Evaluate the Efficacy and Safety of GSK573719 Delivered Via a Novel Dry Powder Inhaler in Subjects With COPD

Inhaled bronchodilators, such as beta 2 agonists and anticholinergics, and inhaled
corticosteroids are the mainstays of therapy in patients diagnosed with COPD. Anticholinergic
bronchodilators or long acting muscarinic receptor antagonists function by blocking
endogenous airway smooth muscle cholinergic tone. Treatment with anticholinergics has been
shown to significantly improve forced expiratory volume in 1 second (FEV1), resting and
dynamic lung hyperinflation, symptoms, and exercise capacity in patients with COPD. Currently
tiotropium is the only approved long acting muscarinic antagonist available for treatment of
COPD.This is a multicenter, randomized, double-blind, placebo-controlled, parallel group
study to evaluate the efficacy and safety of GSK573719 Inhalation Powder of 2 doses when
administered once-daily via Novel DPI compared with placebo over a treatment period of 12
weeks in subjects with COPD. There will be a total of 8 study clinic visits conducted on an
outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will
complete a 5 to 9 days run-in period followed by a 12-week treatment period. There will be 8
clinic visits during three of which serial spirometry will be performed . The total duration
of subject participation in the study will be approximately 14 weeks.

This is a Phase III multicenter, randomized, double-blind, placebo-controlled, parallel group
study to evaluate the efficacy and safety of GSK573719 Inhalation Powder 62.5 mcg and 125 mcg
when administered once-daily via Novel DPI compared with placebo over a treatment period of
12 weeks in subjects with COPD.

Eligible subjects will be randomized 1:1:1 to receive either of the two doses of GSK573719
Inhalation Powder doses or placebo for 12 weeks.

There will be a total of 8 study clinic visits conducted on an outpatient basis. Subjects who
meet the eligibility criteria at Screening (Visit 1) will complete a 5 to 9 days run-in
period followed by a 12-week treatment period. Clinic visits will be at Screening,
Randomization (Visit 2), Day 3 and Weeks 2, 4, 8, and 12, and 1 day after the Week 12 visit
(Visits 1 to 8, respectively). A safety follow-up assessment will be conducted by telephone
approximately 7 days after the end of the study treatment (FU Phone Contact). The total
duration of subject participation, including the follow-up period will be approximately 14
weeks. All subjects will be provided with albuterol/salbutamol for use on an "as-needed"
basis throughout the run-in and treatment periods.

Pre-dose spirometry will be conducted at each clinic visit. Six hour post-dose serial
spirometry will be conducted at Visit 2 and at Visits 5 and 7. All subjects will be provided
with a paper diary for completion everyday throughout the run-in period and 12-week treatment
period. Subjects will use the diary to record their daily use of supplemental
albuterol/salbutamol and to record any medical problems experienced and any medications used.

At Visit 2 the Baseline Dyspnea Index (BDI) will be administered. The Transition Dyspnea
Index (TDI) will be administered at Visits 5, 6, and 7.

Disease specific health status will be evaluated using the St. George's Respiratory
Questionnaire (SGRQ) at Visit 2 and Visits 5, 6 and 7. Vital signs (blood pressure and pulse
rate), 12-lead ECGs and standard clinical laboratory tests (hematology and blood
biochemistry) including pharmacokinetic samples will be obtained at selected clinic visits.

Approximately 198 subjects will be randomized to ensure at least 168 subjects complete the
treatment period.

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
adequately controlled

- Significant allergy or hypersensitivity to anticholinergics, beta2-agonists, 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, high
dose inhaled steroids (>1000mcg fluticasone propionate or equivalent), PDE4
inhibitors, tiotropium, oral beta2-agoinists, short- and long-acting inhaled
beta2-agonists, 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 the combination of GSK573719/GW642444