Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of GSK573719 (LAMA) and GW642444 (LABA)Administered Individually and Concurrently in Healthy Japanese Subjects
Summary
GW642444 is a potent and selective long-acting beta2 agonist; GSK573719 is a long-acting, inhaled, muscarinic receptor antagonist (or anticholinergic) bronchodilator. Both are in development as once daily (QD) monotherapies for the treatment of Chronic Obstructive Pulmonary Disease (COPD). Development of these two inhaled drugs as a combination therapy is also planned and would have potential for improved efficacy and patient benefit as they both work through different receptor pathways and the combined bronchodilatory effect might be additive.
This study is a randomised, double blind, placebo-controlled, four-way crossover study which will assess the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of GSK573719 and GW642444 in sixteen healthy Japanese subjects. Subjects will receive four possible treatments as single inhaled doses, receiving the two monotherapies separately, the monotherapies concurrently, and placebo.
Blood samples for PK analysis will be taken at regular intervals after dosing. Safety will be assessed by measurement of heart rate, blood pressure, ECG and twenty-four hour Holter monitoring, potassium, safety laboratory data and review of adverse events.
Study Design
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Conditions
Chronic Obstructive Pulmonary Disease (COPD)
Intervention
GSK573719
Location
GSK Investigational Site
Randwick
New South Wales
Australia
2031
Status
Completed
Source
GlaxoSmithKline
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00976144
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Pulmonary Disease, Chronic Obstructive
A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.
Pulmonary Heart Disease
Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.
Bronchitis, Chronic
A subcategory of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis.
Sleep Apnea, Central
A condition associated with multiple episodes of sleep apnea which are distinguished from obstructive sleep apnea (SLEEP APNEA, OBSTRUCTIVE) by the complete cessation of efforts to breathe. This disorder is associated with dysfunction of central nervous system centers that regulate respiration. This condition may be idiopathic (primary) or associated with lower brain stem lesions; chronic obstructive pulmonary disease (LUNG DISEASES, OBSTRUCTIVE); HEART FAILURE, CONGESTIVE; medication effect; and other conditions. Sleep maintenance is impaired, resulting in daytime hypersomnolence. Primary central sleep apnea is frequently associated with obstructive sleep apnea. When both forms are present the condition is referred to as mixed sleep apnea (see SLEEP APNEA SYNDROMES). (Adams et al., Principles of Neurology, 6th ed, p395; Neurol Clin 1996;14(3):611-28)
Plethysmography, Whole Body
Measurement of the volume of gas in the lungs, including that which is trapped in poorly communicating air spaces. It is of particular use in chronic obstructive pulmonary disease and emphysema. (Segen, Dictionary of Modern Medicine, 1992)
Clinical Trials
Safety Study Using GSK573719 And Tiotropium In Patients With Chronic Obstructive Pulmonary Disease
GSK573719 is a high-affinity specific muscarinic receptor (mAChR) antagonist which is being developed for once daily treatment of chronic obstructive pulmonary disease (COPD). The long du...
GSK573719 is a high-affinity specific muscarinic receptor (mAChR) antagonist which is being developed for once daily treatment of chronic obstructive pulmonary disease (COPD). The long du...
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Chronic obstructive pulmonary disease (COPD) is a condition that is characterized by blockage of the airways due to inflammation. Levels of inflammatory proteins may be linked to when and...
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