Epinephrine Inhalation Aerosol USP, CLINICAL STUDY-B3 FOR ASSESSMENT OF PHARMACOKINETICS

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT01255709

First Posted: December 7, 2010

Last Update Posted: March 17, 2016

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.

Information provided by (Responsible Party):

Amphastar Pharmaceuticals, Inc.

Purpose

This study examines the pharmacokinetic profile of Armstrong's proposed Epinephrine Inhalation Aerosol USP, an HFA134a propelled Metered Dose Inhaler (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.

Condition	Intervention	Phase
Asthma	Drug: Arm T1: Primatene Mist HFA Drug: Arm T2: Primatene Mist HFA Drug: Arm C: Primatene Mist (epinephrine inhalation aerosol, USP)	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Triple (Participant, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	CLINICAL STUDY-B3 FOR ASSESSMENT OF PHARMACOKINETICS, A Randomized, Evaluator-Blind, Single-Dose, Three Arm, Crossover,PK Study in Healthy Volunteers

Resource links provided by NLM:

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

U.S. FDA Resources

Further study details as provided by Amphastar Pharmaceuticals, Inc.:

Primary Outcome Measures:

Pharmacokinetics including maximum concentration and area under the curve [ Time Frame: -30, 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 min postdose. ]
Samples will be analyzed with an established LC/MS/MS method, with a quantitative detection limit of 0.02 ng/mL, for both epinephrine-d3 and epinephrine-h3.
- Mean Maximum concentration of epinephrine (Cmax for epinephrine)
- Mean Area Under the Curve (AUC) for epinephrine
- Time to maximum concentration (tmax) and Half life of the drug (t1/2)
- Epinephrine concentrations versus time

Secondary Outcome Measures:

Vital Signs [ Time Frame: within 30 min predose, at 30, 60 and 360 min postdose ]
Systolic and Diastolic Blood pressure and heart rate
12-lead Electrocardiogram (ECG) [ Time Frame: within 30 min pre-dose, and at 15 and 120 min post-dose ]
12 lead ECG (Routine and QT/QTc intervals)
Telemetry ECG [ Time Frame: within 30 min pre-dose, and during the initial 5 min post-dose ]
Telemetry recording of heart rate


Enrollment:	24
Study Start Date:	December 2010
Study Completion Date:	January 2011
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm T1 Primatene Mist HFA epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes	Drug: Arm T1: Primatene Mist HFA epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes Other Name: epinephrine inhalation aerosol
Active Comparator: Arm C Primatene Mist epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes	Drug: Arm C: Primatene Mist (epinephrine inhalation aerosol, USP) epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes Other Name: epinephrine inhalation aerosol
Experimental: Arm T2 Primatene Mist HFA epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes	Drug: Arm T2: Primatene Mist HFA epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes Other Name: epinephrine inhalation aerosol

Detailed Description:

The current study is designed to complement and expand the previous PK studies, API-E004-CL-B and API-E004-CL-B2, with emphasis on lower E004 dose strengths (at 90 and 100 mcg per inhalation), for a more thorough evaluation of the E004 PK profiles. Safety of E004 will also be evaluated, under augmented dose conditions.

Eligibility

Information from the National Library of Medicine

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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;
Body weight ≥ 50 kg for men and ≥ 45 kg for women;
Sitting blood pressure ≤ 135/90 mmHg;
Demonstrating negative hIV, HBsAG and DCV-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 prior to Screening;
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 drug/device studies, or donated blood, in the last 30 days prior to Screening;
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): NCT01255709

Locations


United States, California
Amphastar Study Site 1
Cypress, California, United States, 90630

Sponsors and Collaborators

Amphastar Pharmaceuticals, Inc.

Investigators


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.


Responsible Party:	Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01255709 History of Changes
Other Study ID Numbers:	API-E004-CL-B3
First Submitted:	December 3, 2010
First Posted:	December 7, 2010
Last Update Posted:	March 17, 2016
Last Verified:	February 2016

Keywords provided by Amphastar Pharmaceuticals, Inc.:


Asthma shortness of breath wheezing

Additional relevant MeSH terms:


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

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