Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Combination of GSK573719 and GW642444 in Subjects With COPD

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study to
evaluate the safety and tolerability of the combination of GSK573719 (500mcg) Inhalation
Powder and GW642444 (25mcg) Inhalation Powder administered once-daily via a novel dry powder
inhaler (Novel DPI) over 28 days in subjects with COPD

Inclusion Criteria:

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

- Males or females of non-childbearing potential

- 40 or more 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 80% or less of predicted normal

Exclusion Criteria:

- Current diagnosis of asthma

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

- Previous lung resection surgery

- Significant abnormalities in chest x-ray presentation

- Use of oral steroids, antibiotics or hospitalization for a COPD exacerbation within 3
motnhs prior 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 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 or GW642444