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This \u201cscavenging\u201d activity creates concentration gradients of these ligands between blood vessels and tissues that drive directional cell migration. This randomized, double\u2010blind, placebo\u2010controlled first\u2010in\u2010human study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT\u20101004\u20101239, a first\u2010in\u2010class drug candidate small\u2010molecule CXCR7 antagonist. Food effect and absolute bioavailability assessments were also integrated in this multipurpose study. Healthy male subjects received single ascending oral doses of ACT\u20101004\u20101239 (<jats:italic>n<\/jats:italic>\u00a0=\u00a036) or placebo (<jats:italic>n<\/jats:italic>\u00a0=\u00a012). At each of six dose levels (1\u2013200\u00a0mg), repeated blood sampling was done over 144\u00a0hours for pharmacokinetic\/pharmacodynamic assessments using CXCL11 and CXCL12 as biomarkers of target engagement. ACT\u20101004\u20101239 was safe and well tolerated up to the highest tested dose of 200\u00a0mg. CXCL12 plasma concentrations dose\u2010dependently increased and more than doubled compared with baseline, indicating target engagement, whereas CXCL11 concentrations remained unchanged. An indirect\u2010response pharmacokinetic\/pharmacodynamic model well described the relationship between ACT\u20101004\u20101239 and CXCL12 concentrations across the full dose range, supporting once\u2010daily dosing for future clinical studies. At doses\u00a0\u2265\u00a010\u00a0mg, time to reach maximum plasma concentration ranged from 1.3 to 3.0\u00a0hours and terminal elimination half\u2010life from 17.8 to 23.6\u00a0hours. The exposure increase across the dose range was essentially dose\u2010proportional and no relevant food effect on pharmacokinetics was determined. The absolute bioavailability was 53.0% based on radioactivity data after oral vs. intravenous <jats:sup>14<\/jats:sup>C\u2010radiolabeled microtracer administration of ACT\u20101004\u20101239. 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