ADOAIR250 Anti-inflammatory Effects in Japanese Subjects With Chronic Obstructive Pulmonary Disease

A 12-week Randomised, Double-blind, Parallel-group Study to Evaluate the Anti-inflammatory Effects of ADOAIR® 50/250mcg Twice Daily Compared With Placebo Twice Daily in Japanese Subjects With Chronic Obstructive Pulmonary Disease (COPD)

The study will be conducted in a respiratory specialist institute in Japan, with standardized techniques and data assurance checks to optimize data quality. The licensed dosage and administration of Adoair in Japan will be applied in this study. Each subject will receive treatment options in a randomized blinded fashion. Subjects will be randomized following a 4-week wash-out phase to take either Adoair 50/250mcg twice daily or placebo twice daily for 12 weeks.

This is a randomised, double-blind, placebo-controlled, two-arm, parallel-group, 12-week-treatment study in Japanese patients with COPD.

At Visit 1, patients confirmed to be fulfilling all the inclusion criteria and not meeting any of the exclusion criteria will start the 4-week run-in period. During the entire study period, including the run-in period, the only drug allowed to use in addition to the study drug will be oxitropium (short-acting anticholinergic drug) as relief medication. At the end of the run-in period (Visit 2), subjects eligible for randomisation will be evenly randomised to one of the following two treatment groups and start the 12-week treatment period.

• ADOAIR®250 one inhalation twice daily from the DISKUS inhaler
• Placebo one inhalation twice daily from the DISKUS inhaler

Study completers will be defined as subjects who have completed all examinations, assessments, and study procedures in the study period, including the run-in period and the follow-up period. At completion/discontinuation of the treatment period, subjects will be switched to appropriate COPD treatment at the discretion of the investigator (or subinvestigator).

Inclusion Criteria:

1. Japanese (male or female) outpatients aged 40-80 years inclusive at Visit 1 (Female patients may be enrolled only if they are not of child-bearing potential, or are of child-bearing potential who agree to properly use protocol-specified contraceptive measures. )
2. Have a diagnosis of COPD (defined as per the COPD guideline)
3. Have a FEV1/FVC ratio < 0.70 at 15-60 minutes following use of SALTANOL® INHALER
4. Have a FEV1 of >= 40% to < 80% of the predicted normal value at 15-60 minutes following use of SALTANOL® INHALER
5. Current or ex-smokers with a smoking history of at least 10 pack-years
6. Able to use the DISKUS inhaler and the short-acting inhaled anticholinergic drug
7. Capable of providing written voluntary consent to participate in the study

Exclusion Criteria:

1. Diagnosed by the investigator (or subinvestigator) as having bronchial asthma
2. Have any respiratory disorder other than COPD (e.g., lung cancer, sarcoidosis, tuberculosis [including old tuberculosis], pulmonary fibrosis)
3. Have a chest X-ray (or CT scan) indicating a diagnosis other than COPD that might interfere with assessments in the study (This must be assessed using last imaging study performed within 6 months prior to Visit 1; or, a chest X-ray must be obtained at Visit 1.)
4. Have chronic respiratory failure
5. Have undergone lung volume reduction and/or lung transplant
6. Have had a COPD exacerbation or respiratory infection requiring systemic corticosteroid or microbial therapy or hospitalisation, within 6 weeks prior to Visit 1
7. Have used inhaled corticosteroids and systemic corticosteroids within 4 weeks prior to Visit 1
8. Have used long-acting β2 agonists (inhaled or patch) within 2 weeks prior to Visit 1
9. Are unable to stop their short-acting β2 agonist therapy at Visit 1 (During the study participation, oxitropium bromide (TERSIGAN) will be used as relief medication.)
10. Receiving long-term oxygen therapy with oxygen use for more than 12 hours per day
11. Have a concurrent serious or uncontrolled disease that might interfere with assessments in the study (including psychiatric disease, unstable liver disease, and heart disease)
12. Have a QTc > 450 msec (or > 480 msec in patients with bundle branch block) at Visit 1 (based on average QTc from three consecutive cardiac cycles on ECG)
13. Have participated in another study and received any other study drug within 4 weeks prior to Visit 1
14. Diagnosed by the investigator (or subinvestigator) as having drug or alcohol dependence
15. Have known or suspected hypersensitivity to bronchodilators, inhaled corticosteroid, or lactose
16. Have known α1 antitrypsin deficiency
17. Previously enrolled in this study
18. Judged by the investigator (or subinvestigator) to be inappropriate to participate in this study