A Study of the Safety and Efficacy of 4 Doses of BI 1744 CL Delivered Via the Respimat in Patients With Asthma.

A Randomised, Double-Blind, Placebo- and Active-Controlled, Incomplete Crossover Efficacy and Safety Comparison of 4-week Treatment Periods of Once Daily Treatment of 4 Doses of BI 1744 CL Inhalation Solution Delivered by the Respimat® in Patients With Asthma

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.

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