Epinephrine Inhalation Aerosol USP, CLINICAL STUDY-B3 FOR ASSESSMENT OF PHARMACOKINETICS

Study Overview
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Brief Summary
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This study examines the pharmacokinetic profile of Armstrong's proposed Epinephrine Inhalation Aerosol USP, an HFA134a propelled Metered Dose Inhaler (MDI) (E004), using a stable isotope deuterium-labeled epinephrine (epinephrine-d3) to differentiate the administered drug from the endogenous epinephrine, in healthy male and female adult volunteers.

Detailed Description
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The current study is designed to complement and expand the previous PK studies, API-E004-CL-B and API-E004-CL-B2, with emphasis on lower E004 dose strengths (at 90 and 100 mcg per inhalation), for a more thorough evaluation of the E004 PK profiles. Safety of E004 will also be evaluated, under augmented dose conditions.

Official Title
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CLINICAL STUDY-B3 FOR ASSESSMENT OF PHARMACOKINETICS, A Randomized, Evaluator-Blind, Single-Dose, Three Arm, Crossover,PK Study in Healthy Volunteers

Conditions
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Asthma

Intervention / Treatment
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* Drug: Arm T1: Primatene Mist HFA
* Drug: Arm T2: Primatene Mist HFA
* Drug: Arm C: Primatene Mist (epinephrine inhalation aerosol, USP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy at screening; Body weight ≥ 50 kg for men and ≥ 45 kg for women; Sitting blood pressure ≤ 135/90 mmHg; Demonstrating negative hIV, HBsAG and DCV-Ab screen tests; Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control; Properly consented Other criteria apply Exclusion Criteria: A smoking history of ≥10 pack-years, or having smoked within 6 months prior to Screening; Upper respiratory tract infections within 2 wk, or lower respiratory tract infection within 4 wk, prior to Screening; Any current or recent respiratory conditions that might significantly affect pharmacodynamic response to the study drugs; Known intolerance or hypersensitivity to the study MDI ingredients; Having been on other investigational drug/device studies, or donated blood, in the last 30 days prior to Screening; Other criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm T1 Primatene Mist HFA<br>epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes | Drug: Arm T1: Primatene Mist HFA<br>* epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes<br>* Other names: epinephrine inhalation aerosol;|
| Active Comparator: Arm C Primatene Mist<br>epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes | Drug: Arm C: Primatene Mist (epinephrine inhalation aerosol, USP)<br>* epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes<br>* Other names: epinephrine inhalation aerosol;|
| Experimental: Arm T2 Primatene Mist HFA<br>epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes | Drug: Arm T2: Primatene Mist HFA<br>* epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes<br>* Other names: epinephrine inhalation aerosol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics including maximum concentration and area under the curve | Samples will be analyzed with an established LC/MS/MS method, with a quantitative detection limit of 0.02 ng/mL, for both epinephrine-d3 and epinephrine-h3. Mean Maximum concentration of epinephrine (Cmax for epinephrine) Mean Area Under the Curve (AUC) for epinephrine Time to maximum concentration (tmax) and Half life of the drug (t1/2) Epinephrine concentrations versus time | -30, 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 min postdose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital Signs | Systolic and Diastolic Blood pressure and heart rate | within 30 min predose, at 30, 60 and 360 min postdose | 
| 12-lead Electrocardiogram (ECG) | 12 lead ECG (Routine and QT/QTc intervals) | within 30 min pre-dose, and at 15 and 120 min post-dose | 
| Telemetry ECG | Telemetry recording of heart rate | within 30 min pre-dose, and during the initial 5 min post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, shortness of breath, wheezing