found that both types of breathing simulators used produced similar results for fluticasone propionate, indicating reliability in dose delivery, while slight differences were noted for salmeterol, suggesting the need for further investigation into its delivery characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Performance of the Wixela Inhub Inhaler Using Severe Chronic Obstructive Pulmonary Disease Patient Inhalation Profiles. Shepherd, T., Kennett, M., Cooper, A., et al.[2023]

Wixela™ Inhub™ is a generic version of Advair Diskus® and has been shown to have comparable in vitro performance and clinical effectiveness in improving lung function for patients with asthma and COPD.

Bioequivalence studies confirm that Wixela Inhub delivers similar doses of fluticasone propionate and salmeterol as Advair Diskus, making it a viable treatment option for patients whose symptoms are not controlled by inhaled corticosteroids alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wixela Inhub: A Generic Equivalent Treatment Option for Patients with Asthma or COPD. Donohue, JF., Burgoyne, DS., Ward, JK., et al.[2021]

A study involving 1127 patients with mild-to-moderate asthma showed that Wixela Inhub (the generic version) and Advair Diskus (the brand name) have equivalent therapeutic effects on lung function, as measured by forced expiratory volume in 1 second (FEV1).

Both Wixela Inhub and Advair Diskus were well tolerated, indicating that Wixela Inhub is a safe and effective alternative for treating asthma and COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Bioequivalence of Wixela Inhub and Advair Diskus in Adults With Asthma. Ng, D., Kerwin, EM., White, MV., et al.[2021]

In a study of 100 patients with bronchial asthma, the combination of fluticasone and salmeterol dry powder demonstrated a significantly higher treatment efficacy compared to budesonide powder, with improved lung function and reduced inflammatory factors.

The treatment with fluticasone and salmeterol also had a lower incidence of adverse reactions, indicating a favorable safety profile that supports its use as a promising option for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Fluticasone and Salmeterol Dry Powder in Treating Patients with Bronchial Asthma and Its Effect on Inflammatory Factors and Pulmonary Function. Zhang, X., Liu, M., Mao, Y.[2023]

In a study of 274 asthmatic patients, adding salmeterol to a low or intermediate dose of fluticasone propionate resulted in significantly better lung function and symptom control compared to simply doubling the fluticasone dose over 12 weeks.

Patients receiving salmeterol experienced greater improvements in peak expiratory flow rates and symptom-free days, with no significant differences in adverse effects between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma. van Noord, JA., Schreurs, AJ., Mol, SJ., et al.[2019]

Wixela Inhub demonstrated pharmacokinetic bioequivalence to Advair Diskus for both fluticasone propionate (FP) and salmeterol across all tested doses (100/50, 250/50, and 500/50 μg) in a study involving 66 healthy subjects per dose, confirming its effectiveness as a generic alternative.

Both Wixela Inhub and Advair Diskus were well tolerated, indicating that Wixela Inhub not only matches the efficacy of Advair Diskus but also maintains similar safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equivalent Systemic Exposure to Fluticasone Propionate/Salmeterol Following Single Inhaled Doses from Advair Diskus and Wixela Inhub: Results of Three Pharmacokinetic Bioequivalence Studies. Haughie, S., Allan, R., Wood, N., et al.[2021]

In a study involving 514 adult patients with persistent asthma, both inhaled triamcinolone acetonide (TAA) formulations (HFA and P-12) showed significant improvements in asthma symptoms and lung function compared to placebo, with effects noticeable as early as 24 hours for peak expiratory flow and 1 week for lung function measurements.

Both TAA formulations demonstrated comparable safety profiles, with no significant differences in adverse events across treatment groups, indicating that both are effective and safe options for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled trial of chlorofluorocarbon-free triamcinolone acetonide inhalation aerosol in the treatment of adult patients with persistent asthma. Azmacort HFA Study Group. Welch, M., Bernstein, D., Gross, G., et al.[2019]

Wixela Inhub, a generic version of Advair Diskus, demonstrated comparable in vitro performance in delivering medication across various flow rates, confirming its effectiveness for treating asthma and COPD.

In a patient inhalation study involving 68 participants (40 children and 28 adults), Wixela Inhub showed acceptable inhalation profiles, with peak inhaled flow rates that, while slightly lower than those of Advair Diskus, did not affect its bioequivalence or substitutability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wixela Inhub: Dosing Performance In Vitro and Inhaled Flow Rates in Healthy Subjects and Patients Compared with Advair Diskus. Cooper, A., Parker, J., Berry, M., et al.[2021]

Wixela Inhub, a new generic inhaler combining fluticasone propionate and salmeterol, has been approved as a bioequivalent alternative to Advair Diskus, providing a cost-effective option for asthma and COPD treatment.

Combination therapy with inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs) is recommended for patients with uncontrolled asthma or moderate to severe COPD, highlighting the importance of effective management strategies for these chronic respiratory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of ICS/LABA Fixed-Dose Combinations in the Treatment of Asthma and COPD: Bioequivalence of a Generic Fluticasone Propionate-Salmeterol Device. Tashkin, DP., Ohar, JA., Koltun, A., et al.[2022]

References

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

In Vitro Performance of the Wixela Inhub Inhaler Using Severe Chronic Obstructive Pulmonary Disease Patient Inhalation Profiles. [2023]

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

Wixela Inhub: A Generic Equivalent Treatment Option for Patients with Asthma or COPD. [2021]

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

Clinical Bioequivalence of Wixela Inhub and Advair Diskus in Adults With Asthma. [2021]

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

Efficacy of Fluticasone and Salmeterol Dry Powder in Treating Patients with Bronchial Asthma and Its Effect on Inflammatory Factors and Pulmonary Function. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma. [2019]

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

Equivalent Systemic Exposure to Fluticasone Propionate/Salmeterol Following Single Inhaled Doses from Advair Diskus and Wixela Inhub: Results of Three Pharmacokinetic Bioequivalence Studies. [2021]

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

A controlled trial of chlorofluorocarbon-free triamcinolone acetonide inhalation aerosol in the treatment of adult patients with persistent asthma. Azmacort HFA Study Group. [2019]

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

Wixela Inhub: Dosing Performance In Vitro and Inhaled Flow Rates in Healthy Subjects and Patients Compared with Advair Diskus. [2021]

9. Egypt pubmed.ncbi.nlm.nih.gov

The Role of ICS/LABA Fixed-Dose Combinations in the Treatment of Asthma and COPD: Bioequivalence of a Generic Fluticasone Propionate-Salmeterol Device. [2022]