An Investigation Of The Interaction Of GSK961081 With Inhaled Beta-Agonist And Anti-Muscarinic Drugs.

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 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 1000 µg FP (or equivalent) a day of inhaled corticosteroid or has changed dose within the 6 weeks before screening or