Efficacy and Safety of CHF 1535 200/6µg in Not Adequately Controlled Asthmatic Patients

Inclusion Criteria

• Patient's written informed consent obtained prior to any study-related procedures;
• Male or female patients aged >=18;
• Patients with persistent asthma not optimally controlled (GINA 2010 'Management Approach Based on Control') on high doses of ICS (1000-2000 μg daily dose BDP non-extrafine or equivalent) or medium doses of ICS+LABA (500-1000 μg daily dose BDP non-extrafine or equivalent plus formoterol 24 μg or salmeterol 100 μg) at a stable dose for at least 4 weeks prior to screening; Equivalence to Medium dose High dose BDP non-extrafine 500-1000 μg > 1000-2000 μg BDP extrafine 200-400 μg > 400-800 μg Budesonide 400-800 μg > 800-1600 μg Ciclesonide 160-320 μg > 320-1280 μg Fluticasone 250-500 μg > 500-1000 μg Mometasone 400-800 μg > 800-1200 μg
• Patients with a FEV1 > = 40% and 0.75. Both of the above had to be met at screening and at the end of the run-in period;
• Presence of at least 7 available pre-dose morning PEF measurements in the run-in period;
• Patients with a cooperative attitude and ability to be trained to correctly use the pMDI and a portable electronic peak flow meter;
• For France only: only patients registered under a social welfare could be included in the study.

Exclusion Criteria

Patients were not enrolled in the study if one or more of the following criteria were present:

• Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake;
• Seasonal (intermittent) asthma or asthma occurring only during episodic exposure to an allergen or a chemical sensitiser;
• History of near fatal asthma or of a past hospitalisation for asthma in intensive care unit or of frequent exacerbations (3 or more asthma exacerbations/year) which, in the judgement of the Investigator, could have placed the patient at undue risk;
• Hospitalisation, emergency room (ER) admission or use of systemic corticosteroids for asthma exacerbation in the 4 weeks prior to the screening visit and during the run-in period;
• Lower respiratory tract infection in the 4 weeks before the screening visit;
• History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which could have interfered with data evaluation;
• Patients who suffered from Chronic Obstructive Pulmonary Disease (COPD) as defined by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines;
• Current smokers or ex-smokers with total cumulative exposure equal or more than 5 pack-years and/or who stopped smoking one year or less prior to screening visit;
• Any change in dose, schedule, formulation of ICS or ICS+LABAs in the 4 weeks prior to the screening visit;
• Patients who were treated with anti-IgE antibodies;
• Patients who were treated with long acting anti-cholinergics (tiotropium);
• Patients who used any of the following medications prior to the screening visit and had not met the specified minimum wash-out period:
• Short-acting β2-agonists: 6 hours;
• LABA: 12 hours;
• Fixed combinations of an anti-cholinergic and short-acting β2-agonist: 12 hours;
• Short-acting anti-cholinergic: 12 hours;
• Systemic corticosteroids: 4 weeks;
• Slow release corticosteroids: 12 weeks;
• Pregnant or lactating women or women at risk of pregnancy i.e. not using one or more of the following acceptable methods of contraception:
• Surgical sterilisation (e.g. bilateral tubal ligation, hysterectomy);
• Hormonal contraception (implantable, injectable, patch, oral);
• Double-barrier methods (any double combination of: intrauterine device, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) Post-menopausal women, i.e. women with at least 12 months of natural (spontaneous) amenorrhea or at least 6 months of spontaneous amenorrhea with documented serum follicle-stimulating hormone levels > 40 mIU/mL, could be enrolled. A serum pregnancy test was performed at the screening