Inclusion Criteria:

• Caucasian male or female subjects aged 40-75 years inclusive. The need to recruit only Caucasian subjects is related to the need to rigorously exclude 2D6 poor metabolisers based on genotype.
• Female subjects must be of non-childbearing potential.
• An established clinical history of COPD (ATS/ERS definition).
• 'Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.'
• Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent).
• Subject has FEV1/FVC < 0.7 post-bronchodilator (salbutamol) dose.
• Subject has 40 ≥ FEV1 ≤ 80% of predicted normal for height, age and gender after inhalation of salbutamol dose.
• Response to ipratropium bromide.
• Subject is able and has given written informed consent to take part in the study.
• Subject is available to complete all study measurements and procedures.
• Subject's BMI is 18.0 - 32.0 kg/m2.
• Subjects have a 24hr Holter recording that is within normal limits and does not demonstrate any clinically important abnormality that, in the opinion of the investigator, would make the subject unsuitable for participation in the study

Exclusion Criteria:

• Subjects who have a past or present disease of any organ system, which as judged by the Investigator, may affect the outcome of this study.
• The subject has a positive pre-study drug screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cannabis, Cocaine and Opiates. The detection of drugs with a legitimate medical use would not be an exclusion to study participation.
• The subject has a positive pre-study alcohol screen. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
• A suspected history of alcohol abuse within the six months previous to the screening visit.
• The subject has tested positive for hepatitis C antibody, hepatitis B surface antigen or HIV (if determined by local SOP's).
• Subject has received an investigational drug within 30 days of screening.
• The subject is currently taking medication which is known to be a CYP 2D6 inhibitor/substrate.
• The subject has donated a unit (400ml) of blood within 60 days of screening, or, intends to donate during the study.
• The subject has a known allergy or hypersensitivity to ipratropium bromide, tiotropium bromide, atropine and any of its derivatives or lactose/milk protein.
• Subject is unable to use the DISKUS™/HandiHaler devices correctly.
• Subject has prostatic hypertrophy, bladder outlet obstruction, or narrow angle glaucoma.
• Subjects with a 2D6 poor metaboliser genotype (Caucasian).
• The subject has claustrophobia that may be aggravated by entering the plethysmography cabinet (American Association of Respiratory Care 2001 guidelines for body plethysmography)
• Received antibiotic therapy for either a lower respiratory tract infection or for COPD exacerbation within the 4 weeks prior to Screening.

Respiratory criteria

• Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, allergic rhinitis, or asthma.
• Subject has poorly controlled COPD, defined as either: acute worsening of COPD that is managed by the subject at home by treatment with corticosteroids in the 6 weeks prior to screening visit Or more than two exacerbations in the previous 6 months prior to screening that required a course of oral corticosteroids or antibiotics, or, for which the subject was hospitalised.
• Subject has participated in a Pulmonary Rehabilitation Program within 4 weeks prior to screening visit or will enter a program during the study.
• Subject has had a respiratory tract infection in the 4 weeks prior to the screening visit.

Cardiovascular criteria

• Current congestive heart failure (greater than NYHA I), myocardial infarction (within 3-years of the screening date) or ischaemic heart disease requiring regular therapy (such as β blockers, long-acting nitrates, calcium antagonists or nicorandil). Aspirin, Clopidogrel and statins are allowed.
• A history of clinically significant arrhythmia or clinically important 24hr Holter findings that, in the opinion of the investigator, would cause a safety concern for entry into the study.
• A mean QTc(B) value at screening >450msec, the QTc(B) of all 3 screening ECGs are not within 10% of the mean, or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave)
• Mobitz type II or third degree heart block.
• Risk factors for torsades de pointes (heart failure NYHA II-IV, chronic hypokalaemia, familial long QT syndrome).
• Elevated resting blood pressure or a mean blood pressure equal to or higher than 150/95 mmHg at screening. A history of hypertension is acceptable provided control has been achieved for > 3 months prior to screening with diuretic only.
• A mean heart rate outside the range 50-100 bpm at screening (from vital signs measurement).

Concurrent medication criteria

• Subject requires treatment with inhaled cromolyn sodium or nedocromil, oral β2-agonists, nebulised β2-agonists, nebulised anticholinergics or leukotriene modifiers.
• Subject is unable to abstain from xanthines (other than caffeine) 13-15 days prior to the first dose of study medication until completion of the study (last study-related procedure at the follow-up visit).
• Subject is unable to abstain from short-acting inhaled bronchodilators from 6hrs prior to screening until after completion of screening, or, from 6hrs prior to the administration of study medication until after completion of any given treatment period (i.e. the last assessment in a dosing period).
• Subject is unable to abstain from long-acting inhaled bronchodilators from 72hrs prior to the screening until after completion of all treatment periods (i.e. the last assessment in the final dosing period).
• Subject has changed dose of inhaled corticosteroids within the last 4 weeks, or, will be unable to maintain a constant dose of inhaled corticosteroids during the study.
• Subject is receiving treatment with long term or short-term oxygen therapy or requires nocturnal positive pressure ventilation (CPAP or NIPPV).
• Subject is receiving treatment with beta-blockers, except eye drops, Diltiazem or Verapamil.
• Subject is receiving co-medication with drugs which are commonly recognised to prolong the QTc interval (e.g. quinolones, amiodarone, disopyramide, quinidine, sotalol, chlorpromazine, haloperidol, ketoconazole, terfenadine, cisapride and terodiline).