EFFICACY AND TOLERABILITY OF BECLOMETHASONE DIPROPIONATE 100 µg + FORMOTEROL 6 µg pMDI VIA HFA-134a vs. FLUTICASONE 125 µg + SALMETEROL 25 µg pMDI

Clinical diagnosis of moderate to severe persistent asthma for at least 6 months, according to GINA revised version 2002 guidelines (11):

* Forced expiratory volume (FEV1) or peak expiratory flow rate (PEFR) ³ 50% and £ 80% of the predicted normal;

* Asthma not adequately controlled with the current therapies, defined as presence of daily asthma symptoms \> once a week and night-time asthma symptoms \> twice a month, and daily use of short-acting β2-agonists. These findings are to be based on recent medical history and are to be confirmed in the 2-week run-in period.

Treatment with inhaled corticosteroids at a daily dose ≤ 1000 μg of BDP or equivalent. The daily dose of inhaled corticosteroids taken at visit 1 will be assessed taking into account the following ratios between the doses of the different steroids: fluticasone propionate : BDP CFC = 1 : 2; budesonide : BDP CFC = 4 : 5; flunisolide : BDP CFC = 1 : 1. The ratios between inhaled steroids are irrespective of the formulations (i.e. spray aerosol or powder) used. When BDP is given in the new extra-fine HFA-134a formulation (as QVAR®, 3M Healthcare), the ratio with BDP CFC is set as 2 : 5. Therefore, the maximum allowed daily dose of inhaled corticosteroids at study entry will be: budesonide 800 μg, fluticasone propionate 500 μg, flunisolide 1000 μg, BDP 1000 mg, BDP HFA extra-fine 400 μg.

Positive response to the reversibility test in the screening visit, defined as an increase of at least 12% (or, alternatively, of 200mL) from baseline value in the measurement of FEV1 30 minutes following 2 puffs (2 ´ 100 µg) of inhaled salbutamol administered via pMDI. The reversibility test can be avoided in patients having a documented positive response in the previous 6 months.

A co-operative attitude and ability to be trained to correctly use the metered dose inhalers and to complete the diary cards.

Written informed consent obtained.

At the end of the 2-week run-in period, the presence of daily asthma symptoms (of at least mild intensity) and nighttime asthma symptom (of at least mild intensity) \> once a week, as well as of daily use of relief salbutamol is to be confirmed by reviewing the diary cards for run-in.

Current smokers or recent (less than one year) ex-smokers, defined as smoking at least 10 cigarettes/day;

History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe hypertension, cardiac arrhythmias;

Diabetes mellitus;

Percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass graft (CABG) during the previous six months;

Patients with an abnormal QTc interval value in the ECG test, defined as \> 450 msec in males or \> 470 msec in females;

Other haemodynamic relevant rhythm disturbances (including atrial flutter or atrial fibrillation with ventricular response, bradycardia (≤ 55 bpm), evidence of atrial-ventricular (AV) block on ECG of more than 1st degree;

Clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism, significant hepatic impairment, poorly controlled pulmonary (tuberculosis, active mycotic infection of the lung), gastrointestinal (e.g. active peptic ulcer), neurological or haematological autoimmune diseases;

Cancer or any chronic diseases with prognosis \< 2 years;

Pregnant or lactating females or females at risk of pregnancy, i.e. those not demonstrating adequate contraception (i.e. barrier methods, intrauterine devices, hormonal treatment or sterilization). A pregnancy test is to be carried out in women of a fertile age.

History of alcohol or drug abuse;

Patients treated with monoamine oxidase inhibitors, tricyclic antidepressants or beta-blockers as regular use;

Allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients;

Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study;

Patients who received any investigational new drug within the last 12 weeks;

Patients who have been previously enrolled in this study;

At the end of the run-in period, patients will not be admitted to the treatment period in the case of an increase of PEFR (L/sec) measured at the clinics at the end of the run-in period ³ 15% in respect of values measured at the start of the run-in period;

Patients with asthma exacerbations during the run-in period will also be excluded from the study.

What this study is about