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Thirty\u2010five healthy men (age 38.2\u00a0\u00b1\u00a010.4\u00a0years; body mass index 24.8\u00a0\u00b1\u00a03.1\u00a0kg\u00a0m<jats:sup>\u20132<\/jats:sup> [mean\u00a0\u00b1\u00a0standard deviation]) received \u22651 dose (2, 10, 40 [divided], 50, 100, 150, and 300 [single or divided] mg) of PF\u201005190457 and\/or placebo in the SAD. In the MAD study, 35 healthy men (age 39.7\u00a0\u00b1\u00a010.1\u00a0years; body mass index 25.9\u00a0\u00b1\u00a03.3\u00a0kg\u00a0m<jats:sup>\u20132<\/jats:sup>) received \u22651 dose (2, 10, 40 and 100\u00a0mg twice daily) of PF\u201005190457 and\/or placebo daily for 2\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PF\u201005190457 absorption was rapid with a T<jats:sub>max<\/jats:sub> of 0.5\u20133\u00a0hours and a half\u2010life between 8.2\u20139.8\u00a0hours. PF\u201005190457 dose\u2010dependently blocked ghrelin (1\u00a0pmol\u00a0kg<jats:sup>\u20131<\/jats:sup>\u00a0min<jats:sup>\u20131<\/jats:sup>)\u2010induced growth hormone (GH) release with (mean [90% confidence interval]) 77% [63\u201385%] inhibition at 100\u00a0mg. PF\u201005190457 (150\u00a0mg) delayed gastric emptying lag time by 30% [7\u201358%] and half emptying time by 20% [7\u201335%] with a corresponding decrease in postprandial glucose by 9\u00a0mg\u00a0dL<jats:sup>\u20131<\/jats:sup>. The most frequent adverse event reported by 30 subjects at doses \u226550\u00a0mg was somnolence. PF\u201005190457 plasma concentrations also increased heart rate up to 13.4 [4.8\u201358.2] beats\u00a0min<jats:sup>\u20131<\/jats:sup> and, similar to the effect on glucose and ghrelin\u2010induced GH, was lost within 2\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PF\u201005190457 is a well\u2010tolerated first\u2010in\u2010class ghrelin receptor inverse agonist with acceptable pharmacokinetics for oral daily dosing. Blocking ghrelin receptors inhibits ghrelin\u2010induced GH, and increases heart rate, effects that underwent tachyphylaxis with chronic dosing. 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