Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Severe Persistent Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Placebo; Tiotropium low dose mcg; Tiotropium high dose
Intervention description: 2 actuations once daily in the evening; 2 actuations once daily in the evening; 2 actuations once daily in the evening
Intervention MeSH terms: Tiotropium Bromide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 401.0
Sex: All
Minimum age: 6 Years
Maximum age: 11 Years
Healthy volunteers: No

Summary:

      The overall purpose of the trial is to evaluate efficacy and safety of tiotropium inhalation
      solution (2.5 mcg and 5 mcg) delivered via Respimat® inhaler once daily in the evening over
      12 weeks, compared to placebo, as add-on controller therapy on top of usual care in children
      (6 to 11 years old) with severe persistent asthma.
    

Eligibility criteria:

        Inclusion criteria:

        Inclusion criteria are:

          1. All patients' parent(s) (or legal guardian) must sign and date an informed consent
             prior to participation in the trial. In addition, an informed assent suitable for this
             age group has to be obtained from patients. A separate informed consent/assent is
             required for pharmacogenomic sampling.

          2. Male or female patients between 6 and 11 years of age.

          3. All patients must have at least a 6-month history of asthma.

          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 (partly controlled) at Visit 1 and prior to
             randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ-IA) mean
             score >= 1.5.

          6. All patients must have a pre-bronchodilator forced expiratory volume in one 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% 15 to 30 minutes after 200 mcg
             salbutamol/albuterol.

          9. Patients must be able to use the Respimat inhaler correctly.

         10. Patients must be able to perform all trial related procedures including technically
             acceptable pulmonary function tests and use of electronic diary/peak flow meter (diary
             compliance of at least 80% is required).

        Exclusion criteria:

        Exclusion criteria are:

          1. Patients with a significant disease other than asthma.

          2. Patients with a clinically relevant abnormal haematology or blood chemistry at
             screening.

          3. Patients with a history of congenital or acquired heart disease, or patients who 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 a malignancy for which the patient has undergone resection, radiation
             therapy or chemotherapy within the last five years.

          6. Patients with known active tuberculosis.

          7. Patients who have undergone thoracotomy with pulmonary resection.

          8. Patients who are currently in a pulmonary rehabilitation program or have completed a
             pulmonary rehabilitation program in the six weeks prior to Visit 1.

          9. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other
             components of the inhalation solution used with the Respimat inhaler.

         10. Pregnant or nursing female patients, including postmenarchal girls with a positive
             urine pregnancy test at Visit 1.

         11. Postmenarchal girls of child-bearing potential not using a highly effective method of
             birth control.

         12. Patients who have been treated with systemic corticosteroids within four weeks prior
             to Visit 1.

         13. Patients who have been treated with systemic beta-adrenergics within four weeks prior
             to Visit 1.

         14. Patients who have been treated with oral beta-blocker medication within four weeks
             prior to Visit 1 and/or during the screening period.

         15. Patients who have been treated with inhaled long-acting anticholinergics or systemic
             anticholinergic treatment within four weeks prior to Visit 1 and/or during the
             screening period, or who have been treated with inhaled short-acting anticholinergics
             within two weeks prior to Visit 1.

         16. Patients who have been treated with short-acting theophylline preparations within two
             weeks prior to Visit 1.

         17. Patients who have been treated with 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.

         18. Patients who have taken an investigational drug within six half lives according to the
             investigator's information, or four weeks (whichever is greater) prior to Visit 1
             and/or during the screening period.

         19. Patients who have previously been randomised in this trial or are currently
             participating in another trial.

         20. Patients with any acute asthma exacerbation or respiratory tract infection 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.

         21. Patients requiring six or more puffs of rescue medication per day on more than two
             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.

         22. Patients who are unable to comply with medication restrictions prior to Visit 1 and/or
             prior to Visit 2.

         23. Patients with a known narrow-angle glaucoma, or any other disease where
             anticholinergic treatment is contraindicated.

         24. Patients with moderate to severe renal impairment, as defined by a creatinine
             clearance <50 mL/min/1.73 m2 BSA, as tiotropium is a predominantly renally excreted
             drug.