Study of Safety of Foradil in Patients With Persistent Asthma
Study of Safety of Foradil in Patients With Persistent Asthma
The purpose of this study was to assess whether the risk of serious asthma-related events
 (asthma-related hospitalizations, asthma related intubations, and asthma related deaths) in
 adolescents and adults (12 years of age and older) taking inhaled formoterol
 fumarate/fluticasone propionate combination was the same as those taking inhaled fluticasone
 propionate alone.
This was 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 was 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.
Key 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)

 Key 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).