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
Condition: Pharmacokinetics; Epinephrine; Albuterol; Asthma; Anaphylaxis
MeSH terms: Respiratory Aspiration; Anaphylaxis
Intervention: Epinephrine (0.125 mg/inhalation); Epinephrine Injection Auto-Injector (0.3mg/0.3mL); Albuterol Sulfate (0.09 mg/inhalation)
Intervention description: Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.; 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.; Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.
Intervention MeSH terms: Epinephrine; Racepinephrine; Albuterol; Epinephryl borate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Investigator)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

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.