Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Long acting muscarinic antagonist Tiotropium Chronic Bronchitis Emphysema Chronic Obstructive Pulmonary Disease
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 163
Healthy volunteers: no

Brief summary:
The purpose of this study is to further characterize the dose response of GSK573719 at doses of 15.6 micrograms (mcg) to 125 mcg once daily in patients with chronic obstructive pulmonary disease (COPD). Treatment with doses of GSK573719 dosed twice daily will also be included to further evaluate dosing frequency. Treatment with tiotropium (18 mcg) once daily via the Handihaler will be included as an active control. A placebo treatment will be included in order to evaluate absolute treatment effect of the different doses of GSK573719.

Detailed description:
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, three way crossover, incomplete block study to evaluate 4 doses of GSK573719 inhaled once daily and 2 doses of GSK573719 inhaled twice daily over 7 days in patients with COPD. Tiotropium will be included as an open label active comparator. A placebo treatment will be included to evaluate treatment effect of each GSK573719 dose. Pharmacokinetic profiles of GSK573719 will also be determined. Each eligible subject will receive a sequence of 3 of 8 potential treatments for a total of 3 treatment periods per subject. There will be 7 clinic visits, during three of which 24 hour serial spirometry will be performed. The total duration of subject participation is approximately 9 weeks.

Arms:
arm 1: 18 mcg, inhaled long acting muscarinic antagonist arm 2: inhaled medication arm 3: inactive/excipients only

Interventions: intervention 1: GSK573719 intervention 2: GSK573719 intervention 3: GSK573719 intervention 4: GSK573719 intervention 5: GSK573719 intervention 6: GSK573719 intervention 7: Tiotropium intervention 8: Placebo
Intervention descriptions: intervention 1: 125 mcg once daily intervention 2: 62.5 mcg once daily intervention 3: 31.25 mcg once daily intervention 4: 15.6 mcg once daily intervention 5: 31.25 mcg twice daily intervention 6: 15.6 mcg twice daily intervention 7: 18 mcg once daily intervention 8: once or twice daily

Protocol document: