Efficacy and Safety of 4 Weeks Treatment With Inhaled BI 1744 CL in Japanese Patients With COPD
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Pulmonary Disease, Chronic Obstructive
Intervention: BI 1744 CL 2 Âµg; BI 1744 CL 5 Âµg; BI 1744 CL 10 Âµg; Placebo
Intervention description: 2 puffs of 1 Âµg/actuation delivered by the RespimatÂ® inhaler; 2 puffs of 2.5 Âµg/actuation delivered by the RespimatÂ® inhaler; 2 puffs of 5 Âµg/actuation delivered by RespimatÂ®; 2 puffs delivered by the RespimatÂ® inhaler
Intervention MeSH terms: Olodaterol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 328.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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