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Main outcome measures were pharmacodynamics (changes in growth hormone-releasing hormone [GHRH] stimulated growth hormone [GH] and insulin-like growth factor 1 [IGF-1]), pharmacokinetics, safety, and tolerability.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Single-dose cohorts: n\u2009=\u200941 active, n\u2009=\u200914 placebo. Multiple-dose cohorts: n\u2009=\u200924 active, n\u2009=\u200912 placebo. Paltusotine was well tolerated, orally bioavailable, associated with increased plasma concentrations to doses up to 40\u00a0mg, and was eliminated with a half-life of approximately 30\u00a0h. Single-dose paltusotine 1.25 to 20\u00a0mg suppressed GHRH-stimulated GH secretion by 44% to 93% compared to 15% with placebo. Multiple-dose paltusotine 5 to 30\u00a0mg administered once daily for 10\u00a0days suppressed IGF-1 by 19% to 37% compared to an increase of 2.4% with placebo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Paltusotine suppresses GH and IGF-1 in a dose-dependent fashion, with a safety profile similar to currently approved SST2 receptor ligands. Paltusotine is a promising once-daily oral nonpeptide SST2 agonist candidate for managing acromegaly and neuroendocrine tumors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>NCT03276858, registered September 8, 2017, retrospectively registered.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11102-021-01201-z","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T00:03:33Z","timestamp":1641686613000},"page":"328-339","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Paltusotine, a novel oral once-daily nonpeptide SST2 receptor agonist, suppresses GH and IGF-1 in healthy volunteers"],"prefix":"10.1007","volume":"25","clinical-trial-number":[{"clinical-trial-number":"nct03276858","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-2546","authenticated-orcid":false,"given":"Ajay","family":"Madan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Markison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Betz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Krasner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Jochelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Lickliter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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Betz, Alan Krasner, Rosa Luo, and R. Scott Struthe are employees of Crinetics Pharmaceuticals, Inc. Theresa Jochelson is a consultant for Crinetics Pharmaceuticals, Inc. Jason Lickliter is an employee of Nucleus Network.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The trial was conducted in accordance with Good Clinical Practice and the principles in the Declaration of Helsinki. The study was approved by the Alfred Hospital Ethics Committee (Melbourne, Australia).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Participants provided written informed consent before any study procedures.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All the authors vouch for the completeness and accuracy of the data and the analyses and for the fidelity of the trial to the protocol. All authors approved the final manuscript for submission. 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