Efficacy and Safety of 2 Doses of Tiotropium Respimat Compared to Placebo in Adolescents With Severe Persistent Asthma

Inclusion criteria:

1. All patients and their parent(s) (or legally accepted representative) must sign and
date respectively an informed assent and an informed consent consistent with
International Conference on Harmonisation - Harmonised Tripartite Guideline for Good
Clinical Practice (ICH-GCP) guidelines and local legislation prior to the patient's
participation in the trial. A separate informed consent/assent is required for
pharmacogenomic sampling.

2. Male or female patients between 12 and 17 years of age (at date of informed
consent/assent).

3. All patients must have at least a 3-month history of asthma at the time of enrolment
into the trial.

4. All patients must have been on maintenance treatment with an inhaled corticosteroid
either at stable high dose in combination with another controller medication, OR at
stable medium dose in combination with two other controller medications, for at least
4 weeks before Visit 1.

5. 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.

6. All patients must have a pre-bronchodilator Forced Expiratory Volume in 1 second
(FEV1) = 60% and = 90% of predicted normal at Visit 1.

7. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator, considered as 100%)
as compared to Visit 2 (pre-dose) must be within ± 30%.

8. All patients must confirm the diagnosis of asthma by bronchodilator reversibility at
Visit 1, resulting in an increase in FEV1 of = 12% and = 200 mL 15 to 30 minutes
after 400 µg salbutamol (albuterol). If patients in the lower age range (e.g. 12 to
14 year old patients) exhibit a very small total lung volume, positive reversibility
testing might be based solely on the relative (=12%) post-bronchodilator response.

9. All patients must be never-smokers or ex-smokers who stopped smoking at least one
year prior to enrolment.

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 spirometric manoeuvres according to American Thoracic Society/ European
Respiratory Society (ATS/ERS) standards and use of the electronic diary/peak flow
meter (diary compliance of at least 80% is required).

Exclusion criteria:

1. Significant disease other than asthma.

2. Abnormal haematology or blood chemistry.

3. History of heart disease, and/or hospitalised for cardiac syncope or failure.

4. Any unstable or life-threatening or requiring intervention or cardiac arrhythmia.

5. Malignancy for which the patient has undergone resection, radiation therapy or
chemotherapy.

6. Active tuberculosis.

7. Alcohol or drug abuse.

8. Thoracotomy with pulmonary resection.

9. Pulmonary rehabilitation program.

10. Hypersensitivity to anticholinergic drugs, or any components of the study medication
delivery system.

11. Pregnant or nursing adolescent female patients.

12. Female patients of child-bearing potential not using a highly effective method of
birth control.

13. Investigational drug within four weeks or six half lives prior to Visit 1.

14. Long-acting anticholinergics within four weeks prior to Visit 1.

15. Systemic corticosteroids at a high dose or at a not stable low dose within four weeks
prior to Visit 1.

16. Leukotriene modifiers if not stabilised for at least four weeks prior to Visit 1.

17. Long-acting theophylline preparations if not stabilised for at least two weeks prior
to Visit 1.

18. Anti Immunoglobulin E (Anti-IgE) treatment if not stabilised for at least six months
prior to Visit 1.

19. Cromones if not stabilised within four weeks prior to Visit 1.

20. Oral beta-blocker medication within four weeks prior to Visit 1.

21. Systemic oral or i.v. or s.c. beta-adrenergics within four weeks prior to Visit 1.

22. Other non-approved and according to international guidelines not recommended
experimental drugs for routine asthma therapy within four weeks prior to Visit 1.

23. Any acute asthma exacerbation or respiratory tract infection in the four weeks prior
to Visit 1and/or in the four weeks prior to Visit 2. In case of an asthma
deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks
prior to Visit 2, the visit must be postponed.

24. Randomised in this trial or currently participating in another trial.

25. Narrow-angle glaucoma, or any other disease where anticholinergic treatment is
contraindicated.

26. Moderate to severe renal impairment.

27. Patients requiring 10 or more puffs of rescue medication per day on more than 2
consecutive days in the four weeks prior to Visit 1 and/or in the four weeks prior to
Visit 2. In case of an asthma deterioration occurring in the four weeks prior to
Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.