Evaluation of Efficacy and Safety of E004 in Children With Asthma

Phase III Study of Epinephrine Inhalation Aerosol for Evaluation of Efficacy and Safety of E004 in Children With Asthma

This is a multi-center, randomized, double-blinded, placebo-controlled, parallel, 4-week study in 60 pediatric patients (4-11 years old) with asthma, comparing E004 with Placebo HFA-MDI in pediatric patients who are 4-11 years of age with asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo-HFA; Drug: E004 (Epinephrine Inhalation Aerosol) HFA-MDI

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Costa Mesa, California, United States, 92626
      • Amphastar Site 5
    • Orange, California, United States, 92868
      • Amphastar Site 8
    • Stockton, California, United States, 95207
      • Amphastar Site 4
  • Oregon
    • Medford, Oregon, United States, 97504
      • Amphastar Site 2
    • Portland, Oregon, United States, 97202
      • Amphastar Site 1
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Amphastar Site 7
  • Texas
    • El Paso, Texas, United States, 79903
      • Amphastar Site 3
    • San Antonio, Texas, United States, 78229
      • Amphastar Site 6

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Generally healthy male, and premenarchal female, children aged 4 - 11 years upon Screening.
• With documented asthma, requiring inhaled epinephrine or beta2-agonist treatment, with or without concurrent anti-inflammatory therapies for at least 6-months prior to Screening.
• Being capable of performing spirometry for FEV1
• Satisfying criteria of asthma
• Can tolerate withholding treatment with inhaled bronchodilators and other allowed medications for the minimum washout periods
• Demonstrating a Screening Baseline FEV1 that is 50 - 90% of Polgar predicted normal value.
• Demonstrating an Airway Reversibility,
• Demonstrating satisfactory techniques in the use of a metered-dose inhaler (MDIs) and a hand held peak expiratory flow meter, after training.
• Has been properly consented to participate in this study.

Exclusion Criteria:

• Any current or past medical conditions that, per investigator discretion, might significantly affect pharmacodynamic responses to the study drugs
• Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, or malignant diseases.
• Known intolerance or hypersensitivity to any component of the study drugs
• Recent infection of the respiratory tract
• Use of prohibited medications
• Having been on other investigational drug/device studies in the last 30 days prior to screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: P - Placebo-HFA; Placebo-HFA, 0 mcg/inhalation, 2 inhalations QID	Drug: Placebo-HFA; Placebo-HFA, 0 mcg/inhalation, 2 inhalations QID
Experimental: T - E004 (Epinephrine Inhalation Aerosol) HFA-MDI; E004 (Epinephrine Inhalation Aerosol) HFA-MDI, 125 mcg/inhalation, 2 inhalations QID	Drug: E004 (Epinephrine Inhalation Aerosol) HFA-MDI; E004 (Epinephrine Inhalation Aerosol) HFA-MDI, 125 mcg/inhalation, 2 inhalations QID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy Endpoint AUC of FEV1's relative change	bronchodilator effect expressed as AUC of FEV1's relative change (from the same day baseline) versus time, defined as AUC of ΔFEV1%.	Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of FEV1 volume changes (AUC of change in FEV1)	determination of the change in FEV1 from baseline at visit to to post treatment at Visit 3	Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Maximum of change in FEV1% (Fmax)	Evaluation of maximum percent change in FEV1	Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Curves of change in FEV1, and change in FEV1%, versus time	Evaluation of curves of change in FEV1 and percent change in FEV1 over time	Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Time to onset of bronchodilator effect (to onset), determined the time point (within 60 minutes) where FEV1 first reaches ≥12% above Same-Day Baseline.	Evaluation of how much time elapses (within 60 minutes), until FEV1 first reaches ≥12% above Same-Day Baseline.	Study Visits 1and 3 within 60 minutes post dose
The time to peak FEV1 effect (tmax), defined as the time of Fmax.	Evaluation of how much time elapses until FEV1 reaches its peak	Study Visits 1 and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Duration of efficacy (duration), defined as the total length of time when ΔFEV1% reaches and stays ≥12% above Same-Day Baseline.	Evaluation of the total length of time it takes until the change in FEV1% reaches and stays ≥12% above Same-Day Baseline.	Study Weeks 1and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Percentage of positive responders (R%), including all subjects whose Fmax reaches ≥12% above Same-Day Baseline.	Evaluation of what percentage of subjects are positive responders (R%), including all subjects whose Fmaxreaches ≥12% above Same-Day Baseline.	Study Weeks 1 and 3 within 60 minutes post dose
Mean daily morning pre-dose Peak Expiratory Flow Rate (PEF)	Evaluation of the mean of daily morning pre-dose Expiratory Flow Rate	daily pre-dose
Evaluation of Vital Signs	Monitoring of vital signs (SBP/DBP, and heart rate) at the Screening Visit (Baseline and 30 min post-dose), and at the baseline, 3, 20, 60 and 360 minute time points during the study	predose, and 3, 20, 60, 360 minutes post-dose
12-lead ECG	Recording of 12-lead ECG (Routine and QT/QTc) at Screening Visit Baseline, and at the baseline, 3, 20 and 60 minute time points during Study Visits 1 and 3	Pre-dose and , 3, 20 and 60 minutes post-dose (Study Visits 1 and 3)
Albuterol HFA usage for rescue relief of acute asthma symptoms	Evaluation Albuterol HFA usage for rescue relief of acute asthma symptoms	Study Visits 1, 2, and 3, within 30 min predose

Collaborators and Investigators

• Sponsor: Amphastar Pharmaceuticals, Inc.
• Investigators: Study Chair: John Gao, M.D., 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: October 24, 2011
• First Submitted That Met QC Criteria: October 25, 2011
• First Posted (Estimate): October 27, 2011

Study Record Updates

• Last Update Posted (Actual): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 27, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Mild 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
• Other Study ID Numbers: API-E004-CL-D