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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

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.

Study Description

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 Design

Layout table for study information

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

Resource links provided by the National Library of Medicine

Drug Information available for: Epinephrine bitartrate Epinephrine Epinephrine hydrochloride Racepinephrine hydrochloride Racepinephrine

U.S. FDA Resources

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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.
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.
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.
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.
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.
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.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

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

Contacts and Locations

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

Layout table for location information

United States, California
Amphastar Site 0035
Cypress, California, United States, 90630

Sponsors and Collaborators

Amphastar Pharmaceuticals, Inc.

Investigators

Layout table for investigator information

Study Director:	Medical Director	Amphastar Pharmaceuticals, Inc.

More Information

Publications:

Pinnas JL, Schachtel BP, Chen TM, Roseberry HR, Thoden WR. Inhaled epinephrine and oral theophylline-ephedrine in the treatment of asthma. J Clin Pharmacol. 1991 Mar;31(3):243-7.

Hendeles L, Marshik PL, Ahrens R, Kifle Y, Shuster J. Response to nonprescription epinephrine inhaler during nocturnal asthma. Ann Allergy Asthma Immunol. 2005 Dec;95(6):530-4.

Warren JB, Doble N, Dalton N, Ewan PW. Systemic absorption of inhaled epinephrine. Clin Pharmacol Ther. 1986 Dec;40(6):673-8.

Cripps A, Riebe M, Schulze M, Woodhouse R. Pharmaceutical transition to non-CFC pressurized metered dose inhalers. Respir Med. 2000 Jun;94 Suppl B:S3-9.

Dickinson BD, Altman RD, Deitchman SD, Champion HC. Safety of over-the-counter inhalers for asthma: report of the council on scientific affairs. Chest. 2000 Aug;118(2):522-6.

Simons FE, Gu X, Johnston LM, Simons KJ. Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis? Pediatrics. 2000 Nov;106(5):1040-4.

Kushner DJ, Baker A, Dunstall TG. Pharmacological uses and perspectives of heavy water and deuterated compounds. Can J Physiol Pharmacol. 1999 Feb;77(2):79-88. Review.

Bondesson E, Friberg K, Soliman S, Löfdahl CG. Safety and efficacy of a high cumulative dose of salbutamol inhaled via Turbuhaler or via a pressurized metered-dose inhaler in patients with asthma. Respir Med. 1998 Feb;92(2):325-30.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kerwin EM, Marrs T, Luo MZ, Zhang JY. Pharmacokinetic Study of Epinephrine Hydrofluoroalkane (Primatene MIST) Metered-Dose Inhaler. J Aerosol Med Pulm Drug Deliv. 2020 Oct;33(5):282-287. doi: 10.1089/jamp.2019.1577. Epub 2020 May 18.

Layout table for additonal information

Responsible Party:	Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01188577
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:

Layout table for MeSH terms

Bronchial Spasm Dyspnea Respiratory Sounds Bronchial Diseases Respiratory Tract Diseases Respiration Disorders Signs and Symptoms, Respiratory Epinephrine Racepinephrine Epinephryl borate 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

To Top