Efficacy and Safety of 4 Weeks Treatment With Inhaled BI 1744 CL in Japanese Patients With COPD

Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL Delivered by the Respimat Inhaler in Japanese Patients With COPD

The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL inhalation solution delivered by the Respimat inhaler once daily for 4 weeks in Japanese patients with chronic obstructive pulmonary disease (COPD). The selection of the optimum dose(s) will be based on bronchodilator efficacy, safety evaluations and pharmacokinetic evaluations.

Inclusion Criteria:

1. All patients must sign an informed consent consistent with GCP guidelines prior to participation in the trial.
2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: Patients must have relatively stable, moderate to severe airway obstruction with a post-bronchodilator FEV1 >=30% of predicted normal and <80% of predicted normal and a post-bronchodilator FEV1/FVC <70% at Visit 1
3. Male or female patients, 40 years of age or older
4. Patients must be current or ex-smokers with a smoking history of more than 10 pack-years. Pack-Years = [Number of cigarettes/day/20] - years of smoking Patients who have never smoked cigarettes must be excluded.
5. Patients must be able to perform technically acceptable pulmonary function tests (both supervised and unsupervised) and PEFR measurements, and must be able to record a patient diary during the study period as required in the protocol.
6. Patients must be able to inhale medication in a competent manner from the Respimat inhaler and from a MDI.

Exclusion Criteria:

1. Patients with a significant disease other than COPD; 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 with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an AST >80 IU/L, ALT >80 IU/L, bilirubin >1.5 x ULN or creatinine >1.5 x ULN will be excluded regardless of clinical condition (a repeat laboratory evaluation will not be conducted in these patients)

3. Patients with a history of asthma or a total blood eosinophil count >=600/mm3. A repeat eosinophil count will not be conducted in these patients

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 (e.g. repeated demonstration of a QTc interval >450 ms) as recommended by ICH E14. For patients who have a QTc interval between 450 ms and 500 ms, as judged by site personnel, there will be a confirmatory reading by centralized evaluation institute. If the confirmatory reading is still greater than 450 ms, patient will be excluded. Patients with a QTc interval >=500 ms will immediately be excluded from the study.
   • 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
   • a diagnosis of clinically relevant cardiac arrhythmia
   • known active tuberculosis
   • a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last 5 years (patients with treated basal cell carcinoma are allowed)
   • a history of life-threatening pulmonary obstruction
   • a history of cystic fibrosis
   • clinically evident bronchiectasis
   • a history of significant alcohol or drug abuse

6. Patients who have undergone thoracotomy with pulmonary resection (patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1)

7. Patients being treated with any of the following concomitant medications:

   • medications that prolong the QT/QTc interval
   • oral beta-adrenergics and beta-adrenergics patchs
   • beta-blockers (topical beta-blockers for ocular conditions are allowed)
   • oral corticosteroid medication at unstable doses (i.e. less than 6 weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.

8. Patients who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits

9. Patients who have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program

10. Patients who have taken an investigational drug within 1 month or 6 half lives (whichever is greater) prior to screening visit

11. Patients with known hypersensitivity to beta-adrenergics drugs, BAC, EDTA or any other component of the Respimat inhalation solution delivery system

12. Pregnant or suspect of pregnant or women who are willing to become pregnant during the study period or nursing women

13. Patients who have previously been participated in this study or are currently participating in another study

14. Patients who are unable to comply with pulmonary medication restrictions prior to randomisation

15. The randomization of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the screening visit or during the screening period should be postponed. Patients may be randomised 6 weeks following recovery from the infection or exacerbation