Evaluation of Efficacy and Safety for Single Dose of E004 in Children With Asthma

This is a randomized, double-blinded, placebo-controlled, crossover, single dose study to be
conducted in pediatric patients (4 - 11 years) with asthma.

The main features of the study design are:

The entire study consists of a Screening Visit, and a Study Period consisting of two (2)
crossover Study Visits separated by a 2 to 14-day interval. All study subjects must be
properly consented, under adult supervision, and screened against the inclusion and
exclusion criteria at the Screening Visit and confirmed for enrollment on Visit 1. Efficacy
and safety evaluations of E004 are conducted at each Study Visit.

This study employs two (2) double-blinded treatment arms as outlined in Table 2. A
double-blinded design will be applied to E004 (Arm T) and Placebo-HFA (Arm P) since they are
identical in all physical attributes and share a comparable formulation.

The enrolled subjects will be randomized into two sequences (as follows) to participate in
two (2) crossover Study Visits with a 2 - 14 day interval between visits. Randomization is
achieved using a ratio of 1:1.

Use E004 (T) and Placebo (P) in Visits 1 and 2, respectively or use Placebo (P) and E004 (T)
in Visits 1 and 2, respectively

Subjects will be trained at the screening visit and each Study Visit for the correct dosing
and spirometry methods. Under the supervision of dosing monitor, subjects will
self-administer two (2) inhalations of the randomized study treatment, with a ~1 min
interval at each Study Visit.

For the Screening and Study Visits, the subjects will be required to be at the site for a 30
minute "resting period". This resting period is designed to maintain a stable and consistent
physical status of the subjects prior to the start of the baseline FEV1 procedures. For the
Screening Visit, this period will begin upon subject arrival. For the Study Visits, the
period will begin at the end of the option breakfast (or upon arrival if the breakfast is
declined).

For each Study Visit, subjects will need to arrive at the study site early enough to
complete all necessary baseline evaluations. The study site will provide an optional
breakfast but it must be eaten at least 30 minutes prior to the pre-dose baseline FEV1
measurements. The optional breakfast will be light, and contain no added sugar. If the
subjects decline the breakfast (i.e. they have already eaten a light breakfast prior to
arriving), they are required to remain at the site for at least 30 minutes prior to the
start of the Baseline FEV1 measurements, in order to maintain a stable physical status.

Baseline vital signs and safety evaluations will be taken prior to the pre-dose baseline
FEV1 measurement. These can be performed during the 30 minute "resting period". Efficacy of
the treatments at each visit will be evaluated based on spirometric measurements of serial
FEV1 determined at the Pre-dose Baseline, and the seven (7) serial Post-dose FEV1 responses
at 5, 30, 60, 120, 150, 180) and 240 minutes.

This study will be conducted with a double-blinded technique. This means neither the subject
nor the site staff will be aware of the identity of the treatment arm since both study
treatments are in identical looking containers.

Inclusion Criteria:

- Generally healthy male, and premenarchal female, children ages 4 - 11 years upon
Screening.

- With documented asthma, requiring inhaled epinephrine or β2-agonist treatment, with
or without concurrent anti-inflammatory therapies including orally inhaled
corticosteroids, for at least 6-months prior to Screening.

- Being capable of performing spirometry for FEV1 measurements.

- Satisfying criteria of asthma stability, defined as no significant changes in asthma
therapy (with the exception of switching LABA to SABA, adjustment of ICor SABA, etc,
per investigator discretion) and no asthma-related hospitalization or emergency room
visits, within 4 weeks prior to Screening.

- Can tolerate withholding treatment with inhaled bronchodilators and other allowed
medications for the minimum washout periods indicated in Appendix II prior to the
Screening Baseline FEV1 testing.

- Demonstrating a Mean Screening Baseline FEV1 (MSBF) that is 50.0% - 90% of Polgar
predicted normal value.

- Demonstrating an Airway Reversibility, i.e., FEV1 values ≥12% increase based upon
volume compared with MSBF, within 30 min after 2 inhalations (440 mcg, epinephrine
base) of previously marketed Epinephrine CFC-MDI, labeled "For Investigational Use
Only". There will be up to 5 reversibility time points, each with up to 5 maneuvers
that can be conducted anytime within 30 min post-dose.

- Demonstrating satisfactory techniques in the use of a metered-dose inhaler (MDI).

- 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, such as
significant systemic or respiratory diseases (e.g., cystic fibrosis, bronchiectasis,
active tuberculosis, emphysema, nonreversible pulmonary diseases), other than asthma.

- Concurrent clinically significant cardiovascular, hematological, renal, neurologic,
hepatic, endocrine, psychiatric, or malignant diseases.

- Known intolerance or hypersensitivity to any component of the study drugs (i.e.,
Epinephrine, HFA-134a, CFC-12, CFC-114, polysorbate-80, thymol, ethanol, ascorbic
acid, nitric acid, and hydrochloric acid), as well as the rescue Albuterol HFA
inhalers (i.e., Albuterol, HFA-134a, ethanol, and oleic acid).

- Recent infection of the upper respiratory tract (within 2 weeks), or lower
respiratory tract (within 4 weeks), before screening.

- Use of prohibited medications per Appendix II.

- Having been on other investigational drug/device studies in the last 30 days prior to
screening.