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

CLINICAL STUDY-B3 FOR ASSESSMENT OF PHARMACOKINETICS, A Randomized, Evaluator-Blind, Single-Dose, Three Arm, Crossover,PK Study in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Arm T1: Primatene Mist HFA; Drug: Arm C: Primatene Mist (epinephrine inhalation aerosol, USP); Drug: Arm T2: 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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: 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 Names: epinephrine inhalation aerosol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics including maximum concentration and area under the curve	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	-30, 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 min postdose.

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Amphastar Pharmaceuticals, Inc.

Publications and helpful links

General 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. doi: 10.1002/j.1552-4604.1991.tb04969.x.
• 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. doi: 10.1016/S1081-1206(10)61014-9.
• Warren JB, Doble N, Dalton N, Ewan PW. Systemic absorption of inhaled epinephrine. Clin Pharmacol Ther. 1986 Dec;40(6):673-8. doi: 10.1038/clpt.1986.243.
• 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. doi: 10.1378/chest.118.2.522.
• 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. doi: 10.1542/peds.106.5.1040.
• 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.
• Bondesson E, Friberg K, Soliman S, Lofdahl 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. doi: 10.1016/s0954-6111(98)90116-0.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 6, 2010
• First Posted (Estimate): December 7, 2010

Study Record Updates

• Last Update Posted (Estimate): March 17, 2016
• Last Update Submitted That Met QC Criteria: February 18, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Asthma; wheezing; shortness of breath
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Epinephrine; Racepinephrine; Epinephryl borate
• Other Study ID Numbers: API-E004-CL-B3