{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:51:08Z","timestamp":1792036268279,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This Phase\u20091 program evaluated the safety, tolerability, pharmacokinetics and exploratory pharmacodynamics of the novel melanin\u2010concentrating hormone receptor\u20101 antagonist RGH\u2010706.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Study A was a first\u2010in\u2010man, randomized trial comprising a double\u2010blind, placebo\u2010controlled single\u2010ascending\u2010dose part (0.1\u2013162.5\u2009mg) and a two\u2010way crossover food\u2010effect assessment at 62.5\u2009mg in healthy men. Study\u2009B was a double\u2010blind, placebo\u2010controlled, single\u2010 and multiple\u2010ascending\u2010dose study in overweight or obese (otherwise healthy) men receiving a single dose followed by 14\u2009days of once\u2010daily dosing (2.5\u201322.5\u2009mg\/day). Safety assessments included clinical evaluations, ECGs and mood and sleep scales. RGH\u2010706 concentrations in plasma and urine samples were measured by validated methods. Pharmacokinetics was characterized using non\u2010compartmental analysis. Study\u2009B evaluated exploratory pharmacodynamic measures including appetite\u2010related outcomes, food preference, test\u2010meal food and macronutrient intake, body composition and metabolic biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In Study\u2009A (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200968), systemic exposure increased approximately dose proportionally up to 62.5\u2009mg and more than proportionally above, with\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      between 2.5 and 3.5\u2009h and a bi\u2010exponential disposition with a 29\u201335\u2009h terminal half\u2010life. Food ingestion had a negligible effect on exposure and renal clearance was also negligible. In Study\u2009B (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200936), RGH\u2010706 showed moderate accumulation with steady state reached within 8\u2009days. Exploratory pharmacodynamic measures showed a trend towards lower total energy intake, preference for fatty foods and weight gain, primarily with the lower doses of 2.5 and 7.5\u2009mg\/day. RGH\u2010706 was well tolerated across all doses and conditions in both studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RGH\u2010706 was safe, well tolerated and exhibited well\u2010characterized pharmacokinetics. The pharmacodynamic data support further exploration of RGH\u2010706 in weight management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71433","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:30:46Z","timestamp":1792035046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety, Tolerability, Pharmacokinetics and Exploratory Pharmacodynamics of Melanin\u2010Concentrating Hormone Receptor\u20101 Antagonist\n                    <scp>RGH\u2010706<\/scp>\n                    in Healthy and Overweight or Obese Men"],"prefix":"10.1111","author":[{"given":"Thomas","family":"Brevig","sequence":"first","affiliation":[{"name":"Global Medical Division Gedeon Richter Plc.  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borb\u00e1la","family":"Szepes","sequence":"additional","affiliation":[{"name":"Global Medical Division Gedeon Richter Plc.  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0390-4852","authenticated-orcid":false,"given":"Zs\u00f3fia Borb\u00e1la","family":"Dombi","sequence":"additional","affiliation":[{"name":"Global Medical Division Gedeon Richter Plc.  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7294-5894","authenticated-orcid":false,"given":"Gabriella","family":"Magyar","sequence":"additional","affiliation":[{"name":"Developmental Drug Metabolism &amp; Pharmacokinetics Gedeon Richter Plc.  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Juh\u00e1sz","sequence":"additional","affiliation":[{"name":"Developmental Drug Metabolism &amp; Pharmacokinetics Gedeon Richter Plc.  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margit","family":"Kap\u00e1s","sequence":"additional","affiliation":[{"name":"Developmental Drug Metabolism &amp; Pharmacokinetics Gedeon Richter Plc.  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"Cseh","sequence":"additional","affiliation":[{"name":"Developmental Drug Metabolism &amp; Pharmacokinetics Gedeon Richter Plc.  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsa","family":"Heged\u0171s","sequence":"additional","affiliation":[{"name":"Developmental Drug Metabolism &amp; Pharmacokinetics Gedeon Richter Plc.  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