Inhaled Epinephrine for Allergic Reactions

Overseen By George H. Luciuk, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dr. George Luciuk

Must not be taking: Antihistamines, Bronchodilators

Disqualifiers: Cardiovascular, Respiratory, Uncontrolled asthma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this exploratory study is to evaluate the effects of inhaled epinephrine in patients with known or suspected metabisulfite sensitivity who experience a systemic allergic reaction (SAR) while undergoing allergy testing, immunotherapy or oral challenges.

Will I have to stop taking my current medications?

The trial requires that you stop using antihistamines 5 days before and bronchodilators 24 hours before the pre-challenge visit. Other medications are not specifically mentioned, so it's best to discuss with the study team.

What data supports the effectiveness of the drug inhaled epinephrine for allergic reactions?

Epinephrine is known to be effective as a first-line treatment for severe allergic reactions, and rapid administration is linked to better outcomes. The development of needle-free devices like intranasal sprays aims to make epinephrine more accessible and easier to use, potentially improving treatment speed and effectiveness in emergency situations. ^{1 2 3 4 5}

Is inhaled epinephrine safe for humans?

Inhaled epinephrine, such as Primatene Mist, has been studied for asthma and shows minimal safety concerns even at high doses. No significant adverse effects were found, indicating it is generally safe for human use. ^{1 2 4 6 7}

How does inhaled epinephrine differ from other drugs for allergic reactions?

Inhaled epinephrine offers a unique way to treat allergic reactions by delivering the medication directly to the lungs through inhalation, which can be easier and less intimidating than using an injection. This method is similar to how some asthma medications are administered, providing rapid relief with potentially fewer side effects compared to injected forms. ^{1 2 7 8 9}

Research Team

George H. Luciuk, MD

Principal Investigator

Kokua Pharma Inc.

Eligibility Criteria

Adults aged 18+ with known or suspected metabisulfite sensitivity and a history of systemic allergic reactions (SAR) during allergy testing, oral challenges, or immunotherapy can join. They must not be pregnant, breastfeeding, and willing to use birth control. Excluded are those sensitive to epinephrine, uncontrolled asthma/COPD patients, recent surgery recipients, individuals with severe health conditions as assessed by the investigator.

Inclusion Criteria

I've had a severe allergic reaction after allergy treatments or tests.

For females of child-bearing potential, not pregnant or lactating, willing to use a highly effective method of birth control between Screening and End-of-Study Visits

I am 18 or older with a known or suspected allergy to metabisulfite, confirmed by tests.

Exclusion Criteria

Known reaction or sensitivity to epinephrine or any of the ingredients of inhaled epinephrine

My asthma or COPD is not under control.

Previous treatment in this study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive inhaled epinephrine during allergy testing, immunotherapy, or oral challenges

1 week

Single visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Inhaled Epinephrine

Trial Overview The trial is exploring how inhaled epinephrine affects people who have had a moderate to severe allergic reaction while undergoing various allergy-related procedures like tests or immunotherapies.

Participant Groups

Group I: Inhaled Epinephrine Experimental Treatment 1 Intervention

The first inhalation will be administered as soon as possible (i.e., within approximately 30 seconds) following identification of a Grade 2 or greater SAR and confirmation of enrollment by the Principal Investigator. The second inhalation will be administered approximately 10 seconds later, and the subject will be observed for approximately 2 minutes for signs of symptom resolution. Inhalations will continue in this manner until either: 1. resolution of systemic symptoms (defined as a reduction in SAR Grade to ≤1), or 2. maximum number of inhalations (8 inhalations) is reached, or 3. administration of intra-muscular epinephrine, whichever occurs earlier

Who Is Running the Clinical Trial?

Dr. George Luciuk

Lead Sponsor

Trials

1

Recruited

60+

Findings from Research

The intranasal epinephrine delivery device, neffy, demonstrated a pharmacokinetic profile that falls between traditional injection methods, with a peak plasma level of 481 pg/mL, indicating it effectively delivers epinephrine.

Neffy produced stronger pharmacodynamic responses compared to EpiPen and manual injections, suggesting it could be a safer and more effective option for patients who find traditional injection devices cumbersome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics/pharmacodynamics of epinephrine after single and repeat administration of neffy, EpiPen, and manual intramuscular injection. Casale, TB., Ellis, AK., Nowak-Wegrzyn, A., et al.[2023]

Epinephrine HFA has shown to improve lung function in adults and children aged 12 and older with mild intermittent asthma symptoms, making it a potential effective nonprescription bronchodilator.

While no major safety concerns were identified during the review, there are significant worries about potential device malfunctions and inaccuracies in the dose-counter, which are critical for a medication used in life-threatening asthma situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonprescription Epinephrine Metered-Dose Inhaler: To Be or Not To Be. Blake, K., Raissy, H.[2022]

Innovative epinephrine delivery methods, such as nasal sprays and sublingual films, show promising pharmacokinetic results comparable to traditional intramuscular injections, potentially improving the emergency treatment of anaphylaxis.

