Dose Response of Umeclidinium 1-2x Daily in COPD
Dose Response of Umeclidinium 1-2x Daily in COPD
Cholinergic tone is considered the major reversible component of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). Receptor antagonism by antimuscarinic agents facilitates relaxation of airway smooth muscle. These agents bind to muscarinic receptor subtypes M1 and M3 localised in airway smooth muscle and block the bronchoconstrictor response to cholinergic nerve stimulation, thereby improving airflow obstruction. Long-acting muscarinic antagonists (LAMAs) have been shown to be a more effective and convenient treatment for COPD than short-acting bronchodilators.
Umeclidinium bromide (UMEC; GSK573719) is an inhaled LAMA in development for the treatment of COPD. Pharmacology studies have demonstrated that single- and repeat-dose UMEC administration is well tolerated in healthy volunteers and in patients with COPD. Statistically significant improvements in change from baseline in trough forced expiratory volume in 1 second (FEV1) were demonstrated compared with placebo. Although the dose–response curve of UMEC from 62.5 μg to 1000 μg has been examined over 14 and 28 days, the response obtained over this dosing range was relatively flat.
The current study examined the dose–response and safety of UMEC 15.6, 31.25, 62.5, and 125 μg administered once daily (QD), and UMEC 15.6 and 31.25 μg twice daily (BID). A model-based approach to the assessment of dose response has the advantage of utilising information within and across the range of doses studied for a more informed assessment of the drug's dose–response relationship. Preliminary results have been presented in abstract form.
Background
Cholinergic tone is considered the major reversible component of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). Receptor antagonism by antimuscarinic agents facilitates relaxation of airway smooth muscle. These agents bind to muscarinic receptor subtypes M1 and M3 localised in airway smooth muscle and block the bronchoconstrictor response to cholinergic nerve stimulation, thereby improving airflow obstruction. Long-acting muscarinic antagonists (LAMAs) have been shown to be a more effective and convenient treatment for COPD than short-acting bronchodilators.
Umeclidinium bromide (UMEC; GSK573719) is an inhaled LAMA in development for the treatment of COPD. Pharmacology studies have demonstrated that single- and repeat-dose UMEC administration is well tolerated in healthy volunteers and in patients with COPD. Statistically significant improvements in change from baseline in trough forced expiratory volume in 1 second (FEV1) were demonstrated compared with placebo. Although the dose–response curve of UMEC from 62.5 μg to 1000 μg has been examined over 14 and 28 days, the response obtained over this dosing range was relatively flat.
The current study examined the dose–response and safety of UMEC 15.6, 31.25, 62.5, and 125 μg administered once daily (QD), and UMEC 15.6 and 31.25 μg twice daily (BID). A model-based approach to the assessment of dose response has the advantage of utilising information within and across the range of doses studied for a more informed assessment of the drug's dose–response relationship. Preliminary results have been presented in abstract form.