Efficacy and Safety of 3 Doses of Tiotropium Compared to Placebo in Adolescents (12 to 17 Yrs) With Moderate Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Tiotropium bromide; tiotropium bromide; tiotropium bromide; Placebo
Intervention description: inhalation solution, dose of 1.25 mcg (2 puffs of 0.625 mcg); inhalation solution, dose of 2.5 mcg (2 puffs of 1.25 mcg); inhalation solution, dose of 5 mcg (2 puffs of 2.5 mcg); placebo inhalation solution
Intervention MeSH terms: Bromides; Tiotropium Bromide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Enrollment: 105.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The primary objective of this trial is to evaluate the efficacy and safety of tiotropium 1.25
      mcg (2 actuations of 0.625 mcg), tiotropium 2.5 mcg (2 actuations of 1.25 mcg) and tiotropium
      5 mcg (2 actuations of 2.5 mcg) once daily in the evening delivered by the Respimat inhaler
      in adolescents (12 to 17 yrs) with moderate persistent asthma, compared to placebo and on top
      of maintenance therapy with an inhaled corticosteroid controller medication. It is a
      randomised, double-blind, placebo-controlled Phase II trial with incomplete cross-over
      design. Patients need to be still symptomatic, i. e. not fully controlled with their
      maintenance treatment.
    

Eligibility criteria:

        Inclusion criteria:

          1. All patients and legally accepted caregiver(s) must sign and date an Informed Consent
             form consistent with Good Clinical Practice (GCP) guidelines of the International
             Conference on Harmonisation of Technical Requirements for Registration of
             Pharmaceuticals for Human Use (ICH) 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 and fulfill the
             diagnostic criteria of moderate persistent asthma, according to the current Global
             Initiative for Asthma (GINA) guidelines at the time of enrolment into the trial.

          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 prior
             to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean
             score of equal or above 1.5.

          6. All patients must have a pre-bronchodilator FEV1 above 60% and less than or equal 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%.

          7. All patients must have an increase in FEV1 of equal or above 12% and 200 mL 15 min.
             after 400 mcg 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, according to American Thoracic Society (ATS)
             standards and the use of the electronic diary/peak flow meter.

        Exclusion criteria:

          1. Patients with a significant disease other than asthma.

          2. Patients with a history of congenital or acquired heart disease, and/or have been
             hospitalised for cardiac syncope or failure during the past year.

          3. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac
             arrhythmia requiring intervention (e. g. pacemaker implantation) or a change in drug
             therapy within the past year.

          4. Patients with malignancy for which the patient has undergone resection, radiation
             therapy or chemotherapy within the last five years.

          5. Patients with lung diseases other than asthma, e.g. cystic fibrosis (CF). In case of
             ex-premature infants, a history of significant bronchopulmonary dysplasia (BPD) will
             be regarded as exclusion criterion

          6. Patients with significant alcohol or drug abuse within the past two years.

          7. Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride
             (BAC), ethylenediaminetetraacetic acid (EDTA) or any other components of the
             tiotropium inhalation solution.

          8. Pregnant or nursing adolescent female patients, including female patients with a
             positive Beta HCG (serum pregnancy) testing at screening (visit 1).

          9. Sexually active female patients of child-bearing potential not using a highly
             effective method of birth control.

         10. Patients with a known narrow-angle glaucoma, or any other disease where
             anticholinergic treatment is contraindicated.

         11. Patients with renal impairment, as defined by a creatinine clearance less than 50
             mL/min/1.73 m2 body surface area (BSA) as calculated by Schwartz Formula.