Clinical trial 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
Official title: Study of Drug Exposure in Systemic Circulation of Primatene Mist (0.25mg) by Oral Inhalation, Versus Epinephrine Injection (0.30mg) by Intramuscular Injection and ProAir (0.18mg) by Oral Inhalation in Healthy Individuals: A Randomized, Safety Evaluator-blind, Three-Treatment, Crossover, Fasting Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pharmacokinetics
Epinephrine
Albuterol
Asthma
Anaphylaxis
Lead sponsor: Amphastar Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-12-23
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: C[Max], Maximum Plasma Concentration of Albuterol or Epinephrine
timeFrame: 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.
measure: 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)
timeFrame: 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.
measure: AUC(0-tm)_DE, Area Under the Curve (AUC) of Exogenous Active Product Ingredient (API) From Time 0 to Time (tm)
timeFrame: 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.
measure: AUC(0-inf), Area Under the Curve (AUC) of Albuterol or Epinephrine From Time 0 to Infinity
timeFrame: 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:
measure: t[Max], Time at Which Maximum Plasma Concentration of Albuterol or Epinephrine is Observed
timeFrame: 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.
measure: t[1/2], Terminal Elimination Half-life of Albuterol or Epinephrine
timeFrame: 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.
Other outcomes:
Locations:
city: Cypress
country: United States
facility: Amphastar Study Site 0035
state: California
Study officials:
References: