Efficacy and Safety of Tiotropium and Salmeterol in Moderate Persistent Asthma Patients Homozygous for B16-Arg/Arg
Condition: Asthma
MeSH terms: Asthma
Intervention: Tiotropium bromide; Placebo; Salmeterol xinafoate
Intervention MeSH terms: Bromides; Tiotropium Bromide; Salmeterol Xinafoate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Parallel Assignment
Enrollment: 388.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This is a 16 week multicentre, multinational, randomised, double-blind, double-dummy,
      placebo-controlled, parallel group study to evaluate the long-term efficacy and safety of
      tiotropium compared to salmeterol in moderate persistent asthmatic (GINA step 3) patients
      homozygous for arginine at the 16th amino acid position of the beta-adrenergic receptor
      (ADRB2). Following an initial 4-week run-in period on salmeterol MDI patients will be
      randomised into the 16 week double-blind treatment period in which they receive either
      tiotropium once daily administered from the Respimat inhaler or salmeterol twice daily
      administered from the hydrofluoro-alkane Metered Dose Inhaler (MDI), or placebo twice daily.
      After the 16 week treatment period all patients will receive salmeterol MDI twice daily for
      four weeks.

      The patients perform daily morning and evening peak flow (PEF) and Forced Expiratory Volume
      in the First Second (FEV1) measurements with an electronic peak flow meter throughout the
      study. Daily data on asthma control and use of rescue medication are recorded using an
      electronic diary included in the electronic peak flow meter. On study visits the Mini-Asthma
      Quality of Life Questionnaire (Elizabeth Juniper) is administered, pulse and blood pressure
      and pre-dose pulmonary function testing (FEV1 and Forced Vital Capacity) are performed.
    

Eligibility criteria:

        Inclusion_Criteria:

          1. Patients homozygous for arginine at the 16th amino acid position of the beta2
             adrenergic receptor (B16 Arg/Arg)

          2. All patients must sign and date an Informed Consent Form for the study prior to
             participation in the trial

          3. Male or female outpatients with at least 18 years of age, but not older than 65 years

          4. Patients must have a documented history of asthma

          5. Patients must be current non-smokers or ex-smokers with a cigarette smoking history of
             <10 pack-years

          6. Patients must be on a maintenance treatment with inhaled corticosteroids with a total
             daily dose of 400 - 1000 mcg budesonide or equivalent

        Exclusion_Criteria:

          1. Patients with a significant disease other than asthma

          2. Patients with a recent history (i.e., six months or less) of myocardial infarction

          3. Patients who have been hospitalized for heart failure (New York Heart Association
             class III or IV) within 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. Patients with treated basal cell
             carcinoma are allowed.

          6. Patients with a diagnosis of chronic obstructive pulmonary disease (COPD)

          7. Patients with a history of life threatening pulmonary obstruction, or a history of
             cystic fibrosis or clinically evident bronchiectasis

          8. Patients with known active tuberculosis

          9. Patients who have undergone thoracotomy with pulmonary resection.

         10. Patients who have completed a pulmonary rehabilitation program in the six weeks prior
             to visit 1 or patients who are currently in a pulmonary rehabilitation program that
             will not be maintained throughout the duration of the study.