Efficacy and Safety of 2 Doses of Tiotropium Via Respimat Compared to Placebo in Adolescents With Moderate Persistent Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: tiotropium Respimat low dose; placebo Respimat; tiotropium Respimat high dose
Intervention description: IMP; placebo representing comparator; IMP
Intervention MeSH terms: Tiotropium Bromide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 398.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The aim of the study is to evaluate efficacy and safety of a 48-week treatment with two doses
      of tiotropium bromide compared to placebo in adolescent patients with moderate persistent
      asthma. Efficacy and safety will be assessed by measuring lung function parameters and
      evaluating the effects on asthma exacerbations, on Quality of life, on health care resource
      utilisation an on the number of adverse events.
    

Eligibility criteria:

        Inclusion criteria:

          1. All patients and their parents (or legally accepted caregiver) must sign and date an
             informed consent consistent with ICH-GCP guidelines and local legislation prior to
             participation in the trial.

          2. Male or female patients between 12 and 17 years of age.

          3. All patients must have at least a 3 months history of asthma at the time of enrolment
             into the trial. The diagnosis of asthma has to be confirmed at visit 1 with a
             bronchodilator reversibility test.

          4. All patients must have been on maintenance treatment with inhaled corticosteroids at a
             stable medium dose for at least 4 weeks before Visit 1.

          5. All patients must be symptomatic (partly controlled) at Visit 1 (screening) and at
             randomisation defined by an Asthma Control Questionnaire (ACQ) mean score of more than
             or equal to 1.5.

          6. All patients must have a pre-bronchodilator FEV1 more than or equal to 60% and less
             than or equal to 90% of predicted normal at Visit 1. Variation of absolute FEV1 values
             of Visit 1 as compared to Visit 2 must be within ± 30%.

          7. All patients must have an increase in FEV1 of equal or above 12% and 200 mL after 400
             µg salbutamol (albuterol) at Visit 1. If patients in the lower age range (e.g., 12 to
             14 year olds) exhibit a very small total lung volume, positive reversibility testing
             might be based solely on the relative (12%) post-bronchodilator response.

          8. All patients should be never-smokers or ex-smokers who stopped smoking at least one
             year prior to enrolment.

          9. Patients should be able to use the Respimat® inhaler correctly.

         10. Patients must be able to perform all trial related procedures including technically
             acceptable spirometric manoeuvres.

        Exclusion criteria:

          1. Patients with a significant disease other than asthma.

          2. Patients with clinically relevant abnormal screening haematology or blood chemistry

          3. Patients with a history of congenital or acquired heart disease, and/or have been
             hospitalised for cardiac syncope or failure during the past year.

          4. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac
             arrhythmia requiring intervention or a change in drug therapy within the past year.

          5. Patients with malignancy for which the patient has undergone resection, radiation
             therapy or chemotherapy within the last five years.

          6. Patients with lung diseases other than asthma (e.g. Cystic Fibrosis). In case of
             ex-premature infants, a history of significant bronchopulmonary dysplasia will be
             regarded as exclusion criterion.

          7. Patients with known active tuberculosis.

          8. Patients with significant alcohol or drug abuse within the past two years.

          9. Patients who have undergone thoracotomy with pulmonary resection.

         10. Patients who are currently in a pulmonary rehabilitation program or have completed a
             pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit
             1).

         11. Patients with known hypersensitivity to anticholinergic drugs, Benzalkonium chloride
             (BAC), Ethylenediaminetetraacetic acis (EDTA) or any other components of the
             tiotropium inhalation solution.

         12. Pregnant or nursing adolescent female patients

         13. Sexually active female patients of child-bearing 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 long-acting anticholinergics (e.g. tiotropium
             -Spiriva) within four weeks prior to screening (Visit 1).

         16. Patients who are unable to comply with pulmonary medication restrictions prior to
             randomisation.

         17. Patients who have been treated with Anti-IgE treatment (Omalizumab Xolair) within the
             last 6 months prior to screening.

         18. Patients who have been treated with systemic (oral or intravenous) corticosteroids
             within 4 weeks prior to screening (Visit 1).

         19. Patients who have been treated with long-acting theophylline preparations within 2
             weeks prior to screening (Visit 1) or during the run-in period

         20. Patients who have been treated with other non-approved and according to international
             guidelines not recommended ¿experimental¿ drugs for routine asthma therapy.

         21. Patients with any acute asthma exacerbation or respiratory tract infection in the 4
             weeks prior to Visit 1.

         22. Patients requiring 10 or more puffs of rescue medication (salbutamol/albuterol) per
             day on more than 2 consecutive days during the run-in period.

         23. Patients who have previously been randomised in this trial or are currently
             participating in another study.

         24. Patients who are being treated with oral beta-blocker medication.

         25. Patients with a known narrow-angle glaucoma, or any other disease where
             anticholinergic treatment is contraindicated.

         26. Patients with renal impairment, as defined by a creatinine clearance less than 50
             mL/min/1.73 m2 Body Surface Area as calculated by Schwartz formula.