Safety Study in Adolescent and Adult Patients With Asthma

A 3-month Safety Evaluation Extension to the 12-week E004-C Study in Asthma Patients (A Double Blinded, Placebo-controlled, Parallel, 3-month Safety Study in Adolescent and Adult Patients With Asthma)

E004-C2 is a continuation of E004-C for safety evaluations with additional 3 months to be able to assess the 6-month safety profile for E004 (epinephrine inhalation) versus placebo in a double-blinded manner.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Epinephrine inhalation; Drug: Placebo; Drug: Primatene Mist

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Costa Mesa, California, United States, 92626
      • Amphastar Site 0006
    • Los Angeles, California, United States, 90048
      • Amphastar Site 0005
    • Orange, California, United States, 92868
      • Amphastar Site 0004
    • San Jose, California, United States, 95117
      • Amphastar Site 0001
    • Stockton, California, United States, 95207
      • Amphastar Site 0003
  • Colorado
    • Denver, Colorado, United States, 80230
      • Amphastar Site 0008
    • Wheat Ridge, Colorado, United States, 80033
      • Amphastar Site 0009
  • Iowa
    • Iowa City, Iowa, United States, 52240
      • Amphastar Site 0011
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Amphastar Site 0013
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Amphastar Site 0014
    • Plymouth, Minnesota, United States, 55441
      • Amphastar Site 0015
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • Amphastar Site 0016
  • Montana
    • Bozeman, Montana, United States, 59718
      • Amphastar Site 0017
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Amphastar Site 0019
  • New Jersey
    • Skillman, New Jersey, United States, 08558
      • Amphastar Site 0020
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Amphastar Site 0018
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Amphastar Site 0021
  • Oregon
    • Ashland, Oregon, United States, 97520
      • Amphastar Site 0024
    • Eugene, Oregon, United States, 97401
      • Amphastar Site 0022
    • Lake Oswego, Oregon, United States, 97035
      • Amphastar Site 0023
    • Medford, Oregon, United States, 97504
      • Amphastar Site 0025
    • Portland, Oregon, United States, 97202
      • Amphastar Site 0026
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Amphastar Site 0029
  • Texas
    • El Paso, Texas, United States, 79903
      • Amphastar Site 0031
    • New Braunfels, Texas, United States, 78130
      • Amphastar Site 0030
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Amphastar Site 0033
  • Washington
    • Seattle, Washington, United States, 98105
      • Amphastar Site 0034

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Only subjects who have successfully completed the E004-C study within the last 135 days or those who are actively enrolled in the current study E004-C at the time of the study extension initiation
• Male and female asthma patients aged 12 - 75 years
• Patients with documented asthma, requiring inhaled epinephrine or beta 2-agonist treatment
• No significant changes in asthma therapy and no asthma-related hospitalization or emergency visits, within 4 weeks prior to Screening
• Demonstrating satisfactory techniques in the use of metered-dose inhaler and a hand held peak expiratory flow meter
• Female patients of child-bearing potential must be non-pregnant and non-lactating at Screening and throughout the study, and must use an acceptable method of contraception during the study

Exclusion Criteria:

• A smoking history of 10-pack years, or having smoked within 12 months of screening
• Any current or past medical conditions that, per investigator discretion, might significantly affect responses to the study drugs, other than asthma
• Concurrent clinically significant diseases
• Known intolerance or hypersensitivity to any component of the study drugs
• Recent infection of the respiratory tract, before screening
• Use of prohibited medications
• Having been on other investigational drug/device studies in the last 30 days prior to screening
• Known or highly suspected substance abuse

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm T; Arm T is the experimental treatment arm consisting of 2 x 125 mcg/inhalations of epinephrine inhalation, QID, with 4-6 hr intervals	Drug: Epinephrine inhalation; 125 mcg/inhalation, 2 inhalations QID
Placebo Comparator: Arm P; Arm P is a placebo comparator consisting of 2× 0 mcg of placebo inhalations, QID, with 4-6 hr intervals	Drug: Placebo; 0 mcg/inhalation, 2 inhalations QID
Active Comparator: Arm A; Arm A is an active comparator, Primatene Mist, consisting of 2× 220 mcg/inhalation, QID, with 4-6 hr intervals	Drug: Primatene Mist; 220 mcg/inhalation, 2 inhalations QID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Recording of all adverse events experienced during the course of the study	up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 12 lead ECG including QT/QTc analysis	A 12-lead ECG (routine and QT/QTc) will be measured and recorded, provided that dosing of study drug has been performed greater than 1 hour prior to conducting the measurements.	Study visit 4, 8 and 12, greater than one hour after last dose
Asthma Exacerbations	Review use of resuce inhaler for treatment of asthma exacrbations occuring between doses of study medication.	up to 12 weeks

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.
• Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87. doi: 10.1164/ajrccm.159.1.9712108.
• Kerwin EM, Tashkin DP, Korenblat PE, Greos LS, Pearlman DS, Bensch GW, Miller SD, Marrs T, Luo MZ, Zhang JY. Long-term safety and efficacy studies of epinephrine HFA metered-dose inhaler (Primatene(®) Mist): a two-stage randomized controlled trial. J Asthma. 2021 May;58(5):633-644. doi: 10.1080/02770903.2020.1713147. Epub 2020 Jan 20.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: November 15, 2011
• First Submitted That Met QC Criteria: November 18, 2011
• First Posted (Estimate): November 22, 2011

Study Record Updates

• Last Update Posted (Actual): February 13, 2017
• Last Update Submitted That Met QC Criteria: February 10, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Asthma; Shortness of breath; Bronchial Asthma
• 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-C2