Epinephrine Inhalation Aerosol USP, a HFA-MDI Study for Assessment of Pharmacokinetics

Amphastar Pharmaceuticals, Inc.23 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Asthma

Eligibility

Sex: ALLMin age: 18 YearsMax age: 30 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.