Inclusion Criteria:

• Male or female between 40 and 75 years of age

• A female subject is eligible to participate if she is of:

  • Non childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy, bilateral salpingectomy or bilateral oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 40 pg/ml (<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
• Male subjects must agree to use one of the listed contraception methods. This criterion must be followed from the time of the first dose of study medication until 90 days post-last dose.
• Subject diagnosed with COPD, as defined by the GOLD guidelines.
• BMI within the range 18 - 34 kg/m2 (inclusive).
• Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (Pack years = (cigarettes per day smoked/20) x number of years smoked)).
• Average QTcB or QTcF ≤ 450 msec taken from triplicate assessments at screening; or QTc ≤ 480 msec in subjects with Bundle Branch Block.
• Subject has a post-bronchodilator (400 μg salbutamol) FEV1 of ≥ 35% to ≤ 80% of predicted normal.
• Subject has FEV1/FVC < 0.7 post-bronchodilator (400 μg salbutamol).
• Subjects have a 24hour holter recording that is within normal limits for the individual 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.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Subject is available to complete all study measurements and procedures.

Exclusion Criteria:

• Subjects who have a past or present disease, which as judged by the Investigator, may affect subject safety or influence the outcome of the study.
• Subjects with a 2D6 poor metaboliser genotype.
• The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine and opiates.

The detection of drugs taken for a legitimate medical purpose would not necessarily be an exclusion to study participation. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.

• Female subject has a positive pregnancy test.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A positive test for HIV antibody (if tested, according to local SOP's).

• History of high alcohol consumption within 1 month of the study defined as:

  • an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• History of sensitivity to any of the study medications, or components thereof (including allergy to milk protein/lactose) or a history of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation.
• Subject has donated a unit (400 mL) of blood within 60 days of screening or, intends to donate during the study.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• The subject is unable to use the novel dry powder inhaler correctly.
• The subject requires treatment for prostate hypertrophy.
• The subject has a history of narrow angle glaucoma.

Respiratory criteria

• Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the Investigator, compromise the safety of the subject or affect the interpretation of the results.

• Subject has poorly controlled COPD, defined as the occurrence of any of the following:

  • Either: acute worsening of COPD that is managed by the subject at home requiring treatment with corticosteroids in the 2 weeks prior to the screening visit.
  • Or: more than two exacerbations in the previous 4 months prior to the screening visit that required a course of oral corticosteroids or, for which the subject was hospitalised.
• Subject has had a respiratory tract infection in the 2 weeks prior to first dose.

Cardiovascular criteria

• Current congestive heart failure (greater than NYHA II) and myocardial infarction (within 9 months of the screening date).
• A history of clinically significant arrhythmia or clinically important 24 h 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, or an ECG that is not suitable for QT measurements (e.g. LBBB or poorly defined termination of the T wave).
• Third degree heart block or pacemaker.
• Risk factors for torsades des pointes (heart failure NYHA II-IV, familial long QT syndrome).
• Elevated resting blood pressure or a mean blood pressure equal to or higher than 150/90 mmHg at screening. A history of and treatment for hypertension is acceptable provided control has been achieved for > 2 months prior to screening.
• A mean heart rate outside the range 50-100 bpm at screening.

Concurrent medication criteria

• Subject requires treatment with nebulised beta-2 agonist or nebulised anticholinergics.
• Subject has received oral or parenteral corticosteroids within 2 weeks of screening.
• Subject is unable to abstain from long-acting bronchodilators from 48 hours prior to the screening and treatment periods (i.e. the last assessment in the dosing period).

(Note, subjects may resume use of their usual medication in between screening and the treatment period if the restrictions in Section 9 Concomitant Medications and Non-Drug Therapies are followed and provided the long acting bronchodilator component is stopped again 48h or more prior to dosing).

• Subject is receiving co-medication with drugs which are commonly recognised to prolong the QTc interval (e.g. quinolones, amiodorane, disopyramide, quinidine, sotalol, chlorpromazine, haloperidol, ketoconazole, terfenadine, cisapride and terodiline).
• Subject requires regular treatment with oral corticosteroids (prednisolone or equivalent).
• Subject is receiving treatment with beta-blockers, except eye drops.
• Subject is receiving treatment with long-term or short-term oxygen therapy, NIPPV or requires nocturnal positive pressure for sleep apnea.