{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:49:47Z","timestamp":1792082987747,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100018731","name":"Jiangsu Hengrui Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To assess the safety, tolerability, pharmacokinetics (PKs) and pharmacodynamics of HRS\u20107535, a novel glucagon\u2010like peptide\u20101 receptor agonist (GLP\u20101RA), in healthy participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This phase 1 trial consisted of single\u2010ascending dose (SAD), food effect (FE) and multiple\u2010ascending dose (MAD) parts. In the SAD part, participants were randomized (6:2) to receive HRS\u20107535 (at doses of 15, 60 and 120\u2009mg; administered orally once daily) or placebo. In the FE part, participants were randomized (8:2) to receive a single dose of 90\u2010mg HRS\u20107535 or placebo, in both fed and fasted states. In the MAD part, participants were randomized (18:6) to receive daily HRS\u20107535 (120\u2009mg [30\/60\/90\/120\u2010mg titration scheme]) or placebo for 28\u2009days. The primary endpoints were safety and tolerability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nausea and vomiting were the most frequently reported AEs across all three parts. In the SAD part, the median\n                      <jats:italic>T<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      was 5.98\u20105.99\u2009hours and the geometric mean\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>1\/2<\/jats:sub>\n                      was 5.28\u20109.08\u2009hours across the HRS\u20107535 dosing range. In the MAD part, the median\n                      <jats:italic>T<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      was 5.98\u201010.98\u2009hours and the geometric mean\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>1\/2<\/jats:sub>\n                      was 6.48\u20108.42\u2009hours on day 28 in participants on HRS\u20107535. PKs were approximately dose\u2010proportional. On day 29 in the MAD part, the mean (percentage) reduction in body weight from baseline was 4.38\u2009kg (6.63%) for participants who received HRS\u20107535, compared with 0.8\u2009kg (1.18%) for those participants who received a placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HRS\u20107535 exhibited a safety and tolerability profile consistent with other GLP\u20101RAs and showed PKs suitable for once\u2010daily dosing. These findings support further clinical development of HRS\u20107535 for type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15383","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T12:47:15Z","timestamp":1702644435000},"page":"901-910","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Safety, pharmacokinetics and pharmacodynamics of\n                    <scp>HRS<\/scp>\n                    \u20107535, a novel oral small molecule glucagon\u2010like peptide\u20101 receptor agonist, in healthy participants: A phase 1, randomized, double\u2010blind, placebo\u2010controlled, single\u2010 and multiple\u2010ascending dose, and food effect trial"],"prefix":"10.1111","volume":"26","author":[{"given":"Jingying","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology The Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renpeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology The Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology The Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology The Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology The Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Ye","sequence":"additional","affiliation":[{"name":"Clinical Research and Development Jiangsu Hengrui Pharmaceuticals Co., Ltd.  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