Study of Safety of Foradil in Patients With Persistent Asthma

A 26 Week, Randomized, Active-controlled Safety Study of Double-blind Formoterol Fumarate in Free Combination With an Inhaled Corticosteroid Versus an Inhaled Corticosteroid in Adolescent and Adult 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).