Evaluation of Tiotropium 2.5 and 5 µg Once Daily Delivered Via the Respimat Inhaler Compared to Placebo in Patient With Moderate to Severe Persistent Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Tiotropium Respimat; Placebo Respimat; Tiotropium Respimat
Intervention description: Tiotropium high dose once daily delivered with Respimat inhaler; Tiotropium placebo once daily delivered with Respimat inhaler; Tiotropium low dose once daily delivered with Respimat inhaler
Intervention MeSH terms: Tiotropium Bromide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 285.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The aim of this trial is to evaluate the safety and efficacy of 2.5 and 5 µg tiotropium over
      a 52-week treatment period as compared to placebo. 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 to severe persistent asthma.
      Efficacy and safety will be assessed by measuring effects on lung function, effects on asthma
      exacerbations, effects on asthma control, and number of adverse events.
    

Eligibility criteria:

        Inclusion criteria:

          1. All patients including the patients under age (under 20 years old) must sign and date
             an Informed Consent Form consistent with ICH-GCP guidelines and Good Clinical Practice
             (GCP) 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 (PFT) at Visit 1]. Regarding patients under age, a guardian or
             a legally authorised representative must also sign and date an Informed Consent Form.

          2. Male or female outpatients aged at least 18 years but not more than 75 years at Visit
             0.

          3. All patients must have at least a 12-week history of asthma at the time of enrolment
             (Visit 0) 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 (15-30 minutes after 400 µg salbutamol) resulting in a Forced Expiratory
             Volume in one second (FEV1) increase of at least 12% and at least 200 mL .

          6. All patients must have been on maintenance treatment with a medium, stable dose of
             inhaled corticosteroids (ICS) [alone or in a fixed combination with a Long-acting
             beta-adrenergic (LABA)] for at least 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. Patients must be never-smokers or ex-smokers who stopped smoking at least one year (52
             weeks) prior to enrolment (Visit 0) and who have a smoking history of less than 10
             pack years.

         10. Patients must be able to use the Respimat inhaler correctly, which is judged at the
             discretion of the investigator..

         11. Patients must be able to perform all trial related procedures including technically
             acceptable PFTs and use of electronic diary (eDiary)/peak flow meter, which is judged
             at the discretion of the investigator.

        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 no 1.

          3. Patients with a recent history (i.e. 6 months or less) of myocardial infarction prior
             to Visit 0.

          4. Patients who have been hospitalised for cardiac failure during the past year prior to
             Visit 0.

          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
             prior to Visit 0.

          6. Patients with lung diseases other than asthma (e.g. COPD).

          7. Patients with known active tuberculosis.

          8. Patients with malignancy and/or patients who have undergone resection, radiation
             therapy or chemotherapy for malignancy within the last 5 years prior to Visit 0.
             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, which is judged at the discretion of
             the investigator, within the past 2 years prior to Visit 0.

         11. Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride
             (BAC), ethylenediaminetetraacetic acid (EDTA), or any other components of the study
             medication delivery systems.

         12. Pregnant or nursing women.

         13. Women of childbearing potential not using a highly effective method of birth control.

         14. Patients who have taken an investigational drug within 4 weeks prior to Visit 1.

         15. 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.

         16. 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.

         17. Patients who have been treated with oral beta-adrenergics within four weeks prior to
             Visit 1 and/or during the Screening period.

         18. Patients who have been treated with systemic corticosteroids within four weeks prior
             to Visit 1 and/or during the screening period.

         19. 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.

         20. 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.

         21. Patients with any asthma exacerbation or any respiratory tract infection in the four
             weeks prior to Visit 1 and/or during the screening period.

         22. Patients who are currently participating in another trial.

         23. Patients with narrow-angle glaucoma and/or micturition disorder due to prostatic
             hyperplasia.

         24. Patients with below 80% of the eDiary completion compliance on Visit 2 (diary
             compliance of at least 80% is required).