GSK573719 Dose Ranging Study in Chronic Obstructive Pulmonary Disease

This is multicenter, randomized, double-blind, double-dummy, placebo-controlled, three-way
cross-over, incomplete block design study to evaluation of 5 doses of GSK573719 administered
once-daily and 3 doses of GSK573719 administered twice-daily over 14 days in subjects with
COPD and will include tiotropium as an open-label active control. The pharmacokinetic profile
of GSK573719 will also be evaluated.

Inclusion Criteria:

- A signed and dated written informed consent prior to study participation

- Males or females of non-childbearing potential

- 40 to 80 years of age

- COPD diagnosis

- 10 pack-years history or greater of cigarette smoking

- Post-bronchodilator FEV1/FVC ratio of 0.70 or less

- Post-bronchodilator FEV1 of 35 to 70% of predicted normal

Exclusion Criteria:

- Asthma

- Other significant respiratory disorders besides COPD, including alpha-1 deficiency

- Previous lung resection surgery

- Use of oral steroids or antibiotics for a COPD exacerbation within 6 weeks of
screening

- Hospitalization for COPD or pneumonia within 3 months of screening

- Any significant disease that would put subject at risk through study participation

- BMI greater than 35

- Pacemaker

- Significantly abnormal ECG, Holter, or clinical lab finding (including Hepatitis B or
C)

- Cancer

- Allergy or hypersensitivity to anticholinergics or inhaler excipients

- Diseases that would contra-indicate the use of anticholinergics

- Use of oral corticosteroids within 6 weeks of screening

- Use of long-acting beta-agonists within 48 hours of screening

- Use of tiotropium within 14 days of screening

- Use of theophyllines or anti-leukotrienes within 48 hours of screening

- Use of short-acting bronchodilators within 4 to 6 hours of screening

- Use of investigational medicines within 30 days of screening

- Use of high dose inhaled corticosteroids

- Use of long-term oxygen therapy, CPAP or NIPPV

- Previous use of GSK573719