Study of Safety of Foradil in Patients With Persistent Asthma

This is a 26 week, double blind, randomized, active-controlled safety study of Foradil in
free combination with inhaled corticosteroid versus an inhaled corticosteroid alone in
adults and adolescent patients with persistent asthma. The primary objective of the study is
to demonstrate that the addition of formoterol fumarate to fluticasone propionate is
non-inferior to fluticasone propionate alone in terms of the risk of composite serious
asthma related events (asthma-related hospitalization, asthma-related intubation, and
asthma-related death). The individual components of the composite primary endpoint (i.e.,
asthma-related hospitalization, asthma-related intubation and asthma-related death) will be
assessed as a secondary safety endpoints.

The efficacy assessment is the secondary objective.

Inclusion Criteria:

1. Written informed consent, and assent if applicable, must be obtained before any
assessment is performed.

2. Male or female patients 12 years of age and older

3. Confirmed diagnosis of persistent asthma, as defined by national and international
asthma guidelines (e.g., GINA; NIH; etc.) for at least 1 year prior to study
enrollment.

4. PEF≥50% of predicted normal value.

5. Current and appropriate use of one of the treatments listed in the protocol for
asthma.

6. Recent asthma exacerbation between 30 days and 12 months prior to randomization that
either:

- required treatment with systemic corticosteroids (tablets, suspension, or
injection) or

- required hospitalization (defined as an inpatient stay or >24-hour stay in an
observation area in an emergency room or other equivalent facility)

Exclusion Criteria:

1. History of life-threatening asthma episode that required intubation and/or was
associated with hypercapnia requiring non-invasive ventilatory support.

2. Current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease,
allergic bronchopulmonary aspergillosis, cystic fibrosis, bronchopulmonary dysplasia,
or other respiratory abnormalities other than asthma.

3. Current evidence of, or past physician assessment of, chronic bronchitis, emphysema,
or chronic obstructive pulmonary disease.

4. History of smoking ≥ 10 pack years.

5. Exercise induced asthma (as the only asthma-related diagnosis) not requiring daily
asthma control medicine.

6. Suspected or documented bacterial or viral infection of the upper or lower
respiratory tract, sinus or middle ear that is not resolved at randomization.

7. Worsening/Unstable asthma within 7 days prior to randomization.

8. Any asthma exacerbation requiring systemic corticosteroids within 30 days of
randomization or more than 4 separate exacerbations in the 12 months preceding
randomization.

9. Two or more hospitalizations for greater than 24 hours duration for treatment of
asthma in the 12 months preceding randomization.

10. History of hypersensitivity to any beta2-agonist, sympathomimetic drug, inhaled
corticosteroids, or systemic corticosteroid therapy or any component of the possible
study treatments in this trial, including severe milk protein hypersensitivity.

11. Use of anti-IgE (e.g., omalizumab) or any other monoclonal antibody, in the 6 months
prior to randomization.

12. Use of (Beta) β-blockers within 1 day prior to first dose of study medication.

13. Use of ICS, LABA, ICS+LABA, LTRAs, leukotriene modifiers, anticholinergics, or
theophylline must be discontinued prior to the first dose of investigational
treatment.

14. Use of a potent CYP3A4 inhibitor within 4 weeks of randomization (e.g., ritonavir,
atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir,
saquinavir, ketoconazole, telithromycin).