Inclusion Criteria:

• Subject is male or female (of non-child bearing potential) ≥ 40 years of age and ≤ 75 years of age.
• Non- child bearing potential is defined as physiologically incapable of becoming pregnant, including females who are post-menopausal (more than 2 years without menses with appropriate clinical history i.e. age, history of vasomotor symptoms-estradiol and FSH levels may be checked if indicated) and females who are surgically sterile (hysterectomy, tubal ligation or bilateral oophorectomy).
• Subject diagnosed with COPD in accordance with ATS/ERS guidelines (as per protocol).
• Subject is a smoker or an ex-smoker with a 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)
• Subject has FEV1 < 80 % of predicted normal for height, age, gender after inhalation of salbutamol
• Response to ipatropium bromide defined as:
• Either an increase in FEV1 of > 12 % and > 150 mL within 2 hours following inhalation of 80 µg ipratopium bromide (Atrovent MDI via spacer) at the screening visit
• Or: a documented increase in FEV1 of >12 % and > 150 mL within 2 hours following inhalation of 80 µg ipratopium bromide within 6 months of screening and an increase in FEV1 of > 6 % and > 100 mL within 2h following inhalation of 80 µg ipratopium bromide (Atrovent MDI via spacer) at the screening visit (in order to allow for potential fluctuations in the response to ipratropium bromide in patients known to be responders to ipratropium bromide)
• Response to salbutamol defined as:
• Either an increase in FEV1 of > 12 % and > 150 mL within 2 hours following inhalation of 400 µg salbutamol MDI (via spacer) at the screening visit
• Or: a documented increase in FEV1 of >12 % and > 150 mL within 2 hours following inhalation of 400 µg salbutamol MDI within 6 months of screening and an increase in FEV1 of > 6 % and >100 mL within 2h following inhalation of 400 µg salbutamol MDI (via spacer) at the screening visit (in order to allow for potential fluctuations in the response to salbutamol in patients known to be responders to salbutamol)
• Body mass index (BMI) within the range 18-35 kg/m2
• Subject is able and willing to give written informed consent to take part in the study.
• Subject is available to complete all study assessments

Exclusion Criteria:

• Subjects who have a past or present disease, which as judged by the Investigator and medical monitor may affect the outcome of the study or the safety of the subject
• Subjects with clinically relevant findings on laboratory safety tests. Subjects with laboratory values outside the reference range may be include in the study if the Investigator and medical monitor agree that these findings would not put the subject at risk or interfere with the objectives of the study
• Women who are pregnant or lactating
• An unwillingness of subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or tubal ligation if the woman could become pregnant from the time of the first dose study medication until 90 days post-dose
• The subject has a positive urine drugs of abuse screen. A minimum list of drugs that will be screened for include amphetamines, barbituates, cocaine, opiates, cannabinoids and benzodiazepines.
• A history, or suspected history, of alcohol abuse within the 6 months before the screening visit.
• A positive test for hepatitis C antibody, hepatitis B surface antigen, or HIV.
• The subject has participated in a clinical study with another New Chemical Entity within the past 2 months or participated in a clinical study with any other drug during the previous month.
• The subject has donated a unit of blood within the 56 days of dosing or intends to donate within 56 days after completing the study.
• Subject has an FEV1 < 40 % of predicted for age, height and gender after inhalation of salbutamol.
• The subject has a diagnosis of active tuberculosis, lung cancer, sarcoidosis, bronchiectasis, lung fibrosis, pulmonary hypertension or with a primary diagnosis of asthma
• The subject has a known allergy or hypersensitivity to ipratropium bromide, salbutamol, or lactose
• A subject in whom ipratropium bromide or salbutamol is contraindicated
• Subjects with lung volume reduction surgery within 12 months of screening
• Poorly controlled COPD defined as:
• Either: acute worsening of COPD that is managed by the subject at home by treatment with increased corticosteroids or antibiotics in the 6 weeks before screening
• Or: more than 2 exacerbations in the previous 12 months before screening that required a course of oral steroids or antibiotics, and/or required hospitalisation
• Subject has had a respiratory tract infection in the 4 weeks before screening
• Subject requires treatment with inhaled cromolyn sodium, theophyline, oral ß2- agonists, nebulised anticholinergics or leukotriene antagonists
• Subject is unable to abstain from long acting ß2-agonist from 72 hours before screening and throughout the dosing period
• Subject is unable to abstain from tiotropium bromide from 28 days before screening and throughout the dosing period
• Subject is predicted to be unable to abstain from short acting inhaled ß2-agonists or short acting antimuscarinics for 6 hours before screening and for 6 hours before dosing with GSK961081 until all post-dose lung function tests have been completed for a given study day.
• Subject has received oral corticosteroids within the 6 weeks before screening
• Subject is receiving > 1000 µg FP (or equivalent) a day of inhaled corticosteroid or has changed dose within the 6 weeks before screening or is predicted not to be able to maintain a constant dose during the study
• Subject is receiving oxygen therapy or nocturnal positive pressure treatment
• Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator would prevent use of an inhaled anticholinergic
• The subject is unable to use the dosing devices (MDPI/ MDI/ spacer) correctly.
• Subject with carcinoma that has not been in complete remission for at least 5 years (with the exception of carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma if the subject is considered cured)
• A history of congestive heart failure, coronary insufficiency or cardiac arrhythmia or a finding on screening 24h Holter monitor that would contraindicate the subject's participation in the study
• 12- lead ECG abnormality which is either clinically significant or may interfere with QTc measurement or QTc > 450 msec or PR interval outside the range 120 to 220 msec.
• A supine mean heart rate outside the range 40-90 bpm at screening.
• Persistently elevated supine blood pressure higher than 160/95 at screening.
• Subject is receiving a high-dose diuretic and/ or ß2-adrenergic antagonist
• Subject has a serum potassium level below the reference range at screening.
• Inability to understand the protocol requirements, instructions and study-related restrictions; the nature, scope and possible consequences of the study.
• Unlikely to complete the study; e.g., uncooperative attitude, inability to return for follow-up visits.