These needle-free alternatives may enhance patient compliance and safety by addressing common barriers associated with epinephrine autoinjectors, such as fear of needles and ease of carriage, making them a viable option for outpatient use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovations in the treatment of anaphylaxis: A review of recent data. Lieberman, JA., Oppenheimer, J., Hernandez-Trujillo, VP., et al.[2023]

Epinephrine delivered via an intranasal spray (neffy) is absorbed more effectively during anaphylaxis with severe hypotension, showing higher maximum concentrations compared to normal conditions in a study involving 14 anesthetized beagle dogs.

The study indicates that despite the hypotension associated with severe allergic reactions, epinephrine absorption via neffy remains effective, suggesting it could be a reliable treatment option in emergency situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of anaphylaxis on the absorption of intranasal epinephrine in anaesthetized non-naive beagle dogs. Sparapani, S., Authier, S., Lowenthal, R., et al.[2023]

In a study involving eight patients with seasonal asthma, infusions of epinephrine significantly improved end expiratory flow rates, indicating its potential to dilate smaller airways and counteract allergen-induced bronchoconstriction.

Epinephrine allowed patients to tolerate higher doses of allergens without significant bronchoconstriction, but when bronchoconstriction did occur, it was less responsive to beta-2-agonist treatment, suggesting that while epinephrine can provide temporary relief, it may lead to more severe reactions when allergens are encountered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchodilatation and inhibition of allergen-induced bronchoconstriction by circulating epinephrine in asthmatic subjects. Larsson, K., Grönneberg, R., Hjemdahl, P.[2019]

Epinephrine HFA metered-dose inhaler (MDI) showed significant improvements in lung function (FEV1) for doses above 125 μg compared to placebo, indicating its efficacy in treating asthma.

The safety profile of epinephrine HFA MDI was favorable, with minimal safety concerns and no significant differences compared to the active control (epinephrine CFC MDI), supporting the use of doses between 125-250 μg for longer-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Dose-Ranging Study of Epinephrine Hydrofluroalkane Metered-Dose Inhaler (Primatene® MIST) in Subjects with Intermittent or Mild-to-Moderate Persistent Asthma. Kerwin, EM., Tashkin, DP., Murphy, TR., et al.[2021]

The new epinephrine HFA metered-dose inhaler (MDI) showed approximately 37% greater systemic drug exposure compared to the older CFC version, indicating it may be more effective in delivering epinephrine quickly.

Safety assessments revealed minimal adverse effects even at very high doses (up to 10 inhalations), suggesting that the epinephrine HFA MDI is safe for use in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Study of Epinephrine Hydrofluoroalkane (Primatene MIST) Metered-Dose Inhaler. Kerwin, EM., Marrs, T., Luo, MZ., et al.[2021]

In a pilot study involving 4 subjects with mild stable asthma, inhaled racepinephrine (RE) showed a significant dose-response effect, but provided less bronchoprotection compared to nebulized albuterol, indicating it may be less effective for treating acute bronchospasm.

The study found that the 10 mg dose of RE resulted in a provocative concentration of methacholine causing a 20% decrease in FEV1 of 10.2 mg/mL, compared to 44 mg/mL after albuterol, suggesting that while RE is available as a nonprescription option, it may not be as effective as albuterol for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonprescription racemic epinephrine for asthma. Mondal, P., Kandala, B., Ahrens, R., et al.[2015]

In patients with severe asthma (peak expiratory flow rate less than 120), subcutaneous epinephrine was significantly more effective than aerosol epinephrine after one hour, indicating its superior efficacy in acute situations.

For patients with mild to moderate asthma (peak expiratory flow rate greater than 120), both forms of epinephrine were equally effective, but aerosol epinephrine caused fewer side effects, suggesting it may be a safer option for less severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aerosol vs injected epinephrine in acute asthma. Pliss, LB., Gallagher, EJ.[2019]

References

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

Pharmacokinetics/pharmacodynamics of epinephrine after single and repeat administration of neffy, EpiPen, and manual intramuscular injection. [2023]

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

Nonprescription Epinephrine Metered-Dose Inhaler: To Be or Not To Be. [2022]

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

Innovations in the treatment of anaphylaxis: A review of recent data. [2023]

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

The impact of anaphylaxis on the absorption of intranasal epinephrine in anaesthetized non-naive beagle dogs. [2023]

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

Bronchodilatation and inhibition of allergen-induced bronchoconstriction by circulating epinephrine in asthmatic subjects. [2019]

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

A Dose-Ranging Study of Epinephrine Hydrofluroalkane Metered-Dose Inhaler (Primatene® MIST) in Subjects with Intermittent or Mild-to-Moderate Persistent Asthma. [2021]

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

Pharmacokinetic Study of Epinephrine Hydrofluoroalkane (Primatene MIST) Metered-Dose Inhaler. [2021]

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

Nonprescription racemic epinephrine for asthma. [2015]

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

Aerosol vs injected epinephrine in acute asthma. [2019]