A 4-week Dose-Ranging, Dose-Interval, Efficacy, Safety and Tolerability Study of GSK961081 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

This is a phase IIb multicentre, randomised, double-blind, double-dummy, placebo- and active-controlled, parallel-group, dose-ranging and dose-interval study. Eligible subjects will enter a seven-day run-in period followed by 28 days of double-blind, double-dummy treatment via the DISKUS inhaler. The study will consist of 8 visits, mainly conducted on an outpatient basis, 6 of which will be clinic visits and 2 of which will be phone contacts, including a post-treatment visit to follow up any adverse events. There will be approximately 425 subjects randomised to the study.

Inclusion criteria

• Outpatient Subjects
• Subjects who give their signed and dated informed consent to participate
• 40 or more years of age, inclusive, at Visit 1
• Male or females
• Subjects with an established clinical history of COPD
• Current or previous cigarette smokers with a history of ≥ 10 pack-years of cigarette smoking
• Subjects with the following liver function test values:
• Subjects with a measured post-salbutamol FEV1/FVC ratio of < 0.70 at Visit 1 (Screening).
• Subjects with a measured post-salbutamol FEV1 30-70% of predicted normal values

Exclusion criteria

• Women who are pregnant or lactating or are planning to become pregnant during the study.
• Current diagnosis of asthma
• Other significant respiratory disorders besides COPD, including alpha-1 deficiency
• Previous lung resection surgery
• Significant abnormalities in chest x-ray presentation
• Hospitalization for a COPD exacerbation within 12 weeks prior screening
• Use of oral corticosteroids or antibiotics for COPD or antibiotics for a lower respiratory tract infection within 6 weeks
• Any significant disease that would put subject at risk through study participation
• BMI greater than 35
• Pacemaker
• Significantly abnormal ECG, clinical lab finding (including Hepatitis B or C)
• Cancer
• Allergy or hypersensitivity to beta adrenergic receptor-agonist, sympathomimetic, anticholinergic/anti-muscarinic receptor antagonist, or inhaler excipients
• Diseases that would contra-indicate the use of anticholinergics
• Use of sysemic corticosteroids within 6 weeks of screening
• Use of long-acting beta-agonists within 48 hours of screening
• Use of tiotropium within 7 days of screening
• Use of theophyllines or anti-leukotrienes within 48 hours of screening
• Use of short-acting bronchodilators within 4 hours of screening
• Use of investigational medicines within 30 days of screening
• Use of high dose inhaled corticosteroids
• Use of long-term oxygen therapy, CPAP or NIPPV
• Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1
• Regular (q.i.d or greater) use of short acting bronchodilators, including nebulized therapy
• Affiliation with Investigator Site
• Questionable Validity of Consent
• Previous use of GSK961081