A Study To Assess Single Dosage Strength Of GW685698/GW642444 Chronic Obstructive Pulmonary Disease (COPD)

Inclusion Criteria

Subjects eligible for enrollment in the study must meet all of the following criteria:

• Informed consent: Subjects must give their signed written informed consent to participate.
• Gender: Male subjects or female subjects of non-child bearing potential (e.g. post-menopausal or surgical sterile) 40 - 80 years of age at screening (Visit 1).
• Post-menopausal females are defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However if indicated this can be confirmed by estradiol and FSH levels consistent with menopause (according to laboratory ranges) at screening (Visit 1).
• Surgically sterile females are defined as those with a documented (medical report verification) hysterectomy and/or bilateral oophorectomy or Tubal Ligation.
• Furthermore, male subjects in this study must use double-barrier (condom/spermicide) birth control methods or abstain from sexual intercourse with female partners who are pregnant, lactating, or able to bear children in addition to any birth control methods the female partner is using, from the first dose of the study medication until 90 days after the last dose of the study medication.
• 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 previous history of ≥ 10 pack-years of cigarette smoking at screening (Visit 1). Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.
• Number of pack years = (number of cigarette per day/20)) x number of years smoked
• Severity of Disease: subjects who conform to the current severity classification for Stage II/III disease in terms of post-bronchodilator spirometry at Screening Visit 1:
• Subject with a measured post-salbutamol FEV1/FVC ratio of ≤0.70
• Subjects with a measured post-salbutamol FEV1 ≥ 40 % and ≤ 80 % of predicted normal values calculated using NHANES III reference equations.

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:

• Pregnancy: Women who are pregnant or lactating
• Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if COPD is the current diagnosis)
• α1- antitrypsin deficiency: Subjects with α-1 antitrypsin deficiency as the underlying cause of COPD
• Other respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases
• Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening
• Chest X-ray (or CT scan): Subjects with a chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at Screening if a chest X-ray or CT scan is not available within 6 months prior to Screening
• Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of any of the following in the 6 weeks prior to Screening:
• Acute worsening of COPD that is managed by subject with corticosteroids or antibiotics, or
• Acute worsening of COPD that requires treatment prescribed by a physician Subjects who are hospitalized due to poorly controlled COPD within 12 weeks of the Screening Visit
• Lower respiratory tract infection: Subjects with lowe