Chronic Obstructive Pulmonary Disease (COPD) Post-hospitalization Study
Chronic Obstructive Pulmonary Disease (COPD) Post-hospitalization Study
This trial is a randomized, double-blind, parallel-group, multicenter study to be conducted
 in the United States. The purpose of the study is to evaluate the rate of exacerbations of
 chronic obstructive pulmonary disease (COPD) following hospital discharge for an acute
 exacerbation of COPD, in patients receiving either fluticasone propionate/salmeterol
 combination product 250/50mcg BID or salmeterol 50mcg BID via DISKUS™ over 29 weeks. The
 study population will include patients hospitalized for an acute exacerbation of COPD. The
 target enrolment is 720 subjects at 80 study centers. The primary endpoint is the rate of
 exacerbation requiring hospitalization that occur more than 21 days post-discharge, emergency
 room visit or physician's office visit for an exacerbation of COPD requiring treatment with
 oral corticosteroids or oral corticosteroids and antibiotics. The secondary endpoint is the
 rate of COPD exacerbation requiring treatment with oral corticosteroids, antibiotics, and/or
 hospitalization (alone and in combination). Related efficacy endpoints include, time to first
 exacerbation of COPD requiring treatment with oral corticosteroids, antibiotics, and/or
 hospitalization (alone and in combination), pre-dose AM FEV1, the probability of premature
 withdrawal of subject from the study, and supplemental albuterol use, change in biomarkers of
 inflammation, including, surfactant protein D (SP-D), clara cell secretory protein 16 (CC-16)
 and high sensitivity C-reactive protein (hs-CRP). Health outcome assessments include domain
 scores evaluation for fatigue, dyspnea, emotional function and mastery, measured with the
 Chronic Respiratory Disease Questionnaire self-administered standardized format (CRQ-SAS);
 and symptoms (congestion, cough, phlegm, mucus, chest discomfort, shortness of breath and
 sleep disturbance), assessed by the EXAcerbations of Chronic pulmonary disease Tool (EXACT).
 Albuterol will be supplied to study subjects for use as-needed throughout the study. Safety
 will be assessed by monitoring of adverse events.
Inclusion Criteria:

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

 -  Male or female of at least 40 years of age at screening.

 To be eligible for entry into the study, females of childbearing potential must commit to
 the consistent and correct use of an acceptable method of birth control starting on the day
 of visit 1, throughout the clinical trial, and for a period after the trial to account for
 elimination of the drug (minimum of six days), as defined by any one of the following:

 -  Abstinence Females of childbearing potential who are not sexually active must commit
 to complete abstinence from intercourse

 -  Oral contraceptive (either combined estrogen/progestin or progestin only)

 -  Injectable progestogen

 -  Implants of levonorgestrel or etonogestrel

 -  Percutaneous contraceptive patches

 -  Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate
 of less than 1% per year,

 -  Male partner who is sterile (vasectomy with documentation of azoospermia) prior to the
 female subject's entry into the study and is the sole sexual partner for that female
 subject, or

 -  Double-barrier method; condom or occlusive cap (diaphragm or cervical /vault caps)
 plus spermicide.

 -  Current or former smokers with a >10 pack-year cigarette smoking history [number of
 pack years = (number of cigarettes per day / 20) X number of years smoked (e.g., 10
 pack-years is equal to 20 cigarettes per day for 10 years, or 10 cigarettes per day
 for 20 years]. Former smokers are defined as those who have quit smoking for at least
 3 months prior to the screening visit.

 -  Any of the following populations:

 -  Patients hospitalized for a duration not exceeding 10 days due to an acute
 exacerbation of COPD, and who must be randomized within 10 days post-discharge.

 -  Patients with COPD who were treated and held for observation in the emergency
 department (i.e. emergency room, ER) for at least 24 hours due to an acute
 exacerbation of COPD, and who must be randomized within 10 days post-discharge.

 -  Patients who received oral corticosteroids or oral corticosteroids and antibiotics for
 treatment of an exacerbation of COPD during a physician's office visit and who must be
 randomized within 10 days of the visit, and who have been hospitalized within the
 previous six months due to an acute exacerbation of COPD.

 -  Clinical diagnosis of COPD (for at least 6 months). The following definition of COPD
 from the American Thoracic Society (ATS) will be used: COPD is a disease state
 characterized by the presence of airflow obstruction due to chronic bronchitis or
 emphysema; the airflow obstruction is generally progressive, may be accompanied by
 airway hyper-reactivity, and may be partially reversible [American Thoracic Society,
 1995].

 -  Documented evidence (within a year prior to Visit 1) in the medical chart of
 spirometry confirming the diagnosis of COPD and/or spirometry performed prior to
 randomization (Visit 2) that confirms pre-bronchodilator FEV1/FVC ratio less than or
 equal to 0.70 and pre-bronchodilator FEV1 <70% of predicted.

 -  Review and subject's completion of written informed consent: a subject-signed and
 dated written informed consent (form) must be obtained prior to any study procedure,
 and the subject must be willing to comply with all the requirements of the study
 protocol.

 -  Subject must be able to read, comprehend, and record information in English or
 Spanish.

 Exclusion Criteria:

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

 -  Diagnosis of pneumonia, congestive heart failure (CHF), or other complicating
 co-morbid condition while hospitalized within the last 6 months for an exacerbation of
 COPD.

 -  Historical or current evidence of clinically significant uncontrolled disease
 including, but not limited to, those listed below. Significant is defined as any
 disease that, in the opinion of the investigator, would put the safety of the subjects
 at risk through study participation, or which would affect the safety analysis or
 other analyses if the disease/condition exacerbated during the study.

 -  A previous lung resection surgery (e.g. lobectomy, pneumonectomy, etc) within the year
 preceding Visit 1 (Screening)

 -  Asthma as primary diagnosis

 -  Lung cancer

 -  Cystic fibrosis, pulmonary fibrosis, active tuberculosis, or sarcoidosis

 -  Clinically significant cardiac arrhythmias

 -  Uncontrolled hypertension

 -  Unstable angina

 -  Current malignancy or a previous history of cancer in remission for < 5yrs (localized
 basal cell or squamous cell carcinoma of the skin that has been resected is not
 excluded)

 -  Uncontrolled diabetes mellitus

 -  Uncontrolled hyperthyroidism or hypothyroidism

 -  Immunologic compromise

 -  Cushing's or Addison's disease

 -  An abnormal 12-lead electrocardiogram (ECG) at Visit 1 (Screening) deemed to be
 clinically significant by the investigator.

 -  A chest X-ray or computed tomography (CT) scan performed in the 6 months preceding
 Visit 1 that revealed evidence of clinically significant abnormalities not believed to
 be due to the presence of COPD. If the subject does not have a record of a chest
 X-ray, one must be obtained and reviewed prior to randomization.

 -  Female patients with a positive urine pregnancy test at Visit 1.

 -  Any infirmity, physical disability, or geographic location that would limit compliance
 for scheduled visits.

 -  Any adverse reaction, immediate or delayed, hypersensitivity to any Beta-agonist,
 sympathomimetic drug, or corticosteroid including any components of the study drug
 formulations.

 -  Limited ability to provide a valid informed consent due to psychiatric disease,
 intellectual deficiency, poor motivation, current substance abuse (including illicit
 drugs and alcohol), or neurological disorders that might interfere with completion of
 study procedures or hearing problems that may impede effective communication.

 -  Study site staff (i.e. participating investigator, sub-investigator, study
 coordinator, employee of the participating investigator) or family members of site
 staffs.