{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:19:58Z","timestamp":1789885198838,"version":"4.0.1"},"reference-count":8,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Replacement therapy with modified\u2010release hydrocortisone capsules (MRHC) restores the physiological circadian cortisol rhythm in congenital adrenal hyperplasia (CAH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To determine the relative bioavailability of MRHC and evaluate an optimal protocol to switch CAH patients from standard therapy to MRHC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>(1): Crossover study in healthy participants comparing relative bioavailability of MRHC with immediate\u2010release hydrocortisone (IRHC). (2): Post hoc analysis of first 4 weeks of phase 3 MRHC study when CAH patients were switched to MRHC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010four healthy male participants completed the relative bioavailability study: 20\u2009mg MRHC showed comparable bioavailability to 20\u2009mg IRHC tablets; mean AUC<jats:sub>0\u2212inf<\/jats:sub> was 2650 versus 2450\u2009h*nmol\/L, ratio of 108% (90% confidence interval (CI) 103%\u2212113%). In the phase 3 study, 122 CAH patients were recruited of which 63 patients were managed with IRHC alone at baseline; 31 of 63 were randomised to continue IRHC and 32 of 63 were randomised to switch to MRHC on the same daily dose but given twice daily. At 4 weeks, a greater reduction in both the 09:00\u2009h 17\u2010hydroxyprogesterone and androstenedione was observed in the MRHC group compared to the IRHC group; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 and <jats:italic>p<\/jats:italic>\u2009=\u20090.01, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MRHC showed comparable bioavailability to IRHC based on cortisol AUC after 20\u2009mg administration. Switching patients treated with IRHC to a twice daily MRHC regimen on the same daily dose (giving approximately two thirds of the dose at night) is an effective protocol for starting MRHC treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.15275","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T08:04:45Z","timestamp":1747382685000},"page":"290-293","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Switching Patients With Congenital Adrenal Hyperplasia to Modified\u2010Release Hydrocortisone Capsules: Relative Bioavailability and Disease Control"],"prefix":"10.1111","volume":"103","author":[{"given":"Richard John M.","family":"Ross","sequence":"first","affiliation":[{"name":"University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5106-9719","authenticated-orcid":false,"given":"Wiebke","family":"Arlt","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Medical Sciences London UK"},{"name":"Institute of Clinical Sciences, Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude Brac","family":"de la Perriere","sequence":"additional","affiliation":[{"name":"Hopital Louis Pradel Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6481-6277","authenticated-orcid":false,"given":"Angelica Lind\u00e9n","family":"Hirschberg","sequence":"additional","affiliation":[{"name":"Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0534-4350","authenticated-orcid":false,"given":"Anders","family":"Juul","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-0460","authenticated-orcid":false,"given":"Deborah P.","family":"Merke","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D. C.","family":"Newell\u2010Price","sequence":"additional","affiliation":[{"name":"University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4821-0336","authenticated-orcid":false,"given":"Alessandro","family":"Prete","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and Systems Research University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1165-9092","authenticated-orcid":false,"given":"D. Aled","family":"Rees","sequence":"additional","affiliation":[{"name":"Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7469-6069","authenticated-orcid":false,"given":"Nicole","family":"Reisch","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV, LMU Klinikum M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5268-9370","authenticated-orcid":false,"given":"Monica","family":"Stikkelbroeck","sequence":"additional","affiliation":[{"name":"Radboud Univ Nijmegen Med Ctr Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8462-7753","authenticated-orcid":false,"given":"Philippe A.","family":"Touraine","sequence":"additional","affiliation":[{"name":"H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re Sorbonne Universit\u00e9 Paris Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Maltby","sequence":"additional","affiliation":[{"name":"Neurocrine UK Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Quirke","sequence":"additional","affiliation":[{"name":"Neurocrine UK Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5244-4670","authenticated-orcid":false,"given":"Helen","family":"Coope","sequence":"additional","affiliation":[{"name":"Neurocrine UK Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Porter","sequence":"additional","affiliation":[{"name":"Neurocrine UK Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01865"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12086"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12345"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-3809"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab026"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2005.04.012"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.4172\/jbb.1000371"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1926"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.15275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T05:32:22Z","timestamp":1754285542000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.15275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,16]]},"references-count":8,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/cen.15275"],"URL":"https:\/\/doi.org\/10.1111\/cen.15275","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,16]]},"assertion":[{"value":"2025-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}