{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T23:42:42Z","timestamp":1771630962101,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,5,18]],"date-time":"2015-05-18T00:00:00Z","timestamp":1431907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>This phase <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content> healthy volunteer study (<jats:styled-content style=\"fixed-case\">NCT01031589<\/jats:styled-content>) was carried out to investigate the safety\/tolerability and pharmacokinetics of a rilpivirine (<jats:styled-content style=\"fixed-case\">RPV<\/jats:styled-content>; <jats:styled-content style=\"fixed-case\">TMC278<\/jats:styled-content>) long\u2010acting (<jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content>) formulation after single and multiple intramuscular (<jats:styled-content style=\"fixed-case\">IM<\/jats:styled-content>) injections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>n the first part of the study, which had an open\u2010label design, a single <jats:styled-content style=\"fixed-case\">RPV LA IM<\/jats:styled-content> injection (300\u2009mg\/mL) of 300 (<jats:italic>n<\/jats:italic>\u2009=\u20096) or 600 (<jats:italic>n<\/jats:italic>\u2009=\u20095) mg was given to the volunteers. In the second part of the study, which had a double\u2010blind, randomized, placebo\u2010controlled design, three <jats:styled-content style=\"fixed-case\">RPV LA IM<\/jats:styled-content> injections (one every 4 weeks) at 1200\/600\/600\u2009mg (<jats:italic>n<\/jats:italic>\u2009=\u20096) or placebo (<jats:italic>n<\/jats:italic>\u2009=\u20092) were given. Safety and local tolerability were monitored. <jats:styled-content style=\"fixed-case\">RPV<\/jats:styled-content> plasma concentrations were analysed up to 28 days after injection or until they were &lt;\u200920\u2009ng\/mL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Grade 1\/2 <jats:styled-content style=\"fixed-case\">RPV<\/jats:styled-content>\u2010related adverse events in the 300, 600 and 1200\/600\/600\u2009mg groups were: rash (zero, one and one subject, respectively, the last of whom discontinued participation in the study); musculoskeletal stiffness (three, zero and zero subjects, respectively); injection site reactions (one, two and two subjects, respectively). After one injection of 300, 600 or 1200\u2009mg <jats:styled-content style=\"fixed-case\">RPV LA<\/jats:styled-content>, the mean (standard deviation) maximum plasma concentration was 39 (25), 48 (13) and 140 (16) ng\/mL, and the mean (standard deviation) area under the concentration\u2013time curve (28 days) was 17\u2009090 (8907), 25\u2009240 (8184) and 55\u2009350 (13\u2009550) ng h\/mL, respectively. <jats:styled-content style=\"fixed-case\">RPV<\/jats:styled-content> pharmacokinetics were largely comparable after the 1200\u2009mg loading dose and both 600\u2009mg injections of <jats:styled-content style=\"fixed-case\">RPV LA<\/jats:styled-content>. The mean (standard deviation) <jats:styled-content style=\"fixed-case\">RPV<\/jats:styled-content> plasma concentration across the 28\u2010day dosing interval after the last injection in the 1200\/600\/600\u2009mg group was 79 (19) ng\/mL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Single and multiple <jats:styled-content style=\"fixed-case\">IM<\/jats:styled-content> injections of <jats:styled-content style=\"fixed-case\">RPV LA<\/jats:styled-content> demonstrated favourable local\/systemic tolerability in healthy volunteers. <jats:styled-content style=\"fixed-case\">RPV<\/jats:styled-content> pharmacokinetics suggested that clinically relevant plasma concentrations can be achieved with this <jats:styled-content style=\"fixed-case\">LA<\/jats:styled-content> formulation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hiv.12247","type":"journal-article","created":{"date-parts":[[2015,5,18]],"date-time":"2015-05-18T11:35:49Z","timestamp":1431948949000},"page":"477-484","source":"Crossref","is-referenced-by-count":48,"title":["Safety, tolerability and pharmacokinetics of rilpivirine following administration of a long\u2010acting formulation in healthy volunteers"],"prefix":"10.1111","volume":"16","author":[{"given":"R","family":"Verloes","sequence":"first","affiliation":[{"name":"Janssen Infectious Diseases BVBA  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Deleu","sequence":"additional","affiliation":[{"name":"Janssen Clinical Pharmacology Unit  Merksem Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Niemeijer","sequence":"additional","affiliation":[{"name":"Janssen Infectious Diseases BVBA  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Crauwels","sequence":"additional","affiliation":[{"name":"Janssen Infectious Diseases BVBA  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Meyvisch","sequence":"additional","affiliation":[{"name":"Janssen Infectious Diseases BVBA  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Williams","sequence":"additional","affiliation":[{"name":"Janssen Infectious Diseases BVBA  Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,5,18]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Edurant\u00ae(rilpivirine) tablets US prescribing information. 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