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

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, 4-week Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Repeat Inhaled Doses of the Combination of GSK233705 and GW642444 Administered Once-daily in Subjects With COPD

The purpose of this study is the evaluate the safety and tolerability of repeat dosing of the combination of inhaled GSK233705 and GW642444 administered once-daily in subjects with 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.