Randomized, Placebo-controlled, Multi-dose, Study Comparing Budesonide/Formoterol to Symbicort® in Asthmatic Patients

This is a pivotal trial that will examine therapeutic equivalence of a new generic fixed-dose
combination product containing Budesonide 80 mcg / Formoterol fumarate dihydrate 4.5 mcg and
reference listed drug (RLD) Symbicort® inhalation aerosol in adult patients with chronic but
stable asthma as defined in National Asthma Education and Prevention Program Expert Panel
Report 3 (NAEPP 3) guidelines. To ensure adequate study sensitivity the test and reference
products should both be statistically superior to placebo (p<0.05) with regard to the
bioequivalent study primary endpoints.

A secondary study objective is the safety and tolerability of the test compound.

Inclusion Criteria:

- Adult male or female subjects of non-childbearing or of childbearing potential
committed to consistent and correct use of an acceptable method of birth control

- Diagnosed with asthma, as defined by the National Asthma Education and Prevention
Program (NAEPP),at least 6 months prior to screening

- Moderate-to-severe asthma with a pre-bronchodilator FEV1 of >45% and <85% of predicted
normal, measured at least 6 hours after short-acting β agonist (SABA)and at least 24
hours after the last dose of long-acting β agonist (LABA), at the screening visit and
on the day of treatment

- >15% and >0.20 L reversibility of FEV1 within 30 minutes following 360 mcg of
albuterol inhalation (pMDI)

- Patients should be stable on their chronic asthma treatment regimen for at least 4
weeks prior to enrollment

- Currently non-smoking; having not used tobacco products (i.e., cigarettes, cigars,
pipe tobacco) within the past year, and having < 10 pack-years of historical use

- Able to replace current regularly scheduled short-acting β agonists (SABAs) with
salbutamol/albuterol inhaler for use only on an as-needed basis for the duration of
the study (subjects should be able to withhold all inhaled SABAs for at least 6 hours
prior to lung function assessments on study visits)

- Willing to discontinue their asthma medications (inhaled corticosteroids and
long-acting β agonists) during the run-in period and for the remainder of the study

- Willingness to give their written informed consent to participate in the study

Exclusion Criteria:

- Life-threatening asthma, defined as a history of asthma episodes(s) requiring
intubation, and/or associated with hypercapnia, respiratory arrest or hypoxic
seizures, asthma-related syncopal episodes(s), or hospitalizations within the past
year or during the run-in period

- Significant respiratory disease other than asthma (chronic obstructive pulmonary
disease (COPD), interstitial lung disease, etc.)

- Evidence or history of clinically significant disease or abnormality including
congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery
disease, myocardial infarction, or cardiac dysrhythmia. In addition, historical or
current evidence of significant hematologic, hepatic, neurologic, psychiatric, renal,
or other diseases that, in the opinion of the investigator, would put the patient at
risk through study participation, or would affect the study analyses if the disease
exacerbated during the study

- Patients who required systemic corticosteroids (for any reason) within the past 4
weeks

- Hypersensitivity to any sympathomimetic drug (e.g., formoterol or albuterol) or any
inhaled, intranasal, or systemic corticosteroid therapy

- Patients currently receiving β-blockers