Safety Study Using GSK233705 And Tiotropium In Patients With Chronic Obstructive Pulmonary Disease

Inclusion criteria

• Of non-childbearing potential.
• Diagnosed with COPD, as defined by the GOLD guidelines.
• Smoker or an ex-smoker with a smoking history of at least 10 pack years.
• FEV1/FVC < 0.7 post-bronchodilator (salbutamol).
• FEV1 <= 80% of predicted normal for height, age and gender after inhalation of salbutamol.
• Response to ipratropium bromide 9.
• Subject's weight is 60kg.

Exclusion criteria

• Past or present disease, which as judged by the Investigator and the Medical Monitor, may affect the outcome of this study.
• FEV1 <=50% of predicted after inhalation of salbutamol.
• Tested positive for hepatitis C antibody, hepatitis B surface antigen or HIV.
• Has claustrophobia that may be aggravated by entering the plethysmography cabinet.
• Has prostate hypertrophy or narrow angle glaucoma.
• Diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, allergic rhinitis, or asthma.
• Poorly controlled COPD.
• Participated in a Pulmonary Rehabilitation Program within 4 weeks prior to screening visit or will enter a program during the study.
• Had a respiratory tract infection in the 4 weeks prior to the screening visit and throughout the duration of the study.
• History of congestive heart failure, coronary insufficiency or cardiac arrhythmia.
• A mean QTc(B) value at screening >440msec, the QTc(B) of all 3 screening ECGs are not within 10% of the mean, a PR interval outside the range 120-210msec or an ECG that is not suitable for QT measurements.
• A history of elevated supine blood pressure or a mean blood pressure equal to or higher than 160/95 mmHg.
• A mean heart rate outside the range 40-90 bpm.
• QTc prolongation >470msec or risk factors for torsades de pointes (heart failure NYHA II-IV, hypokalaemia, familial long QT syndrome).
• Receiving co-medication with drugs which prolong the QTc interval.
• Requires treatment with inhaled cromolyn sodium or nedocromil, oral beta-2-agonists, nebulised beta-2-agonists, nebulised anticholinergics or leukotriene modifiers.
• Unable to abstain from xanthines (other than caffeine.
• Unable to abstain from short-acting inhaled bronchodilators.
• Unable to abstain from long-acting inhaled bronchodilators.
• Changed dose of inhaled or oral corticosteroids within the last 6 weeks.
• Taking more than 10mg/day of prednisolone (or equivalent).
• Receiving treatment with long term or short-term oxygen therapy or requires nocturnal positive pressure for sleep apnea.