Safety and Tolerability of Repeat Dosing of GSK233705/GW642444 in COPD

Inclusion Criteria:

- male and females 40 to 80 years of age (inclusive)

- COPD diagnosis

- Current or previous smokers with a cigarette smoking history of at least 10 pack-

- Post-albuterol FEV1/FVC of 0.70 or less

- Post-albuterol FEV1 of 35% to 80% (inclusive)

Exclusion Criteria:

- Pregnant or lactating females

- current diagnosis of asthma

- respiratory disorders other than COPD

- clinically significant cardiovascular, neurological, psychiatric, renal,
immunological, endocrine, or hematological abnormalities that are uncontrolled

- clinically significant sleep apnea

- previous lung resection surgery

- clinically significant abnormalities confirmed by chest x-ray that are not related to
COPD

- hospitalization for COPD within 3 months of screening

- use of antibiotics for lower respiratory tract infection within 6 months of screening

- abnormal and clinically significant 12-lead ECG findings

- current malignancy in remission for less that 5 years

- medical conditions that would contraindicate the use of anticholinergics

- positive hepatitis B or C test

- history of alcohol or drug abuse

- unable to withhold albuterol for 6 or more hours

- use of long term oxygen therapy

- conditions that would limit the validity of informed consent

- use of GW642444 or GSK233705 in previous studies

- use of an investigation drug with 30 days of screening

- use of inhaled corticosteroids (ICS) at a dose greater than 1000mcg of fluticasone
propionate or equivalent

- hypersensitivity to beta-agonists

- concurrent use of long-acting beta-agonists (LABA) or long-acting muscaring
antagonists, LABA/ICS combination products, cytochrome p450 inhibitors, oral or depot
corticosteroids, theophyllines, oral beta agonists, oral leukotrine modulators,
inhaled short acting anticholinergics.