Epinephrine Inhalation Aerosol USP, a HFA-MDI Study 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 HFA-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. The current study is designed for a more thorough evaluation of the E004 Pharmacokinetics. Safety of E004 will also be evaluated, under augmented dose conditions.

Detailed Description
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E004 is formulated with epinephrine free base as the active ingredient, and hydrofluoroalkane (HFA-134a) as the propellant. In order to differentiate the inhaled epinephrine from the fluctuating background of endogenous epinephrine 1, a stable-isotope deuterium (2H) labeled epinephrine (epinephrine-d3) preparation will be used to formulate E004 inhalers, denoted as E004-d3. PK of E004 at 125 mcg of epinephrine-d3 per inhalation, will be compared to that of the currently marketed, non-labeled, Epinephrine-CFC MDI as the Reference Control (220 mcg per inhalation). This study is a randomized, evaluator-blind, single dose, two-arm, crossover, PK study, to be conducted in  18 healthy, male and female, adult volunteers. PK will be studied using E004-d3 at 125 mcg per inhalation (Arm T). A currently marketed, non-labeled, Epinephrine CFC-MDI will be used as a Reference Control (Arm C).

Official Title
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Epinephrine Inhalation Aerosol USP, an HFA-MDI CLINICAL STUDY-B2 FOR ASSESSMENT OF PHARMACOKINETICS (A Randomized, Evaluator-Blind, Single-Dose, Two Arm, Crossover, PK Study in Healthy Volunteers)

Conditions
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Asthma, Bronchospasm, Wheezing, Shortness of Breath

Intervention / Treatment
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* Drug: Epinephrine Inhalation Aerosol, HFA
* Drug: Epinephrine Inhalation Aerosol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy at screening; No clinically significant respiratory, cardiovascular and other systemic or organic illnesses; Body weight ≥ 50 kg for men and ≥ 45 kg for women, Sitting blood pressure ≤ 135/90 mm Hg; Demonstrating negative HIV, HBsAg and HCV-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; 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 studies, or donated blood, in the last 30 days; 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: Epinephrine Inhalation Aerosol, HFA<br>Experimental treatment of 10 inhalations of 125 mcg epinephrine base propelled by HFA 134a | Drug: Epinephrine Inhalation Aerosol, HFA<br>* 10 inhalations of epinephrine inhalation aerosol, 125 mcg/inhalation<br>* Other names: HFA epinephrine inhalation aerosol, 125 mcg/inhalation;|
| Active Comparator: Epinephrine Inhalation Aerosol, CFC<br>Epinephrine Inhalation Aerosol, CFC propelled, 220 mcg/inhalation , 10 inhalations | Drug: Epinephrine Inhalation Aerosol<br>* Epinephrine Inhalation Aerosol, 220 mcg/ inhalation, 10 inhalations<br>* Other names: Epinephrine Inhalation Aerosol, USP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Concentration (C0) of Total Epinephrine | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at Baseline (prior to dosing) in each treatment period following a specified washout period (3-14 days), and were analyzed using an established analysis method. Baseline concentration (C0) is the concentration of epinephrine measured in the plasma at this time point. | 0 to 30 minutes prior to dosing | 
| Peak Concentration (Cmax) of Total Epinephrine From Time Zero to 6 Hours Post-dose | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Peak (maximum) concentration (Cmax) is the highest concentration of epinephrine measured in plasma during the treatment period. | Pre-dose to 6 hours post-dose | 
| Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) for Total Epinephrine | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Area under the curve from time zero to 6 hours post-dose (AUC[0-6]) was calculated using the trapezoidal rule. | Pre-dose to 6 hours post-dose | 
| Time to Reach Peak Concentration (Tmax) for Total Epinephrine | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Tmax is the amount of time it takes for epinephrine to reach peak concentration in plasma during the treatment period. | Pre-dose to 6 hours post-dose | 
| Half-life (t1/2) of Total Epinephrine | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Half-life (t1/2) is the amount of time it takes for epinephrine to decrease to half the peak concentration in plasma during the treatment period. | Pre-dose to 6 hours post-dose | 
| Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose | Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. | Pre-dose to 6 hours post-dose | 

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