This study is designed to assess whether inhibition of plasma Lp-PLA2 activity impacts platelet function as assessed by ex vivo platelet aggregation tests and in vivo plasma biomarkers.
SB-659032 is a selective and orally active inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) that is being developed for the treatment of atherosclerosis. This study is designed to assess whether inhibition of plasma Lp-PLA2 activity impacts platelet function as assessed by ex vivo platelet aggregation tests and in vivo plasma biomarkers. Blood samples for PK analysis and measurement of Lp-PLA2 activity will also be collected. Questionnaires will be completed to evaluate the frequency of odorrelated AEs with non-enteric coated formulation of SB-659032 relative to placebo. This will be a double blind, repeat dose, randomized, placebo-controlled, two period, period balanced, crossover study. There will be a minimum of a 21 day washout period between dosing in each period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
26
GSK Investigational Site
Randwick, Sydney, New South Wales, Australia
Platelet aggregation
Percent maximum platelet aggregation following ADP- and collagen-induced aggregation
Time frame: 14 days
Biomarkers of platelet aggregation
Urinary 11-dehydrothromboxane B2 and blood CD62 concentrations
Time frame: 14 days
Lp-PLA2 inhibition
Lp-PLA2 activity, expressed in terms of percent inhibition relative to baseline
Time frame: 14 days
Clinical safety data
spontaneous adverse event reporting, 12-Lead ECG, vital signs, nursing/physician observation and safety and laboratory tests
Time frame: 14 days
Mean concentrations of SB-659032 and its major metabolite, SB-664601
SB-659032 and SB-664601 concentrations
Time frame: 14 days
Frequency and intensity of odor-related adverse events
The frequency and intensity of odor-related adverse events as reported by subjects will be summarized
Time frame: 14 days
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