A Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetic (PK), and Pharmacodynamic (PD) Profiles of 3 Doses of Fluticasone Furoate (FF)/GW642444 Inhalation Powder at the End of a 28-day Treatment Period in Subjects With Chronic Obstructive Pulmonary Disease (COPD) Compared to Placebo

Inclusion Criteria

• Outpatient/Inpatient; Male or female subjects
• Subjects must give their signed and dated written informed consent to participate.
• A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic, > 45 years, in the absence of hormone replacement therapy. However in questionable cases, a blood sample with FSH >40MIU/ml and estradiol < 40pg/ml (<140 pmol/L) is confirmatory.

OR

Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study - screening to follow-up contact):

• Complete abstinence from intercourse from screening until the follow-up contact; or
• Male partner is sterile (vasectomy with documentation of azoospermia) prior to female subject entry into the study, and this male partner is the sole partner for that subject; or
• Implants of levonorgestral inserted for at least 1 month prior to the study medication administration but not beyond the third successive year following insertion; or
• Injectable progestogen administered for at least 1 month prior to study medication administration; or
• Oral contraceptive (combined or progestogen only) administered for at least one monthly cycle prior to study medication administration; or
• Double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository); or
• An intrauterine device (IUD), inserted by a qualified physician, with published data showing that the highest expected failure rate is less than 1% per year; or
• Estrogenic vaginal ring; or
• Percutaneous contraceptive patches.
• Age: ≥40 years of age at Screening (Visit 1).
• COPD diagnosis: Subjects with a clinical history of COPD in accordance with the following definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]: COPD is a preventable and treatable disease characterized 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.
• Tobacco use: subjects with a current or prior history of ≥10 pack-years of cigarette smoking at Screening (Visit 1). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Screening (Visit 1).

Note: Pipe and/or cigar use cannot be used to calculate pack year history. Number of pack years = (number of cigarettes per day/20)) x number of years smoked

• Severity of Disease:
• Subject with a measured post-albuterol/salbutamol FEV1/FVC ratio of ≤0.70 at Screening (Visit 1). [Pelligrino, 2005]
• Subjects with a measured post-albuterol/salbutamol FEV1 ≤ 70% of predicted normal values calculated using NHANES III reference equations [Hankinson, 1999] at Screening (Visit 1). Post-bronchodilator spirometry will be performed approximately 10-15 minutes after the subject has self-administered 4 inhalations (i.e. total 400mcg.) of albuterol/salbutamol via an MDI with a valved-holding chamber. The FEV1/FVC ratio and FEV1 percent predicted values will be calculated by the centralized spirometry equipment.
• Dyspnea: Achieved a score of ≥2 on the Modified Medical Research Council Dyspnea Scale (mMRC, 0-4 scale) at Screening (Visit 1).

Exclusion Criteria

• Pregnancy: Women who are pregnant or lactating or are plan