Efficacy and Safety of 2 Doses of Tiotropium Via Respimat in Adult Patients With Mild Persistent Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: placebo; tiotropium 2.5 mcg; tiotropium 5 mcg
Intervention description: To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler; To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler; To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via 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: 465.0
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
      compared to placebo over 12 week treatment period. Tiotropium inhalation solution will be
      delivered via Respimat inhaler and will be examined on top of maintenance inhaled
      corticosteroid treatment in patients with mild persistent asthma. Efficacy and safety will be
      assessed by measuring the effects on lung functions, effects on lung exacerbations, effects
      on asthma control and numbers 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 18 years or more at Visit 0 and 75 years or less at Visit
             0.

             All patients must have

          3. at least a 3 months history of asthma at the time of enrolment into the trial. The
             initial diagnosis of asthma must have been made before the patient's age of 40;

          4. a pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1)= 60% predicted and =
             90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 1
             (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.

          5. Patient's diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator
             reversibility (within 10 minutes pre and 15-30 minutes after 400 µg
             salbutamol/albuterol) resulting in a FEV1 increase of = 12% and = 200mL. If this is
             not achieved the reversibility test may be repeated once within two weeks.

          6. All patients must be symptomatic despite their current maintenance treatment with low
             doses of inhaled corticosteroids.

          7. All patients must be symptomatic at Visit 1 (screening) and Visit 2 as defined by an
             Asthma Control Questionnaire (ACQ) mean score of = 1.5.

          8. All patients must have been on maintenance treatment with a low, stable dose of
             inhaled corticosteroids for at least 4 weeks prior to Visit 1.

          9. Patients must be never-smokers or ex-smokers who stopped smoking at least one year
             prior to enrolment and who have a smoking history of less than 10 pack years ((see
             Appendix 10.3 for calculation).

         10. Patients must be able to use the Respimat® inhaler correctly.

         11. Patients must be able to perform all trial related procedures including technically
             acceptable pulmonary function tests and use of the e-Diary/peak flow meter
             (e-Diary-compliance of at least 80% is required; refer to Section 6.2.1 for
             instructions).

         12. Patients taking a chronic pulmonary medication allowed by the study protocol must be
             willing to continue this therapy for the entire duration of the study (exception:
             times of acute disease deterioration).

        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) 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 number 1.

          3. Patients requiring more than 10 puffs of rescue medication (salbutamol/albuterol MDI)
             per 24 hours on 2 consecutive days during the screening period.

          4. Patients with a recent history (i.e. six months or less) of Acute Coronary Syndrome
             (STEMI, Non-STEMI and Unstable Angina Pectoris).

          5. Patients who have been hospitalised for cardiac failure during the past year.

          6. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac
             arrhythmia requiring intervention or a change in drug therapy within the past year.

          7. Patients with lung diseases other than asthma (e.g. COPD).

          8. Patients with known active tuberculosis.

          9. 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.

         10. 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.

         11. Patients with significant alcohol or drug abuse on Investigator's assessment within
             the past two years.

         12. 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).

         13. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other
             components of the tiotropium inhalation solution.

         14. Pregnant or nursing woman, including female patients with positive beta-HCG test at
             Visit 1.

         15. Female patients of child-bearing potential not using highly effective method of birth
             control As defined in ICH (M3).

         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 oral or patch beta-adrenergics, systemic, i.e.
             oral or intravenous corticosteroids, 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 depot corticosteroids within six months prior to
             Visit 1 and/or during the screening period.

         19. Patients who have ever been treated with anti-IgE antibodies.

         20. Patients who have been treated with leukotriene modifiers, systemic anticholinergics,
             cromolyn sodium or nedocromil sodium and methylxanthines or phosphodiesterase 4
             inhibitors within two weeks prior to Visit 1 and/or during the screening period.

         21. Patients who have been treated with inhaled long acting beta adrenergics and long
             acting beta adrenergics combination products within four weeks prior to Visit 0 and/or
             during the screening period.

         22. Patients who have taken an investigational drug within four weeks or six half lives
             whichever is greater prior to Visit 1.

         23. Patients who have been treated with other non-approved and according to international
             guidelines not recommended, experimental drugs for routine asthma therapy (e.g.
             TNFalpha blockers, methotrexate, cyclosporin) within four weeks prior to Visit 1
             and/or during the screening period (period between Visit 1 and Visit 2).

         24. Patients with any asthma exacerbation or any respiratory tract infection in the four
             weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and
             Visit 2).

         25. Current participation in another trial.