Study on BI 54903 (Inhaled Corticosteroid) Administered Twice Daily Via Respimat Inhaler in Patients With Asthma Inadequately Controlled on Medium Dose Inhaled Corticosteroid (ICS).
Condition: Asthma
MeSH terms: Asthma
Intervention: Placebo; Fluticasone propionate; BI 54903
Intervention description: Placebo matching fluticasone propionate HFA MDI; Fluticasone propionate HFA MDI; BI 54903 via Respimat inhaler
Intervention MeSH terms: Fluticasone; Xhance
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 9.0
Sex: All
Minimum age: 12 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The aim of the study is to assess and compare efficacy and safety of BI 54903 at three
      different dosages (b.i.d)., fluticasone propionate hydrofluoroalkane (HFA) metered dose
      inhaler (MDI) at a dose of 440 mcg b.i.d and low dose fluticasone propionate 88 mcg b.i.d.
      over an 8-week treatment period in asthmatic patients aged 12 to 65 years inadequately
      controlled medium dose ICS therapy as demonstrated by a decrease in forced expiratory volume
      in one second (FEV1) range 10 to 25 % and an asthma control questionnaire-6 (ACQ-6) equal or
      greater than 1.5 at time of randomisation.
    

Eligibility criteria:

        Inclusion criteria:

          1. Must be willing and able to give informed consent.

          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 high-dose ICS with long-acting
             beta 2-agonist (LABA), stable for at least six weeks prior to Visit 1

          5. All patients must have a pre-bronchodilator FEV1 of not less than 60 to 90% of
             predicted normal and an ACQ-6 mean score of less than 1.5 at the pre-screening Visits
             1and 2.

          6. Patients must be never-smokers or ex-smokers with a smoking history of less than 10
             pack-years and smoking cessation at least one year prior to screening .

          7. Patients must be able to use Respimat® inhaler and MDI correctly

          8. Patients must be able to perform all trial-related procedures including technically
             acceptable pulmonary function tests and electronic peak 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:

          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 HFA MDI as demonstrated at Visit 1 or during one of the visits
             during 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 respiratory tract infection (URTI) or lower
             respiratory tract infection (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):

               -  in clinic pre-bronchodilator FEV1 % predicted less than 40%,

               -  more than 12 puffs rescue salbutamol/albuterol HFA MDI per day for > 2
                  consecutive days,

               -  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 tumor necrosis factor-alpha blockers
             (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:

               -  Non-selective ß-blockers (topical cardio-selective beta-blocker eye medications
                  for non-narrow angle glaucoma are allowed),

               -  Oral or other systemic corticosteroids,

               -  Oral beta-agonists,

               -  Changes in allergen desensitisation therapy in last 6 months,

               -  Immune system modulating agents such as methotrexate or cyclosporine,

               -  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, chromones or theophylline
             within two weeks prior to Visit 1.

         21. Patients who have been treated with tiotropium within 3 weeks prior to Visit 1.