NCT04207840

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

Completed Phase 4 Results posted Last updated 30 March 2021

What this trial tests

Phase 4 trial testing Epinephrine (0.125 mg/inhalation) in Pharmacokinetics in 28 participants. Completed in 23 December 2019.

Timeline

9 December 2019

Primary endpoint
20 December 2019

23 December 2019

Quick facts

Lead sponsor	Amphastar Pharmaceuticals, Inc.
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	single
Primary purpose	treatment
Enrollment	28
Start date	9 December 2019
Primary completion	20 December 2019
Estimated completion	23 December 2019
Sites	1 location across United States

Drugs / interventions tested

• Epinephrine (0.125 mg/inhalation)
• Epinephrine Injection Auto-Injector (0.3mg/0.3mL)
• Albuterol Sulfate (0.09 mg/inhalation)

Conditions studied

• Pharmacokinetics — all drugs for Pharmacokinetics →
• Epinephrine — all drugs for Epinephrine →
• Albuterol — all drugs for Albuterol →
• Asthma — all drugs for Asthma →

Sponsor

Amphastar Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 18 to 50, any sex, with Pharmacokinetics or Epinephrine. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

C[Max], Maximum Plasma Concentration of Albuterol or Epinephrine Primary · 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.

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.

Group	Value	95% CI
Primatene Mist, E004	240.8	± 2.4
Epinephrine Injection Auto-Injector (Generic of EpiPen)	704.8	± 1.8
Albuterol HFA	599.8	± 1.7

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) Primary · 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.

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.

Group	Value	95% CI
Primatene Mist, E004	26.8	± 3.1
Epinephrine Injection Auto-Injector (Generic of EpiPen)	509.9	± 1.5
Albuterol HFA	3332.3	± 1.3

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

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.

Group	Value	95% CI
Primatene Mist, E004	18.4	± 3.6
Epinephrine Injection Auto-Injector (Generic of EpiPen)	396.3	± 1.6
Albuterol HFA	3332.3	± 1.3

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

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.

Group	Value	95% CI
Primatene Mist, E004	18.4	± 3.6
Epinephrine Injection Auto-Injector (Generic of EpiPen)	411.4	± 1.7
Albuterol HFA	3650.4	± 1.3

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

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. t\[max\] will be obtained directly from the plot of PK curve when the maximum concentration is observed.

Group	Value	95% CI
Primatene Mist, E004	2.6	± 3.0
Epinephrine Injection Auto-Injector (Generic of EpiPen)	8.3	± 2.7
Albuterol HFA	21.8	± 3.1

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

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.

Group	Value	95% CI
Primatene Mist, E004	7.1	± 5.2
Epinephrine Injection Auto-Injector (Generic of EpiPen)	138.8	± 4.0
Albuterol HFA	420.7	± 1.2

Adverse events — posted to ClinicalTrials.gov

Time frame: From signing of consent until follow-up (approximately 4 weeks). Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Primatene Mist, E004

Serious: 0/27 (0%)

Deaths: 0/27

Epinephrine Injection Auto-Injector (Generic of EpiPen)

Serious: 0/26 (0%)

Deaths: 0/26

Albuterol HFA

Serious: 0/28 (0%)

Deaths: 0/28

Other adverse events (4 terms — click to expand)

Reaction	System	Primatene Mist, E004	Epinephrine Injection Auto…	Albuterol HFA
Headache	Nervous system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Injection Site Pain	General disorders	—	—	—
Nasopharyngitis	Respiratory, thoracic and mediastinal disorders	—	—	—

Data from ClinicalTrials.gov NCT04207840 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Comparison of Systemic Exposure Between Epinephrine Delivered via Metered-Dose Inhalation and Intramuscular Injection.
   Zhang JY, Luo MZ, Marrs T, Kerwin EM, et al · · 2025 · PMID 39207239 · DOI 10.1089/jamp.2024.0025