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.
Minimum age: 40 Years.
Maximum age: 85 Years.
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)
- 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,
- 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
- Subject must be able to read, comprehend, and record information in English or
- 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
- 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
- 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
- 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