Randomised, Double- Blind, Cross-over Efficacy and Safety Comparison of Three Different Doses of Tiotropium Administered Once Daily Versus Placebo in Patients With Moderate Persistent Asthma.

Inclusion criteria

• All patients must sign and date an Informed Consent Form consistent with the Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1).
• Male or female patients aged between 18 and 75 years (at date of informed consent).
• All patients must have at least a 3 month history of asthma at the time of enrolment into the trial. The diagnosis should be confirmed at Visit 1 by fulfilling inclusion criterion no. 5.
• The initial diagnosis of asthma must have been made before the patient's age of 40.
• The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (15 to 30 minutes after 4 puffs of 100 µg salbutamol) resulting in a Forced Expiratory Volume in one second (FEV1) increase of = 12% and = 200mL.
• All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids (alone or in a fixed combination with a long acting or short acting beta agonist [LABA or SABA]) for at least 4 weeks prior to Visit 1.
• All patients must be symptomatic at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean score of = 1.5.
• All patients must have a pre-bronchodilator FEV1 = 60% and = 90% of predicted normal at Visit 1. Predicted normal values will be calculated according to the European Community for Steel and Coal (ECSC).
• Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.
• Patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment (Visit 0) and who have a smoking history of less than 10 pack years.
• Patients must be able to use the Respimat® inhaler correctly.
• Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of electronic diary/peak flow meter (diary compliance of at least 80% is required).

Exclusion criteria

• Patients with a significant disease other than asthma.
• Patients with a clinically relevant abnormal screening (Visit 1) haematology or blood chemistry if the abnormality defines a significant disease as defined in exclusion criterion 1.
• Patients with a recent history (i.e. six months or less) of myocardial infarction.
• Patients who have been hospitalised for cardiac failure during the past year.
• Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.
• Patients with lung diseases other than asthma.
• Patients with known active tuberculosis.
• Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
• Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion no. 1.
• Patients with known moderate to severe renal impairment.
• Patients with known narrow angle glaucoma or any other disease where anticholinergic treatment is contraindicated.
• Patients with significant symptomatic prostatic hyperplasia or bladder-neck obstruction. Patients whose symptoms are controlled on treatment may be included.
• Patients with significant alcohol or drug abuse within the past two years (to the discretion of the investigator).
• Patients who are currently in a pulmonary rehabilitation program or have completed pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening) or who will start a rehabilitation program during the study.
• Patients with known hypersensitivity to anticholinergic drugs, Benzalkonium chloride (BAC), Ethylenediaminetetraacetate (EDTA) or any other components of the study medication delivery system (Respimat®/ tiotropium inhalation solution).
• Pregnant or nursing woman.
• Women of childbearing potential not using a highly effective method of birth control.
• Patients who have taken an investigational drug within four weeks prior to Visit 1.
• Patients who have been treated with beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2). Topical cardio-selective beta-blocker eye medications for non-arrow angle glaucoma are allowed.
• Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®) within four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).
• Patients who have been treated with oral or patch beta-adrenergics within four weeks prior to Visit 1 and/or during the Screening period (period between Visit 1 and Visit 2)
• Patients who have been treated with oral corticosteroids within four weeks prior to Visit 1 and/or during the screening period.
• Patients who have been treated with anti-Immunoglobuline E (anti-IgE) antibodies, e.g. omalizumab, within 6 months prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).
• Patients who have been treated with cromone within two weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).
• Patients who have been treated with methylxanthines or phosphodiesterase 4 inhibitors within two weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).
• Patients who have been treated with other non-approved and according to international guidelines not recommended experimental drugs for routine asthma therapy (e.g. Tumor Necrosis Factor (TNF)-alpha blockers, methotrexate, cyclosporin) within four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).
• Patient with any asthma exacerbation or respiratory tract infection in the 4 weeks prior to visit 1 and/or during the screening period.