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

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: Treatment arm T1 Drug: Treatment arm T2 Drug: Treatment arm C	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, 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:

MedlinePlus related topics: Asthma

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. ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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: Treatment arm T1 epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes	Drug: Treatment arm T1 epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes Other Name: Primatene Mist HFA
Active Comparator: Treatment arm C epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes	Drug: Treatment arm C epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes Other Name: Primatene Mist (epinephrine inhalation aerosol, USP)
Experimental: Treatment arm T2 epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes	Drug: Treatment arm T2 epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes Other Name: Primatene Mist HFA

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

Ages Eligible for Study:	18 Years to 30 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: 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:	Medical Director, Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01255709 History of Changes
Other Study ID Numbers:	API-E004-CL-B3
Study First Received:	December 3, 2010
Last Updated:	January 27, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Amphastar Pharmaceuticals, Inc.:

Asthma
shortness of breath
wheezing

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Epinephrine
Epinephryl borate
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Mydriatics
Adrenergic alpha-Agonists
Sympathomimetics
Vasoconstrictor Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 19, 2013