{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T21:54:34Z","timestamp":1776290074136,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,6,10]],"date-time":"2017-06-10T00:00:00Z","timestamp":1497052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Selective androgen receptor modulators (SARMs) induce anabolic effects on muscle without the adverse effects of androgenic steroids. In this first\u2010in\u2010human study, we report the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of the SARM GSK2881078.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In Part A, healthy young men (<jats:italic>n<\/jats:italic> = 10) received a single dose of study drug (0\u00a0mg, 0.05\u00a0mg, 0.1\u00a0mg, 0.2\u00a0mg GSK2881078 or matching\u2010placebo). In Part B, repeat\u2010dose cohorts in men (<jats:italic>n<\/jats:italic> = 65) were 0.05\u00a0mg, 0.2\u00a0mg then 0.08\u00a0mg, 0.24\u00a0mg, 0.48\u00a0mg, 0.75\u00a0mg, or placebo; in women (<jats:italic>n<\/jats:italic> = 24) they were 0.24\u00a0mg, 0.35\u00a0mg, or placebo (7\u00a0days for 0.5\u00a0mg, 14\u00a0days for other doses).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PK analysis showed dose\u2010proportional increases in exposure and a long &gt;100\u2010h half\u2010life. No significant effects on vital signs, electrocardiograms, cardiac telemetry or standard clinical laboratory studies were observed. A dose\u2013response effect was observed on lowering both high\u2010density lipoprotein and sex hormone\u2010binding globulin. In females at 0.35\u00a0mg, differences from placebo were \u22120.518 (95% confidence interval: \u20130.703, \u22120.334) mmol l<jats:sup>\u20131<\/jats:sup> and \u221239.1 (\u221248.5, \u221229.7) nmol l<jats:sup>\u20131<\/jats:sup>, respectively. Women showed greater sensitivity to these parameters at lower doses than men. Drug\u2010related adverse events (AEs) were mild. One woman developed a drug rash and was withdrawn. Two men had elevated creatine phosphokinase after physical exertion during follow\u2010up. A serious AE occurred in a subject on placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data demonstrate pharmacodynamic effects with acceptable tolerability and support further clinical evaluation of this SARM.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13316","type":"journal-article","created":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T21:34:40Z","timestamp":1493328880000},"page":"2179-2194","source":"Crossref","is-referenced-by-count":47,"title":["Safety, pharmacokinetics and pharmacological effects of the selective androgen receptor modulator, GSK2881078, in healthy men and postmenopausal women"],"prefix":"10.1111","volume":"83","author":[{"given":"Richard V.","family":"Clark","sequence":"first","affiliation":[{"name":"Muscle Metabolism Discovery Performance Unit GlaxoSmithKline  Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann 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