Fluticasone Propionate/Salmeterol Combination 250/50 DISKUS in the Exercise Endurance Time in Patients With Chronic Obstructive Pulmonary Disease

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria at V1.

• Consent: A signed and dated written informed consent must be obtained from the subject and/or subject's legally acceptable representative prior to study participation.
• Age: at least 40 yr of age
• Sex: Male or Female

Females are eligible to participate only if they are currently not pregnant and not lactating. In addition, female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A female is otherwise 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,
• child-bearing potential, has a negative pregnancy test (urine) at screening, and is committed to the consistent and correct use of an acceptable method of birth control, starting at V2, 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 at least one of the following:
• use of implants of levonorgestrel or etonogestrel
• percutaneous contraceptive patches
• use of injectable progestogen
• use of oral contraceptive (either combined estrogen/progestin or progestin only)
• use of any intrauterine device (IUD) with published data showing that the highest expected failure rate is less than 1% per yr
• male partner is sterile (vasectomy with documentation of azoospermia; note that a verbal report of azoospermia is acceptable) and is the sole sexual partner for that female subject prior to the female subject's entry into the study
• double-barrier method; condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicide
• abstinence: if not sexually active, must commit to complete abstinence from intercourse

Female subjects, with the exception of those who are post-menopausal or surgically sterile, will undergo urine pregnancy tests approximately 7 days prior to first dose and approximately monthly.

• Diagnosis: An established clinical history of COPD in accordance with the definition of the American Thoracic Society (ATS).
• Severity of Disease: FEV1 post-albuterol/salbutamol at least 30 to no more than 80% of predicted normal and FEV1/FVC ratio post-albuterol/salbutamol of no more than 0.70 based on NHANES III reference values. Note that identical formulations of short-acting beta-agonist are called albuterol in the US and salbutamol in Canada.
• Smoking History: A history of smoking at least 10 pack-yr is required. Pack-yr are defined as the number of packs of cigarettes smoked per day multiplied by the number of yr smoked. Please note that both current and previous smokers are eligible for this study. Previous smoking is defined as no smoking for at least 6 months prior to consent; subjects are otherwise considered "current" smokers.
• CXR: Chest radiograph, within 1 yr prior to consent, without findings suspected to represent an active, clinically-significant process other than those believed to be related to uncomplicated COPD.
• Use of TIO: A history of using TIO with compliance at least 80% starting at least 14 days prior to V1, and ending 24 hr prior to V1, is required. Please note that any subject whose medical history precludes the safe use of TIO (such as significant narrow-angle glaucoma, known urinary retention, etc) should not be started on TIO for the purpose of this study.

Exclusion Criteria

Subjects meeting any of the following criteria at V1 must not be enrolled in the study:

• Asthma: A current diagnosis of asthma.
• Other Diseases/Abnormalities: Any significant disease that, in the opinion of the investigator, would put the safety of the subject at risk through study participation, or which would affect the efficacy analysis if the disease/condition exacerbated during the study. Previously diagnosed cancer is considered a significant disease unless it