GSK1325756 is a potent, competitive, selective and reversible CXCR2 receptor antagonist that is being developed as a once-daily oral anti-inflammatory medication for the treatment of chronic obstructive pulmonary disease (COPD). Selective antagonism of the interaction between CXCR2 and its various chemokine ligands is a potential strategy for reducing the underlying inflammation in COPD via the inhibition of neutrophil recruitment and activation. The current study explores the effects of age, gender and food (high fat meal) on the pharmacokinetics of GSK1325756. Because a significant proportion of COPD subjects are prescribed proton pump inhibitors (PPI's) such as omeprazole in order to alleviate symptoms of gastro-esophageal reflux disease (GERD), it is important to understand the absorption of the current formulation of GSK1325756 in an environment of raised intra-gastric pH as will be encountered in patients taking PPI's. Therefore, this study will also evaluate the impact of the proton pump inhibitor omeprazole on the pharmacokinetics of GSK1325756.
GSK1325756 is a potent, competitive, selective and reversible CXCR2 receptor antagonist that is being developed as a once-daily oral anti-inflammatory medication for the treatment of chronic obstructive pulmonary disease (COPD). Selective antagonism of the interaction between CXCR2 and its various chemokine ligands is a potential strategy for reducing the underlying inflammation in COPD via the inhibition of neutrophil recruitment and activation. The current study explores the effects of age, gender and food (high fat meal) on the pharmacokinetics of GSK1325756. Because a significant proportion of COPD subjects are prescribed proton pump inhibitors (PPI's) such as omeprazole in order to alleviate symptoms of gastro-esophageal reflux disease (GERD), it is important to understand the absorption of the current formulation of GSK1325756 in an environment of raised intra-gastric pH as will be encountered in patients taking PPI's. Therefore, this study will also evaluate the impact of the proton pump inhibitor omeprazole on the pharmacokinetics of GSK1325756.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
100mg of a single oral dose of GSK1325756 administered as 2 x 50mg tablets
100mg of a single oral dose of GSK1325756 administered as 2 x 50mg tablets
GSK Investigational Site
Minneapolis, Minnesota, United States
Pharmacokinetic parameters for GSK1325756 following the administration of a single dose of 100mg of a tablet formulation of GSK1325756 in the fed (after a high-fat meal) and fasted states in healthy adult subjects in the age range 40 to 64 y
Time frame: 48h of dosing
PK ofGSK1325756 following the administration of a single dose of 100mg of a tablet formulation of GSK1325756 given concomitantly with the final oral dose of 40mg omeprazole on the fifth day of repeat omeprazole dosing in healthy adult subjects 40-64y old
Time frame: 48h of dosing
PK parameters for GSK1325756 following the administration of a single dose of 100mg of a tablet formulation of GSK1325756 in the fasted state in healthy adult subjects in the age range 65 to 80 years
Time frame: 48h of dosing
Safety and tolerability of GSK1325756 alone in the fed and fasted states, alone and in combination with 40 mg omeprazole, as assessed by vital signs, ECGs, clinical laboratory data, clinical monitoring, and subject reports of adverse events.
Time frame: 7-14 days of dosing
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