A 6-month Study to Evaluate the Efficacy and Safety of Fluticasone Furoate (FF)/GW642444 Inhalation Powder in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

A 24-Week Study to Evaluate the Efficacy and Safety of Fluticasone Furoate (FF)/GW642444 Inhalation Powder and the Individual Components Delivered Once Daily (AM) Via a Novel Dry Powder Inhaler Compared With Placebo in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

The Purpose of this study is to assess the efficacy and safety of two strengths of the FF/GW642444 Inhalation Powder in subjects with chronic obstructive pulmonary disease (COPD)

Inclusion Criteria:

• Type of subject: outpatient
• Informed consent: Subjects must give their signed and dated written informed consent to participate.
• Gender: Male or female subjects A female is eligible to enter and participate in the study if she is of:
• Non-child bearing potential OR
• Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods defined in the protocol
• Age: ≥40 years of age at Screening (Visit 1)
• COPD diagnosis: Subjects with a clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]
• Tobacco use: Subjects with a current or prior history of ≥10 pack-years of cigarette smoking at Screening (Visit 1).
• Severity of Disease: Subjects with a Screening (Visit 1) measured post-albuterol/salbutamol:
• FEV1/FVC ratio of ≤0.70 and
• FEV1 ≤70% of predicted normal values
• Dyspnea: Achieved a score of ≥2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Screening (Visit 1).

Exclusion Criteria:

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

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• Asthma: Subjects with a current diagnosis of asthma
• α1-antitrypsin deficiency: Subjects with α1-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 (Visit 1)
• 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.
• Hospitalization: Subjects who are hospitalized due to poorly controlled COPD within 12 weeks of Visit 1.
• Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of the following in the 6 weeks prior to Visit 1: Acute worsening of COPD that is managed by subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician.
• Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1.
• Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular (i.e., pacemaker), neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled.
• Peptic Ulcer disease: Subjects with clinically significant peptic ulcer disease that is uncontrolled.
• Hypertension: Subjects with clinically significant hypertension that is uncontrolled.
• Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded if the subject has been considered cured within 5 years since diagnosis.
• Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medication or components of the inhalation powder
• Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years
• Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol/salbutamol and/or their ipratropium 4 hours prior to spirometry testing at each study visit
• Additional medication: Use of certain medications such as bronchodilators and corticosteroids for the protocol-specified times prior to Visit 1 (the Investigator will discuss the specific medications)
• Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use (i.e., ≤12 hours per day) is not exclusionary.
• Sleep apnea: Subjects with clinically significant sleep apnea who require use of continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV) device.
• Pulmonary rehabilitation: Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening (Visit 1) or who will enter the acute phase of a Pulmonary Rehabilitation Program during the study.
• Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
• Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.
• Prior use of study medication/other investigational drugs
• Affiliation with investigator site: Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study.