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NCT Number: NCT01188577

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

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.

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Key information

Conditions

Asthma Bronchial Diseases Bronchial Spasm Bronchospasm Dyspnea Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Lung Diseases Lung Diseases, Obstructive Pathological Conditions, Signs and Symptoms Respiration Disorders Respiratory Hypersensitivity Respiratory Sounds Respiratory Tract Diseases Shortness of Breath Signs and Symptoms Signs and Symptoms, Respiratory Wheezing

Age range

18 year–30 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Amphastar Site 0035

Cypress, California, 90630, United States

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Epinephrine Inhalation Aerosol, HFA

Drug

10 inhalations of epinephrine inhalation aerosol, 125 mcg/inhalation

Other names: HFA epinephrine inhalation aerosol, 125 mcg/inhalation

epinephrine inhalation aerosol

Drug

Epinephrine Inhalation Aerosol, 220 mcg/ inhalation, 10 inhalations

Other names: Primatene Mist, Epinephrine Inhalation Aerosol, USP

Primary outcomes

  1. Baseline Concentration (C0) of Total Epinephrine

    Time frame: 0 to 30 minutes prior to dosing

    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.

  2. Peak Concentration (Cmax) of Total Epinephrine From Time Zero to 6 Hours Post-dose

    Time frame: Pre-dose 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.

  3. Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) for Total Epinephrine

    Time frame: Pre-dose 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. Area under the curve from time zero to 6 hours post-dose (AUC[0-6]) was calculated using the trapezoidal rule.

  4. Time to Reach Peak Concentration (Tmax) for Total Epinephrine

    Time frame: Pre-dose 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. Tmax is the amount of time it takes for epinephrine to reach peak concentration in plasma during the treatment period.

  5. Half-life (t1/2) of Total Epinephrine

    Time frame: Pre-dose 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. 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.

  6. Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose

    Time frame: Pre-dose 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.

Sponsors and collaborators

Lead sponsor

Amphastar Pharmaceuticals, Inc.

Industry

Registry information

Official study title

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)

Important dates

Study start
2010
Primary completion
2010
Study completion
2011
First posted
Aug 25, 2010
Registry last updated
Jul 25, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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