{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T15:13:06Z","timestamp":1793459586071,"version":"4.5.0"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T00:00:00Z","timestamp":1562112000000},"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":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>GPR109A (HM74A), a G\u2010protein\u2010coupled receptor, is hypothesized to mediate lipid and lipoprotein changes and dermal flushing associated with niacin administration. GSK256073 (8\u2010chloro\u20103\u2010pentyl\u20101H\u2010purine\u20102,6[3H,7H]\u2010dione) is a selective GPR109A agonist shown to suppress fatty acid levels and produce mild flushing in short\u2010term clinical studies. This study evaluated the effects of GSK256073 on lipids in subjects with low high\u2010density lipoprotein cholesterol (HDLc). Subjects (n\u00a0=\u00a080) were randomized (1:1:1:1) to receive GSK256073 5, 50, or 150\u00a0mg\/day or matching placebo for 8 weeks. The primary end point was determining the GSK256073 exposure\u2010response relationship for change from baseline in HDLc. No significant exposure response was observed between GSK256073 and HDLc levels. GSK256073 did not significantly alter HDLc levels versus placebo, but rather revealed a trend at the 150\u2010mg dose for a nonsignificant decrease in HDLc (\u20106.31%; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.12) and an increase in triglycerides (median, 24.4%; 95% confidence interval, 7.3%\u201041.6%). Flushing was reported in 21%, 25%, and 60% of subjects (5, 50, and 150\u00a0mg, respectively) versus 24% for placebo. Results indicated that selective activation of the GPR109A receptor with GSK256073 did not produce niacin\u2010like lipid effects. These findings add to the increasing evidence that niacin\u2010mediated lipoprotein changes occur predominantly via GPR109A\u2010independent pathways.<\/jats:p>","DOI":"10.1002\/cpdd.704","type":"journal-article","created":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T09:44:16Z","timestamp":1562147056000},"page":"871-883","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A Randomized, Placebo\u2010Controlled Trial to Assess the Effects of 8 Weeks of Administration of GSK256073, a Selective GPR109A Agonist, on High\u2010Density Lipoprotein Cholesterol in Subjects With Dyslipidemia"],"prefix":"10.1002","volume":"8","author":[{"given":"Eric J.","family":"Olson","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Experimental Medicine GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Mahar","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Modeling and Simulation GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Haws","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Experimental Medicine GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Fossler","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Modeling and Simulation GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Clinical Statistics, Metabolic Pathways and Cardiovascular Unit GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Charlotte","family":"de Gouville","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Laboratories Centre de Recherche Fran\u00e7ois Hyafil  Les Ulis Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis L.","family":"Sprecher","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Experimental Medicine GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Lepore","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Experimental Medicine GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2005.01528.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm824"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210695200"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16359-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.41.11.1400"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1991.tb00466.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm800258p"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.2001.280.3.E540"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003877"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300403-JLR200"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23626"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199908123410707"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011090"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27160"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.01.051"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701866200"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.03.005"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100235"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(98)00847-9"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.162.14.1568"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2204"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1185\/030079907X199637"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12132"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(98)90284-0"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115535"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.164541"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.02.029"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.704","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.704","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.704","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:27:05Z","timestamp":1694021225000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,3]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1002\/cpdd.704"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.704","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,3]]},"assertion":[{"value":"2019-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}