FACTO Study (Foster® As Complete Treatment Option)

A PHASE 4, MULTINATIONAL, MULTICENTRE, DOUBLE BLIND, DOUBLE DUMMY, RANDOMIZED, PARALLEL GROUP, CONTROLLED CLINICAL STUDY OF FIXED COMBINATION BECLOMETHASONE DIPROPIONATE 100 µg PLUS FORMOTEROL FUMARATE 6 µg pMDI WITH HFA-134A PROPELLANT (CHF1535, FOSTER®) VERSUS FLUTICASONE 250 µg PLUS SALMETEROL 50 µg DPI (SERETIDE® DISKUS®) AS MAINTENANCE TREATMENT IN CONTROLLED ASTHMATIC PATIENTS.

Double blind, multinational, multicentre, randomised, 2 arm parallel group study

Aim of the present investigation is to demonstrate the clinical equivalence between fluticasone plus salmeterol 500/100 µg daily and an equipotent dose of CHF1535 in maintaining the same asthma control in patients adequately controlled with fluticasone plus salmeterol at the above mentioned daily dose.

Inclusion Criteria:

Asthmatic patients will be enrolled at Visit 1 into the run-in period if they meet all of the following criteria:

1. Written informed consent obtained

2. Adult male and female (≥18 and ≤65 years)

3. Clinical diagnosis of controlled asthma according to Global Strategy for Asthma Management and Prevention (GINA) revised version 2007 in the previous week before study entry:

   • no daytime symptoms (twice or less/week)
   • no limitations of activities
   • no nocturnal symptoms/awakenings
   • no need for reliever/rescue medications (twice or less/week)
   • lung function (FEV1) > 80% predicted or personal best (if known)

4. Patients treated with fluticasone 500 µg + salmeterol 100 µg daily for ≥ 4 weeks

5. A co-operative attitude and ability to correctly use the device and to complete the diary cards.

Exclusion Criteria:

Patients will not be enrolled at visit 1 into the run-in period if they meet any of the following criteria:

1. Inability to carry out pulmonary function testing;
2. Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) as defined by the National Heart Lung and Blood Institute/World Health Organisation (NHLBI/WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines;
3. History of near fatal asthma;
4. Evidence of severe asthma exacerbation or symptomatic infection of the lower airways in the previous six months;
5. Three or more courses of oral corticosteroids or hospitalisation due to asthma during the previous 6 months;
6. Patients treated with long-acting β2-agonists (LABAs) other than salmeterol, anticholinergics, and leukotriene antagonists during the previous 4 weeks;
7. Current smokers or recent (less than one year) ex-smokers defined as smoking at least 15 packs/year;
8. Clinically significant or unstable concurrent disease : e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; significant other pulmonary disease; cardiovascular disease; gastrointestinal disease; neurological disease; haematological disease, autoimmune disorders, that may interfere with patient's safety, compliance, or study evaluations, according to the investigator's opinion;
9. Patients with a serum potassium value ≤ 3.5 mEq/L
10. Patients with QTc interval (Bazett's formula) higher than 450 msec at screening visit 1;
11. Cancer or any chronic diseases with prognosis < 2 years;
12. Female subjects: pregnant or with active desire to be pregnant, lactating mother or lack of efficient contraception in a subject with child-bearing potential (i.e. contraceptive methods other than oral contraceptives, IUD, tubal ligature). A pregnancy test in urine is to be carried out in women of a fertile age at screening
13. Significant alcohol consumption or drug abuse;
14. Patients treated with beta-blockers as regular use;
15. Patients treated with monoamine oxidase inhibitor, tricyclic antidepressants and Selective Serotonin Re-uptake Inhibitors (SSRIs), unless already taken at stable doses at the screening visit
16. Allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients;
17. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study;
18. Patients who received any investigational new drug within the last 12 weeks;
19. Patients with asthma exacerbations during the run-in period will also be excluded from the study.