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

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ClinicalTrials.gov Identifier: NCT01188577
Recruitment Status : Completed
First Posted : August 25, 2010
Results First Posted : October 24, 2014
Last Update Posted : July 25, 2017
Sponsor:
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Asthma Bronchospasm Wheezing Shortness of Breath Drug: Epinephrine Inhalation Aerosol, HFA Drug: Epinephrine Inhalation Aerosol Phase 1 Phase 2

Detailed Description:

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  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official 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)
Study Start Date : August 2010
Actual Primary Completion Date : September 2010
Actual Study Completion Date : January 2011


Arm Intervention/treatment
Experimental: Epinephrine Inhalation Aerosol, HFA
Experimental treatment of 10 inhalations of 125 mcg epinephrine base propelled by HFA 134a
Drug: Epinephrine Inhalation Aerosol, HFA
10 inhalations of epinephrine inhalation aerosol, 125 mcg/inhalation
Other Name: HFA epinephrine inhalation aerosol, 125 mcg/inhalation

Active Comparator: Epinephrine Inhalation Aerosol, CFC
Epinephrine Inhalation Aerosol, CFC propelled, 220 mcg/inhalation , 10 inhalations
Drug: Epinephrine Inhalation Aerosol
Epinephrine Inhalation Aerosol, 220 mcg/ inhalation, 10 inhalations
Other Names:
  • Primatene Mist
  • Epinephrine Inhalation Aerosol, USP




Primary Outcome Measures :
  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.



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Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01188577


Locations
United States, California
Amphastar Site 0035
Cypress, California, United States, 90630
Sponsors and Collaborators
Amphastar Pharmaceuticals, Inc.
Investigators
Study Director: Medical Director Amphastar Pharmaceuticals, Inc.

Publications:
Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01188577     History of Changes
Other Study ID Numbers: API-E004-CL-B2
First Posted: August 25, 2010    Key Record Dates
Results First Posted: October 24, 2014
Last Update Posted: July 25, 2017
Last Verified: June 2017

Keywords provided by Amphastar Pharmaceuticals, Inc.:
asthma
bronchospasm
wheezing
shortness of breath

Additional relevant MeSH terms:
Epinephrine
Racepinephrine
Epinephryl borate
Respiratory Sounds
Bronchial Spasm
Dyspnea
Signs and Symptoms, Respiratory
Signs and Symptoms
Bronchial Diseases
Respiratory Tract Diseases
Respiration Disorders
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Mydriatics
Sympathomimetics
Vasoconstrictor Agents