This is a multi-center, randomized, blinded, placebo controlled study to evaluate the safety of GSK1278863 and its acute and short-term (e.g. 14d) effects on calf muscle endurance and walking ability in subjects with PAD and symptomatic claudication. Functional assessments will be performed following a single high dose (300mg), a single low dose (15mg), and following 14 days of low dose treatment (15mg q.d.). The objectives of this study are to: 1) Evaluate the safety and tolerability of GSK1278863 administered as a single dose and as sub-chronic low dosing (i.e. 14 days) in subjects with peripheral artery disease; 2) To demonstrate the potential pharmacodynamic effect of GSK1278863 on functional measures of calf muscle endurance and fatigability and timed walking distance following a single high or low dose and after 14 days of multiple low dose administration in subjects with claudication-limited peripheral artery disease. In this hypothesis-generating study, multiple assessments of ambulatory and skeletal muscle function will be made during standardized tests of claudication-limited exercise performance, and 3). Characterize the relationship, if any, between the doses and plasma concentrations of GSK1278863 and the pharmacodynamic effects.