A Study of the Safety and Efficacy of 4 Doses of BI 1744 CL Delivered Via the Respimat in Patients With Asthma.
Condition: Asthma
MeSH terms: Asthma
Intervention: Placebo; Olodaterol (BI 1744) high; Olodaterol (BI 1744) medium; Olodaterol (BI 1744) very low; Formoterol 12 mcg; Olodaterol (BI 1744) low
Intervention description: Determine efficacy and safety of Placebo inhaled once daily from the Respimat inhaler and/or twice daily from the Aerolizer inhaler; Determine efficacy and safety in 4 different doses of Olodaterol (BI 1744) inhaled once daily via the Respimat; Determination of efficacy in 4 different doses of Olodaterol (BI 1744) inhaled once daily via the Respimat; Determination of efficacy in 4 different doses of Olodaterol (BI 1744) inhaled once daily via the Respimat; Determine efficacy and safety of 12 mcg Formoterol dose inhaled orally twice daily from the Aerolizer in comparison to other treatment groups; Determine efficacy and safety of 4 different doses of Olodaterol (BI 1744) inhaled once daily via the Respimat
Intervention MeSH terms: Formoterol Fumarate; Olodaterol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Enrollment: 198.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to determine the efficacy and safety of 4 doses of BI
      1744 CL inhalation solution delivered by the Respimat® inhaler once daily for four weeks in
      patients with asthma in comparison to placebo.
    

Eligibility criteria:

        Inclusion criteria:

          1. All patients must sign an informed consent consistent with International Conference on
             Harmonisation-Good Clinical Practice (ICH-GCP) guidelines prior to participation in
             the trial, i.e. prior to any study procedures which includes medication washout and
             restrictions. A separate informed consent is required for pharmacogenomic sampling.

          2. Male or female patients, aged between 18 and 70 years of age, diurnally active

          3. A history of asthma diagnosed by physician at least 3 months prior to Visit 1 at GINA
             treatment steps 3 or 4. The diagnosis of asthma must have been made before the age of
             40.

          4. Pre-bronchodilator FEV1 between 60% predicted and 90% predicted at Visit 1.

          5. Increase in FEV1 greater or equal to 12% and 200 ml 15 minutes after 400mcg salbutamol
             (albuterol) at Visit 1.

          6. Patient must have been taking inhaled corticosteroids (ICS) for at least 12 weeks
             prior to screening, and must have been receiving at a stable dose for at least 6 weeks
             prior to screening either: - a medium to high dose ICS or - a low to high dose ICS in
             combination with Long acting beta agonist (LABA).

          7. All patients must be symptomatic.

        Exclusion criteria:

          1. Patients with a significant disease other than asthma; a significant disease is
             defined as a disease which, in the opinion of the investigator, may (i) put the
             patient at risk because of participation in the study, (ii) influence the results of
             the study, or (iii) cause concern regarding the patient's ability to participate in
             the study

          2. Patients who have been hospitalised for an asthma exacerbation within 3 months or had
             an admission to an intensive care unit for asthma within 3 years of Visit 1

          3. Patients will be excluded when they have: - an aspartate aminotransferase (AST) >80
             IU/L, alanine aminotransferase (ALT) >80 IU/L, bilirubin >1.5 X upper limit of normal
             (ULN) or creatinine >1.5 X ULN - clinically relevant abnormal baseline haematology,
             blood chemistry, or urinalysis

          4. Patients with any of the following conditions: - a diagnosis of thyrotoxicosis

               -  a diagnosis of paroxysmal tachycardia (>100 beats per minute)

               -  a marked baseline prolongation of QT/QTc interval at Visit 1 (e.g., repeated
                  demonstration of a QTc interval >450 ms) as recommended by ICH E14

               -  a history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart
                  failure, hypokalemia, family history of Long QT Syndrome) as recommended by ICH
                  E14.

          5. Patients with any of the following conditions: - a history of myocardial infarction
             within 1 year of screening visit (Visit 1)

               -  a diagnosis of clinically relevant cardiac arrhythmia

               -  a history of cor pulmonale

               -  known active tuberculosis

               -  a malignancy for which patient has undergone resection, radiation therapy or
                  chemotherapy within last five years (patients with treated basal cell carcinoma
                  are allowed)

               -  a history of life-threatening pulmonary obstruction

               -  a history of chronic obstructive pulmonary disease

               -  history of cystic fibrosis

               -  clinically evident bronchiectasis

               -  a history of significant alcohol or drug abuse