A 24-week Evaluation of GSK573719/Vilanterol (62.5/25mcg) and Components in COPD

This is a 24-week, phase III multicenter, randomized, double-blind, placebo-controlled,
parallel-group study.

Eligible subjects will be randomized to GSK573719/GW642444 125/25mcg, GSK573719 125mcg,
GW642444 25mcg, and placebo treatment groups in a 3:3:3:2 ratio such that of the planned 1463
total number of randomized subjects approximately 399 subjects will be randomized to each
active treatment group and 266 subjects will be randomized to placebo. All treatments will be
administered once-daily in the morning by inhalation using a Novel Dry Powder Inhaler (Novel
DPI).

There will be a total of 9 study clinic visits conducted on an outpatient basis. Subjects who
meet the eligibility criteria at Screening (Visit 1) will complete a 7 to 14 day run-in
period followed by a 24-week treatment period. Clinic visits will be at Screening,
Randomization (Day 1), Day 2, after 4, 8, 12, 16, and 24-weeks of treatment, and 1 day after
the Week 24 Visit (also referred as Treatment Day 169). A follow-up contact for adverse
assessment will be conducted by telephone approximately 7 days after Visit 9 or the Early
Withdrawal Visit. The total duration of subject participation, including follow-up will be
approximately 27 weeks. All subjects will be provided with albuterol/salbutamol for use on an
"as-needed" basis throughout the run-in and study treatment periods.

At screening, pre-bronchodilator spirometry testing will be followed by
post-albuterol/salbutamol spirometry testing. Post-albuterol/salbutamol FEV1 and FEV1/FVC
values will be used to determine subject eligibility. To further characterize bronchodilator
responsiveness, post-ipratropium testing will be conducted following completion of
post-albuterol/salbutamol spirometry.

Spirometry will be conducted at each post-randomization clinic visit. Six hour post-dose
serial spirometry will be conducted at Visits 2, 4, 6, and 8. Trough spirometry will be
obtained 23 and 24 hours after the previous day's dose of blinded study medication at Visits
3 to 9. All subjects will be provided with an electronic diary (eDiary) for completion daily
in the evening throughout the run-in and treatment periods. Subjects will use the eDiary to
record dyspnea scores using the Shortness of Breath with Daily Activities instrument (SOBDA),
daily use of supplemental albuterol/salbutamol as either puffs/day from a metered-dose
inhaler (MDI) and/or nebules used per day, and any healthcare contacts related to COPD.

Additional assessments of dyspnea will be obtained using the Baseline and Transition Dyspnea
Index (BDI/TDI) which is an interviewer based instrument. At Visit 2, the severity of dyspnea
at baseline will be assessed using the BDI. At subsequent visits (Visits 4, 6, and 8) change
from baseline will be assessed using the TDI. Disease specific health status will be
evaluated using the subject-completed St. George's Respiratory Questionnaire (SGRQ). The SGRQ
will be completed at Visits 2, 4, 6, and 8. Administration of the SGRQ and BDI/TDI should be
done prior to spirometry testing.

The occurrence of adverse events will be evaluated throughout the study beginning at Visit 2.
SAEs will be collected over the same time period as for AEs. However, any SAEs assessed as
related to study participation (e.g., study treatment, protocol-mandated procedures, invasive
tests, or change in existing therapy) or related to a GSK concomitant medication, will be
recorded from the time a subject consents to participate in the study up to and including any
follow up contact.

Additional safety assessments of vital signs (blood pressure and pulse rate), 12-lead ECGs
and standard clinical laboratory tests (hematology and chemistry) will be obtained at
selected clinic visits. Blood samples for population pharmacokinetic analyses will be
obtained.

At selected study sites, a subset of approximately 198 subjects will perform 24-hour serial
spirometry during the study for evaluation of lung function over the dosing period. In
conjunction with the serial spirometry, this subset of subjects will also perform 24 hour
Holter monitoring and provide blood samples for PK analysis.

Inclusion Criteria:

- Diagnosis of COPD

- 10 pack-year or greater history of cigarette smoking

- Post-bronchodilator FEV1/FVC of <0.7

- Predicted FEV1 of 70% of normal or less

- Modified Medical Research Council (mMRC) dyspnea score of 2 or greater

Exclusion Criteria:

- Women who are pregnant, lactating, or planning to become pregnant

- Respiratory disorders other than COPD, including a current diagnosis of asthma

- Clinically significant non-respiratory diseases or abnormalities that are not adequate
controlled

- Significant allergy or hypersensitivity to anticholinergics, beta-agonist, or the
excipients of magnesium stereate or lactose used in the inhaler delivery device

- Hospitalization for COPD or pneumonia within 12 weeks prior to screening

- Lung volume reduction surgery within 12 weeks prior to screening

- Abnormal and clinically significant ECG findings at screening

- Clinically significant laboratory findings at screening

- Use of systemic corticosteroids, antibiotics for respiratory tract infections, strong
cytochrome P450 3A4 inhibitors, high dose inhaled steroids (>1000mcg fluticasone
propionate or equivalent), PDE4 inhibitors, tiotropium, oral beta2-agoinists, short-
and long-acting inhaled beta2-agonists, ipratropium, inhaled sodium cromoglycate or
nedocromil sodium, or investigational medicines for defined time periods prior to the
screening visit

- Use of long-term oxygen therapy (12 hours or greater per day)

- Regular use of nebulized treatment with short-acting bronchodilators

- Participation in the acute phase of a pulmonary rehabilitation program

- A know or suspected history of alcohol or drug abuse

- Affiliation with the investigational site

- Previous use of GSK573719 or GW642444 alone or in combination, including the
combination of fluticasone furoate and GW64244