{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:17:26Z","timestamp":1793146646538,"version":"4.5.0"},"reference-count":7,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite advances in HIV\u20101 management with antiretroviral therapy, drug resistance and toxicities with multidrug regimens can result in treatment failure. Hence, there is a continuing demand for antiretroviral agents (ARVs) with novel mechanisms of action. Maturation inhibitors inhibit HIV\u20101 replication via a unique mechanism of action and can be combined with other ARVs. Two phase I randomized clinical trials were conducted for a maturation inhibitor, GSK3640254, to determine safety, pharmacokinetics (NCT03231943), and relative bioavailability (NCT03575962) in healthy adults. The first trial was conducted in two parts. Part 1 was conducted in a two\u2010cohort, interlocking, eight\u2010period fashion in 20 participants with single ascending doses of GSK3640254 (1\u2010700\u00a0mg) or placebo. In Part 2, 58 participants were randomized to receive GSK3640254 (n\u00a0=\u00a044) or placebo (n\u00a0=\u00a014). Four participants reported adverse events (AEs) leading to study discontinuation, with one adverse drug reaction (maculopapular rash). There was no relationship between frequency or severity of AEs and dose. Pharmacokinetic assessments showed that GSK3640254 was slowly absorbed, with time to maximum concentration (tmax) occurring between 3.5 and 4\u00a0hours and half\u2010life of\u00a0~24\u00a0hours. In the relative bioavailability study of GSK3640254 mesylate salt vs bis\u2010hydrochloride salt capsules in 14 healthy adults, the mesylate salt performed slightly better than the bis\u2010hydrochloride formulation (12%\u201016% increase in area under the concentration\u2010time curve and maximum concentration); tmax (5\u00a0hours) was similar between the formulations. Initial pharmacokinetic and safety data from these healthy\u2010participant studies informed further development of GSK3640254 for once\u2010daily dosing for the treatment of HIV\u20101 infection.<\/jats:p>","DOI":"10.1002\/prp2.671","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T12:23:55Z","timestamp":1605615835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Phase I evaluation of the safety, tolerability, and pharmacokinetics of GSK3640254, a next\u2010generation HIV\u20101 maturation inhibitor"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1332-5918","authenticated-orcid":false,"given":"Samit R.","family":"Joshi","sequence":"first","affiliation":[{"name":"ViiV Healthcare Branford CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Disala","family":"Fernando","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Clinical Unit Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Igwe","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Clinical Unit Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litza","family":"McKenzie","sequence":"additional","affiliation":[{"name":"Quotient Sciences Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anu S.","family":"Krishnatry","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Upper Providence PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Halliday","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Stockley Park UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Zhan","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Upper Providence PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Greene","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Upper Providence PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Upper Providence PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine","family":"Ferron\u2010Brady","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Upper Providence PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Lataillade","sequence":"additional","affiliation":[{"name":"ViiV Healthcare Branford CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherene","family":"Min","sequence":"additional","affiliation":[{"name":"ViiV Healthcare Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728220903039714"},{"key":"e_1_2_10_3_1","unstructured":"DeJesusE HarwardS JewellRC et al.A phase IIa study of novel maturation inhibitor GSK2838232 in HIV patients. Slides presented at: Conference on Retroviruses and Opportunistic Infections; March 4\u20137 2019; Seattle WA."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0205368"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328331c83b"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2015.05.004"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.22058"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.408"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.671","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.671","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.671","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T12:46:15Z","timestamp":1693658775000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,17]]},"references-count":7,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1002\/prp2.671"],"URL":"https:\/\/doi.org\/10.1002\/prp2.671","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,17]]},"assertion":[{"value":"2020-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00671"}}