Efficacy of LAMA Added to ICS in Treatment of Asthma (ELITRA)

Inclusion Criteria

• Patient's written informed consent obtained prior to any study related procedures;
• Male or female patients aged ≥18 and ≤75 years;
• History of asthma ≥5 year and diagnosed before the age of 40 years;
• Patients with uncontrolled asthma on low medium doses of ICS (200 - 1000 μg daily dose BDP non-extrafine or estimated clinical comparable dose) at a stable dose for at least 4 weeks prior to Screening visit;
• Patients with a pre bronchodilator FEV1 ≥40% and 3), acute ischemic heart disease in the last year prior to study Screening, history of sustained cardiac arrhythmias or sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months (sustained means lasting more than 30 seconds or ending only with external action, or leads to hemodynamic collapse; non-sustained means >5 beats 450 ms for males or QTcF >470 ms for females at Screening or at Randomisation visits;
• Medical diagnosis of narrow angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that, in the opinion of the Investigator, prevented use of anticholinergic agents;
• Unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; with moderate to severe renal impairment (known creatinine clearance of ≤50 mL/min); uncontrolled gastrointestinal disease (e.g. active peptic ulcer); uncontrolled neurological disease; uncontrolled haematological disease; uncontrolled autoimmune disorders, or other laboratory abnormality that may have increased the risk associated with study participation or study medications administration and, in the judgment of theInvestigator, made the patient inappropriate for entry into this study, or placed the patients at undue risk or potentially compromised the results or interpretation of the study;
• Patients having received a live attenuated virus vaccination within two weeks prior to Screening or during the run-in (inactivated influenza vaccination was acceptable provided it was not administered less than 48 hours prior to Screening);
• Patients mentally or legally incapacitated;
• Patients with a history of alcohol or drug abuse;
• Patients with known intolerance/hypersensitivity or contra indication to treatment with β2 agonists, inhaled corticosteroids, anti cholinergics or propellant gases/excipients;
• Patients with major surgery in the 3 months prior to Screening visit or planned surgery during the trial;
• Patients treated with anti IgE antibodies;
• Patients treated with non-potassium sparing diuretics (unless administered as a FDC with a potassium conserving drug), non-selective beta blocking drugs (except if taken at stable regimen for at least 2 months before Screening), quinidine, quinidine like anti arrhythmics, or any medication with a QTc prolongation potential or a history of QTc prolongation;
• Patients treated with monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants;
• Patients who are receiving any therapy that could have interfered with the study medications according to Investigator's opinion. At the Screening visit (V1), all the above mentioned exclusion criteria were checked. At the Randomisation visit (V2), the following exclusion criteria were re-checked: 1, 2, 3, 4, 5, 12, 15, 16, 18, 19, 23 and 27.