Evaluation of Tiotropium 2.5 and 5 mcg Once Daily Delivered Via the Respimat® Inhaler Compared to Placebo and Salmeterol HydroFluoroAlkane (HFA) Metered Dose Inhaler (MDI) (50 mcg Twice Daily) in Patient With Moderate Persistent Asthma II
Condition: Asthma
MeSH terms: Asthma
Intervention: placebo; placebo; placebo; tiotropium Respimat® low dose; placebo; tiotropium Respimat® high dose; 50 mcg salmeterol HFA MDI; placebo
Intervention description: Placebo that represents BI drug; Placebo that represents comparator; Placebo that represents comparator; IMP; Placebo that represents BI drug; IMP; Active comparator; Placebo that represents comparator
Intervention MeSH terms: Tiotropium Bromide; Salmeterol Xinafoate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 1032.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The aim of this trial is to evaluate the efficacy and safety of 2.5 and 5 mcg tiotropium over
      a 24-week treatment period as compared to placebo and salmeterol (50 mcg twice daily).
      Tiotropium inhalation solution delivered by the Respimat® inhaler will be examined on top of
      maintenance treatment with inhaled corticosteroid controller medication in patients with
      moderate persistent asthma. Efficacy and safety will be assessed by measuring effects on lung
      function, effects on asthma exacerbations, effects on quality of life, effects on asthma
      control, effects on health care resource utilisation, and number of adverse events.
    

Eligibility criteria:

        Inclusion criteria:

          1. All patients must sign and date an Informed Consent Form consistent with International
             Conference on Harmonisation - Good Clinical Practice (ICH-GCP) guidelines 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).

          2. Male or female patients aged at least 18 years but not more than 75 years.

          3. 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 5.

          4. The initial diagnosis of asthma must have been made before the patient's age of 40.

          5. The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator
             reversibility (15 minutes after 400 mcg salbutamol (albuterol)) resulting in a Forced
             Expiratory Volume in one second (FEV1) increase of at least 12% and at least 200mL.

          6. All patients must have been on maintenance treatment with a medium, stable dose of
             inhaled corticosteroids for at least for 4 weeks prior to Visit 1. 7. 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 at least 1.5.

        8. All patients must have a pre-bronchodilator FEV1 at least 60% and less than or equal to
        90% of predicted normal at Visit 1.

        9. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2
        (pre-dose) must be within ± 30%.

        10. 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.

        11. Patients must be able to use the Respimat® inhaler and metered dose inhaler correctly.

        12. Patients must be able to perform all trial related procedures including technically
        acceptable pulmonary function tests and use of electronic diary/peak flow meter.

        Exclusion criteria:

          1. Patients with a significant disease other than asthma. A significant disease is
             defined as a disease which, in the opinion of the investigator, may (i) put the
             patient at risk because of participation in the trial, or (ii) influence the results
             of the trial, or (iii) cause concern regarding the patient's ability to participate in
             the trial.

          2. 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.

          3. Patients with a recent history (i.e. six months or less) of myocardial infarction.

          4. Patients who have been hospitalised for cardiac failure during the past year.

          5. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac
             arrhythmia requiring intervention or a change in drug therapy within the past year.

          6. Patients with lung diseases other than asthma (e.g. Chronic Obstructive Pulmonary
             Disease (COPD)).

          7. Patients with known active tuberculosis.

          8. Patients with malignancy for which the patient has undergone resection, radiation
             therapy or chemotherapy within the last five years. Patients with treated basal cell
             carcinoma are allowed.

          9. 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.

         10. Patients with significant alcohol or drug abuse within the past two years.

         11. Patients who are currently in a pulmonary rehabilitation program or have completed a
             pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening).

         12. Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride
             (BAC), ethylenediamineteraacetic acid (EDTA), salmeterol xinafoate or any other
             components of the study medication delivery systems.

         13. Pregnant or nursing woman.

         14. Women of childbearing potential not using a highly effective method of birth control.

         15. Patients who have taken an investigational drug within four weeks prior to Visit 1.

         16. Patients who have been treated with beta-blocker medication within four weeks prior to
             Visit 1 and/or during the screening period. Topical cardio-selective beta-blocker eye
             medications for non-narrow angle glaucoma are allowed.

         17. 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.

         18. Patients who have been treated with oral or patch beta-adrenergics within four weeks
             prior to Visit 1 and/or during the Screening period.

         19. Patients who have been treated with oral corticosteroids within four weeks prior to
             Visit 1 and/or during the screening period.

         20. Patients who have been treated with anti-IgE antibodies, e.g. omalizumab (Xolair®),
             within 6 months prior to Visit 1 and/or during the screening period.

         21. Patients who have been treated with cromone within two weeks prior to Visit 1 and/or
             during the screening period.

         22. Patients who have been treated with methylxanthines or phosphodiesterase 4 inhibitors
             within two weeks prior to Visit 1 and/or during the screening period.

         23. Patients who have been treated with other non-approved and according to international
             guidelines not recommended "experimental" drugs for routine asthma therapy within four
             weeks prior to Visit 1 and/or during the screening period.

         24. Patients with any asthma exacerbation or any respiratory tract infection iin the four
             weeks prior to Visit 1 and/or during the screening period.

         25. Patients who have previously been randomised in this trial or in the respective twin
             trial (205.418) or are currently participating in another trial.