{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:53:13Z","timestamp":1791337993285,"version":"4.3.1"},"reference-count":18,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T00:00:00Z","timestamp":1624060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Spruce Biosciences, Inc."},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is typically treated with lifelong supraphysiologic doses of glucocorticoids (GCs). Tildacerfont, a corticotropin-releasing factor type-1 receptor antagonist, may reduce excess androgen production, allowing for GC dose reduction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Assess tildacerfont safety and efficacy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Setting<\/jats:title>\n                  <jats:p>Two Phase 2 open-label studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>Adults with 21OHD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Intervention<\/jats:title>\n                  <jats:p>Oral tildacerfont 200 to 1000 mg once daily (QD) (n\u2005=\u200510) or 100 to 200 mg twice daily (n\u2005=\u20059 and 7) for 2 weeks (Study 1), and 400 mg QD (n\u2005=\u200511) for 12 weeks (Study 2).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measure<\/jats:title>\n                  <jats:p>Efficacy was evaluated by changes from baseline at 8 am in adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) according to baseline A4\u2005\u2264\u20052\u00d7 upper limit of normal (ULN) or A4\u2005&amp;gt;\u20052\u00d7 ULN. Safety was evaluated using adverse events (AEs) and laboratory assessments.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In Study 1, evaluable participants with baseline A4\u2005&amp;gt;\u20052\u00d7 ULN (n\u2005=\u200511; 19-67 years, 55% female) had reductions from baseline in ACTH (\u221259.4% to \u221228.4%), 17-OHP (\u221238.3% to 0.3%), and A4 (\u221224.2% to \u221218.1%), with no clear dose response. In Study 2, participants with baseline A4\u2005&amp;gt;\u20052\u00d7 ULN (n\u2005=\u20055; 26-63 years, 40% female) had ~80% maximum mean reductions in biomarker levels. ACTH and A4 were normalized for 60% and 40%, respectively. In both studies, participants with baseline A4\u2005\u2264\u20052\u00d7 ULN maintained biomarker levels. AEs (in 53.6% of patients overall) included headache (7.1%) and upper respiratory tract infection (7.1%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab438","type":"journal-article","created":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T13:39:17Z","timestamp":1624109957000},"page":"e4666-e4679","source":"Crossref","is-referenced-by-count":45,"title":["Tildacerfont in Adults With Classic Congenital Adrenal Hyperplasia: Results from Two Phase 2 Studies"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5741-3629","authenticated-orcid":false,"given":"Kyriakie","family":"Sarafoglou","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division 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