Triple in Asthma Dose Finding

Inclusion Criteria

For inclusion into the study, patients were required to fulfil all of the following criteria:

• Patient's written informed consent obtained prior to any study-related procedures;
• Male or female patients aged ≥18;
• Patients with uncontrolled asthma on 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; Drug* Medium daily dose BDP non-extrafine >500 - 1000 μg BDP extrafine >250 - 500 μg Budesonide >400 - 800 μg Ciclesonide >160 - 320 μg Fluticasone >250 - 500 μg Mometasone ≥400 μg - 3), acute ischemic heart disease in the last year prior to study Screening, history of sustained cardiac arrhythmias or sustained and nonsustained cardiac arrhythmias diagnosed in the last 6 months (sustained means lasting more than 30 seconds and or ending only with external action, and or leads to hemodynamic collapse; non-sustained means > 3 beats 450 millisecond (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, would have prevented use of anticholinergic agents;
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may have increased the risk associated with study participation or study drug administration and, in the judgment of the Investigator, would have made the patient inappropriate for entry into this study, 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 ß2-agonists, inhaled corticosteroids, anti-cholinergics or propellant gases/excipients;
• Patients with major surgery in the 3 months prior to Screening visit and/or planned surgery during the trial;
• Patients treated with non-potassium sparing diuretics (association with potassium sparing diuretics was allowed), non-selective β-blocking drugs, 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 were receiving any therapy that could have interfered with the study drugs according to Investigator's opinion.

At the Screening visit (V1), all the above-mentioned exclusion criteria were checked. At the Randomisation visit (Visit P1D1 [V2], the following exclusion criteria were re-checked: 1, 3, 4, 5, 13, 16, 17, 19, 20, 24 and 27.