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Methods

GSK2798745 was administered in a randomized, placebo-controlled study design to healthy volunteers in three separate cohorts as single escalating doses, with and without food, and as once-daily repeat doses for up to 14 days, respectively. Two cohorts of subjects with mild to moderate heart failure were also administered GSK2798745 once daily for up to 7 days. Safety, tolerability, and systemic exposure data were collected.

Results

No significant safety issues or serious adverse events were observed with GSK2798745 in healthy volunteers and patients with heart failure. GSK2798745 systemic exposure data demonstrated linear pharmacokinetics up to 12.5 mg, less than twofold accumulation with once-daily dosing, and a systemic half-life of~ 13 h. There was a slight increase in GSK2798745 exposure [14% increase in area under the plasma concentration–time curve (AUC) and 9% increase in …