A 3 Way Cross-over Study Evaluating the Effects of ADOAIR Twice Daily Plus Tiotropium Bromide Once Daily Compared With the Individual Treatments of Japanese Subjects

Inclusion criteria

• Male or female aged 40 - 80 years inclusive
• Has an established clinical history of COPD (defined as per the GOLD definition)
• A signed and dated written informed consent is obtained from the subject prior to study participation
• The subject has a post-bronchodilator FEV1 of >=30% to =<75% of predicted normal at Visit 1
• The subject has a post-bronchodilator FEV1/ FVC ratio <70% at Visit 1
• The subject achieves a score of 1 on the Modified Medical Research Council (mMRC) Dyspnoea Scale at Visit 1
• The subject is a current or ex-smoker with a smoking history of > 10 pack-years (10 pack years is defined as 20 cigarettes per day for 10 years, or 10 cigarettes (or equivalent if subject smoked cigars or a pipe) per day for 20 years). Ex-smokers are required to have stopped smoking for at least 6 months prior to visit 1. Ex-smokers who stopped smoking less than 6 months ago will be defined as current smokers.
• QTc <450 msec at Visit 1; or for patients with Bundle Branch Block QTc should be <480 msec.

(QTc(F) <450msec, or <480 in subjects with right bundle branch block, should be confirmed by the mean of three readings or one reading)

• ALT < 2xULN and bilirubin/ALP < 1.5xULN (>35% direct bilirubin)
• A female is eligible to enter this study if she is: i)of non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal), ii)of child-bearing potential, but has a negative urinary pregnancy test at screening and agrees to take contraceptive precautions (including abstinence) which are adequate to prevent pregnancy during the study or iii)not a nursing mother

Exclusion criteria

• Has had a COPD exacerbation within the 4 weeks prior to Visit 1
• Had any changes in COPD medication in the 4 weeks prior to Visit 1
• Has plan to change the dosage of Xanthines or to stop receiving it during the study
• Has a current medical diagnosis of asthma
• Has a medical diagnosis of narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction that in the opinion of the investigator should prevent them from entering the study Note: As with other anticholinergic drugs, subjects with narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction should only be entered into the study at the Investigator's discretion
• Has known respiratory disorders other than COPD (e.g. lung cancer, sarcoidosis, tuberculosis or lung fibrosis)
• Has undergone lung surgery e.g., lung transplant and/or lung volume reduction
• Is currently receiving pulmonary rehabilitation
• Had a chest X-ray indicating diagnosis other than COPD that might interfere with the study (chest X-ray to be taken at entry, if subject has not had one or CT image taken within 3 months of Visit 1)
• Requires regular (daily) or long term oxygen therapy (LTOT). (LTOT is defined as . 12 hours oxygen use per day)
• Requires regular treatment with oral, parenteral, or depot corticosteroids or has received 2 or more periods of oral corticosteroids for COPD exacerbation in the last 6 months
• Received oral, parenteral, or depot corticosteroids in the 4 weeks prior to Visit 1
• Received antibiotic therapy for either a lower respiratory tract infection or for COPD exacerbation within the 4 weeks prior to Visit 1
• Has been hospitalized for a COPD exacerbation in the last year
• Receiving non-selective β-blockers (except eye drops)
• Has serious, uncontrolled disease likely to interfere with the study (e.g. Left Ventricular failure, anaemia, renal or hepatic disease or serious psychological disorders)
• Received any other investigational drugs within 4 weeks (or 5 half lives) prior to Visit 1
• Has, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse
• Has a known or suspected hypersensitivity to β2-agonists, inhaled steroids, anticholinergic treatments or any components of the formulations (e.g. lactose or milk protein)
• Has previously been enrolled and randomized to this study
• Are not considered able to tolerate three 2-weeks wash-out periods according to the study schedule with all COPD medications removed apart from rescue use of SALBUTAMOL via MDI (inhaled PRN use).
• Is not eligible to participate this study in the opinion of the investigator/subinvestigator.