Study on BI 54903 (Inhaled Corticosteroid) Administered Once Daily or Twice Daily Via Respimat Inhaler in Patients With Asthma Inadequately Controlled on Short Acting Beta-2 Agonist (SABA) Therapy Alone
Study on BI 54903 (Inhaled Corticosteroid) Administered Once Daily or Twice Daily Via Respimat Inhaler in Patients With Asthma Inadequately Controlled on Short Acting Beta-2 Agonist (SABA) Therapy Alone
The aim of this study is to assess and compare efficacy and safety of BI 54903 at doses of
 very low dose twice daily (b.i.d) and low dose once daily (evening dosing) and placebo over
 an 12-week treatment period in asthmatic patients aged 12 to 65 years inadequately controlled
 on short acting beta-2 agonist (SABA) therapy alone as demonstrated by a decrease in forced
 expiratory volume in 1 second (FEV1) (not less than 10 %, and equal to or less than 25%) and
 an Asthma Control Questionnaire (ACQ-6) of not less than 1.5 at time of randomisation.
Inclusion criteria:

 To enter run-in following completion of pre-screening period:

 1. All patients must sign and date an Informed Consent Form (ICF) at Visit 0 consistent
 with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP)
 guidelines and local legislation prior to participation in trial, which includes
 medication washout and restrictions

 2. Male and female patients aged at least 12 to 65 years.

 3. All patients must have a history of asthma diagnosed by a physician for at least three
 months at the time of enrolment into the trial according to the 2009 Global Initiative
 for Asthma (GINA) Guidelines. The initial diagnosis of asthma must have been made
 before the age of 40 years.

 4. All patients must be on a maintenance treatment with either medium-dose inhaled
 corticosteroids (ICS) plus long acting beta-2 agonist (LABA) or high-dose ICS without
 LABA, stable for at least six weeks prior to Visit 1.

 5. All patients must have a pre-bronchodilator forced expiratory volume in 1 second
 (FEV1) of not less than 60 to 90% of predicted normal and an Asthma Control
 Questionnaire (ACQ-6) mean score of less than 1.5 at the pre-screening Visit 1.

 6. Patients must be never-smokers or ex-smokers with a smoking history of less than10
 pack-years and smoking cessation at least one year prior to screening .

 7. Patients must be able to use Respimat® inhaler and metered dosed inhaler (MDI)
 correctly

 8. Patients must be able to perform all trial-related procedures including technically
 acceptable pulmonary function tests and electronic pear expiratory flow (PEF)
 measurements, and must be able to maintain records during the study period as required
 in the protocol.

 To enter treatment period following additional criteria have to be met (at
 randomisation visit):

 9. All patients must have an improvement in FEV1 not less than 12 % above baseline and an
 absolute change of at least 200 mL within 15-30 min after administration of 400 mcg
 salbutamol/albuterol hydroflouroalkane (HFA) MDI., as demonstrated at Visit 1 or
 during one of the visits during the run-in period.

 10. During the run-in period (at the same clinic visit) all patients must be both
 symptomatic (ACQ-6 mean score equal to or greater than 1.5) and have shown a decrease
 in morning pre-bronchodilator FEV1 not less than 10% and less than or equal to 25%
 from pre-screening baseline FEV1 at Visit 2.

 Exclusion criteria:

 1. Patients with significant pulmonary disease other than asthma or other significant
 medical conditions (as determined by medical history, examination and clinical
 investigations at screening) that may, in the opinion of the investigator, result in
 any of the following: (i) put the patient at risk because of participation in this
 trial or (ii) influence the results of the trial or (iii) cause concern regarding the
 patient's ability to participate in the trial.

 2. Patients with a clinically relevant, abnormal screening haematology and/or blood
 chemistry finding, if the abnormality indicates a significant disease as defined in
 exclusion criterion no. 1.

 3. Patients with a history of upper or lower respiratory tract infection (URTI/LRTI) in
 the past four weeks prior to the pre-screening Visit 1, and during pre-screening and
 run-in periods.

 4. Patients with any exacerbation of their underlying asthma during the eight weeks prior
 to the pre-screening Visit 1.

 5. Patients with active allergic rhinitis requiring treatment with systemic
 corticosteroids.

 6. Any of the following criteria are met during the pre-screening / run-in period (Visits
 1 - 6):

 1. in clinic pre-bronchodilator FEV1 % predicted less than 40%,

 2. more than 12 puffs rescue salbutamol/albuterol HFA MDI per day for > 2
 consecutive days,

 3. exacerbation of asthma.

 7. Patients with a history of pneumonectomy or who are planning to undergo thoracotomy
 for any reason.

 8. Patients who are currently in a pulmonary rehabilitation program or have completed a
 pulmonary rehabilitation program in the six weeks prior to the first screening visit
 1.

 9. Patients with two or more hospitalizations for asthma within the previous 12 months.

 10. Patients with a recent history of myocardial infarction during the last twelve months
 or known coronary heart disease that requires treatment

 11. Patients with a history of hospitalisation due to heart failure in the past twelve
 months

 12. Patients with myocarditis or any unstable or life-threatening cardiac arrhythmia or
 cardiac arrhythmia requiring intervention or a change in drug therapy within the past
 year

 13. Patients with significant alcohol or drug abuse in the opinion of the investigator
 within the past two years

 14. Patients with rheumatoid arthritis or other systemic diseases that require immune
 system modulating treatment

 15. Patients suffering from or with a history of glaucoma, increased intraocular pressure,
 and/or cataracts

 16. Pregnant or nursing women

 17. Women of childbearing potential not using a highly effective method of birth control.

 18. Patients who have been treated with anti-IgE-antibodies (e.g. omalizumab - Xolair®) or
 other immune system modulating antibodies such as TNF alpha blockers within six months
 prior to Visit 1.

 19. Patients who have been treated with the following drugs during the past four weeks
 prior to Visit 1 or are foreseen to need this during the study:

 1. Non-selective ß-blockers (topical cardio-selective beta-blocker eye medications
 for non-narrow angle glaucoma are allowed),

 2. Oral or other systemic corticosteroids,

 3. Oral beta-agonists,

 4. Changes in allergen desensitisation therapy in last 6 months,

 5. Immune system modulating agents such as methotrexate or cyclosporine,

 6. Inhibitors of cytochrome P450 3A4 such as antifungals (e.g. ketoconazole,
 itraconazole), antibiotics (e.g. erythromycin) or antiretroviral drugs.

 20. Patients who have been treated with leukotriene modifiers, cromones or theophylline
 within two weeks prior to Visit 1.

 21. Patients who have been treated with tiotropium within 3 weeks prior to Visit 1.