Evaluation of Efficacy and Safety of E004 in Children With Asthma

Study Overview
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Brief Summary
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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.

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

Conditions
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Asthma

Intervention / Treatment
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* Drug: E004 (Epinephrine Inhalation Aerosol) HFA-MDI
* Drug: Placebo-HFA


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild bronchial asthma