Study of Drug Exposure in Systemic Circulation of Primatene Mist by Oral Inhalation, Versus Epinephrine Injection by Intramuscular Injection and ProAir by Oral Inhalation in Healthy Individuals

NCT ID: NCT04207840

Last Updated: 2021-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-09
• Study Completion Date: 2019-12-23

Brief Summary

To assess the drug exposure profile in systemic circulation of Primatene Mist by inhalation, versus Epinephrine by intramuscular injection, and ProAir HFA by inhalation in healthy adults.

Conditions

Pharmacokinetics; Epinephrine; Albuterol; Asthma; Anaphylaxis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Primatene Mist, E004

Participants who dosed with Primatene Mist.

Group Type: EXPERIMENTAL

Epinephrine (0.125 mg/inhalation)

Intervention Type: COMBINATION_PRODUCT

Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.

Epinephrine Injection Auto-Injector (Generic of EpiPen)

Participants who were dosed with an Epinephrine Injection Auto-Injector.

Group Type: ACTIVE_COMPARATOR

Epinephrine Injection Auto-Injector (0.3mg/0.3mL)

Intervention Type: COMBINATION_PRODUCT

Participants will receive an intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL). The 0.30 mL dose will be given perpendicularly as a single deep intramuscular injection into the anterolateral aspect of the thigh.

Albuterol HFA

Participants who dosed with Albuterol HFA.

Group Type: ACTIVE_COMPARATOR

Albuterol Sulfate (0.09 mg/inhalation)

Intervention Type: COMBINATION_PRODUCT

Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.

Interventions

Epinephrine (0.125 mg/inhalation)

Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.

Intervention Type: COMBINATION_PRODUCT

Epinephrine Injection Auto-Injector (0.3mg/0.3mL)

Participants will receive an intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL). The 0.30 mL dose will be given perpendicularly as a single deep intramuscular injection into the anterolateral aspect of the thigh.

Intervention Type: COMBINATION_PRODUCT

Albuterol Sulfate (0.09 mg/inhalation)

Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

Primatene Mist; Generic of EpiPen; Albuterol HFA

Eligibility Criteria

Inclusion Criteria

• Agree to participate; understand and sign informed consent;
• Male and female adults, aged 18 to 50 years, inclusive at Screening;
• Generally healthy and medically stable, with no clinically significant abnormalities based on physical examination and laboratory tests as determined by the Investigators;
• Have good venous access;
• Have normal resting blood pressure and normal heart rate (HR) without history of syncope; a subject with out of range blood pressure may be enrolled in the study at the discretion of the Principal Investigator;
• Have a body mass index (BMI) of 18.0 - 30.0 kg/m^2;
• Female candidates must be >1 year post-menopausal or practicing a clinically acceptable form of birth control and confirmed by negative urine or serum pregnancy test at Screening;
• Negative HIV-Ab, HBs-Ag and HCV-Ab;
• Negative alcohol test (urine or breathalyzer);
• Negative drug screening results;
• Currently non-smoker; have not used any tobacco products for at least three (3) months prior to Screening; and
• Demonstrate proficiency in the use of MDI and a consistent inhalation time >2.0 seconds after training, for at least three (3) times, with a maximum of 5 attempts.

Exclusion Criteria

• Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, or malignant diseases.
• Known intolerance or hypersensitivity to any component of the study drugs (i.e., Epinephrine, Albuterol Sulfate or any sympathomimetic drugs, HFA-134a, thymol, ethanol, ascorbic acid, nitric acid, and hydrochloric acid).
• Upper or lower respiratory tract infection, or other systemic infection within 6 weeks prior to Screening;
• Clinically significant abnormalities in the screening/baseline ECG; prolonged corrected QT interval (QTcF) on ECG: men >450ms, women: >470ms; single or multiple premature ventricular contractions (PVC);
• Abnormal thyroid function test (if TSH is out of range, refer to T3/T4 for thyroid function assessment);
• Subject has been on other investigational drug/device studies within 30 days of Screening Visit or planned participation in another investigational drug trial at any time during this trial;
• Women who are pregnant or lactating or planning a pregnancy during the study period;
• Subject has donated or lost > 500 mL of blood within 3 months of Screening;
• Evidence of alcohol or drug abuse or dependency within 6 months prior to screening; or
• Use of any of the prohibited drugs without appropriate washout.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Amphastar Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Amphastar Study Site 0035

Cypress, California, United States

Countries

United States

References

Zhang JY, Luo MZ, Marrs T, Kerwin EM, Bukstein DA. Comparison of Systemic Exposure Between Epinephrine Delivered via Metered-Dose Inhalation and Intramuscular Injection. J Aerosol Med Pulm Drug Deliv. 2025 Apr;38(2):71-82. doi: 10.1089/jamp.2024.0025. Epub 2024 Aug 29.

Reference Type: DERIVED

PMID: 39207239 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

API-E004-CL-I

Identifier Type: -

Identifier Source: org_study_id