Clinical trial NCT02182479 (phase 3, status: completed)
Conditions: asthma
ICD codes: J45.998, J82.83, J45.909, J45.991, J45.20, J45.30, J45.40
Drugs: berodual® via respimat®, high dose, berodual® via respimat®, low dose, berodual® via mdi, high dose, placebo respimat®, placebo mdi
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of bronchial asthma according to the ATS (American Thoracic Society)

          -  Age: 18 - 65 years

          -  Screening FEV1: 40 - 80 % of predicted normal. Predicted normal values will be based
             on the guidelines for standardised function testing of the European Community for Coal
             and Steel

          -  Airway obstruction reversibility: increase in FEV1 12% from baseline and ≥ 200 ml from
             baseline at 30 minutes after 2 puffs of Berodual® MDI

          -  Current non-smoker or ex-smoker (with a smoking history of ≤ 10 pack-years) with
             cessation of smoking ≥ 1 year prior to the screening visit

          -  Male or female patients

          -  Ability to be trained in proper use of MDI and RESPIMAT® devices

          -  Ability to perform technically satisfactory pulmonary function tests

          -  No hospital admission for an exacerbation and stable dosage of all pulmonary
             medication in the last four weeks (except for long acting β2 agonists)

          -  Willingness and ability to sign informed consent form prior to participation in the
             trial

        Exclusion Criteria:

          -  Patients with significant disease other than asthma, e.g. history of clinically
             significant cardiovascular, renal, neurological, hepatic or endocrine dysfunction. A
             clinically significant disease is defined as a disease which in the opinion of the
             investigator may either put the patient at risk because of participation in the study
             or which may influence the results of the study or the ability of the patient to
             participate in and complete the study

          -  History of myocardial infarction within the last year

          -  Tuberculosis with indication for treatment

          -  History of cancer within the last five years, excluding treated basal cell carcinoma

          -  Patients who have undergone thoracotomy for pulmonary resection of more than one
             bullae, or with subsequent impaired thoracic muscle performance leading to
             unsatisfactory lung function testing

          -  Current psychiatric disorders

          -  History of life threatening pulmonary obstruction, cystic fibrosis or bronchiectasis

          -  An upper or lower respiratory tract infection in the four weeks prior to the screening
             visit (= Visit 1) or during the 2-week run-in period

          -  Patients with clinically significant abnormal baseline haematology, blood chemistry or
             urinalysis, if the abnormality defines a disease listed as an exclusion criterion

          -  Patients with AST/ALT (aspartate amino transferase/alanine amino transferase)
             (SGOT/SGPT (serum glutamic oxaloacetic transaminase/serum glutamic pyruvic
             transaminase)) > 200%, bilirubin > 150% (except isolated bilirubin increase due to
             Gilbert's Syndrome), or creatinine > 125% of the upper limit of the normal range

          -  Intolerance to aerosolised fenoterol- or ipratropium-containing products, and/or
             hypersensitivity to any of the MDI ingredients

          -  Patients using oral corticosteroid medication at unstable (i.e. less than 4 weeks on a
             stable dose) or at a dose in excess of the equivalent of 10 mg prednisone per day or
             20 mg every other day

          -  Beta-blocker medication

          -  Patients who have taken an investigational drug one month or six half-lives (whichever
             is greater) prior to the screening visit

          -  History of drug abuse and/or alcoholism

          -  Pregnant or nursing women and women of childbearing potential or less than 2 years
             postmenopausal, who are not using medically approved means of contraception (oral
             contraceptives, intra-uterine devices or surgical Sterilisation)

          -  Previous participation in this study

          -  Patients who need more than 8 puffs of salbutamol (100 µg per puff) rescue medication
             on 3 or more consecutive days during the run-in period

          -  Severe bronchial asthma with frequent nocturnal asthma attacks or acute exacerbations
             induced by recurrent bronchial infections several times per year

          -  Patients with known hypersensitivity to anticholinergic drugs

          -  Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction

          -  Patients with known narrow-angle glaucoma

          -  Patients who did not fill in at least 80% of the diary in the run-in period for both,
             medication taken and peak expiratory flow rate (PEFR) measurements are considered not
             compliant