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

NCT04207840 | Completed Phase 4 Results FDA Drug

• 1 other identifier: API-E004-CL-I
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (4)

• C[Max], Maximum Plasma Concentration of Albuterol or Epinephrine

  Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. C\[max\] will be obtained directly from the plot of PK curve.

  Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.

• AUC(0-tm)_TOT, Area Under the Curve (AUC) of Total (Exogenous and Endogenous, if Available) Active Product Ingredient (API) From Time 0 to Time (tm)

  Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. AUC(0-tm)\_TOT will be calculated with the trapezoid method. Time tm is defined as the time after C\[max\] is reached where API concentration is reduced to the levels of the same day baseline.

  Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.

• AUC(0-tm)_DE, Area Under the Curve (AUC) of Exogenous Active Product Ingredient (API) From Time 0 to Time (tm)

  Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. AUC(0-tm)\_DE will be calculated with the trapezoid method. Time tm is defined as the time after C\[max\] is reached where API concentration is reduced to the levels of the same day baseline.

  Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.

• AUC(0-inf), Area Under the Curve (AUC) of Albuterol or Epinephrine From Time 0 to Infinity

  Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. AUC(0-inf) will be calculated with the extrapolation method.

  Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.

Secondary Outcomes (2)

• t[Max], Time at Which Maximum Plasma Concentration of Albuterol or Epinephrine is Observed

  Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.

• t[1/2], Terminal Elimination Half-life of Albuterol or Epinephrine

  Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.

Study Arms (3)

Primatene Mist, E004

EXPERIMENTAL

Participants who dosed with Primatene Mist.

Combination Product: Epinephrine (0.125 mg/inhalation)

Epinephrine Injection Auto-Injector (Generic of EpiPen)

ACTIVE COMPARATOR

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

Combination Product: Epinephrine Injection Auto-Injector (0.3mg/0.3mL)

Albuterol HFA

ACTIVE COMPARATOR

Participants who dosed with Albuterol HFA.

Combination Product: Albuterol Sulfate (0.09 mg/inhalation)

Interventions

Epinephrine (0.125 mg/inhalation) COMBINATION_PRODUCT

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

Also known as: Primatene Mist

Primatene Mist, E004

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

Also known as: Generic of EpiPen

Epinephrine Injection Auto-Injector (Generic of EpiPen)

Albuterol Sulfate (0.09 mg/inhalation) COMBINATION_PRODUCT

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

Also known as: Albuterol HFA

Albuterol HFA

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amphastar Pharmaceuticals, Inc.: lead

Study Sites (1)

Amphastar Study Site 0035

Cypress, California, 90630, United States

Location

Related Publications (1)

• 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.

  PMID: 39207239 DERIVED

MeSH Terms

Conditions

Asthma; Anaphylaxis

Interventions

Epinephrine; Inhalation; Albuterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Amphastar Pharmaceuticals, Inc.
• Organization: Amphastar Pharmaceuticals, Inc.

info@amphastar.com

(909) 980-9484

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: December 23, 2019
• Study Start: December 9, 2019
• Primary Completion: December 20, 2019
• Study Completion: December 23, 2019
• Last Updated: March 30, 2021
• Results First Posted: March 30, 2021

Record last verified: 2021-03

Locations

US (1)