{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:15:30Z","timestamp":1793196930638,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":47,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This extended evaluation (EE) of the SONICS study assessed the effects of levoketoconazole for an additional 6 months following open-label, 6-month maintenance treatment in endogenous Cushing's syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design\/Methods<\/jats:title>\n                    <jats:p>SONICS included dose-titration (150\u2013600 mg BID), 6-month maintenance, and 6-month EE phases. Exploratory efficacy assessments were performed at months 9 and 12 (relative to the start of maintenance). For pituitary MRI in patients with Cushing's disease, a threshold of \u22652 mm denoted change from baseline in the largest tumor diameter.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixty patients entered EE at month 6; 61% (33\/54 with data) exhibited normal mean urinary free cortisol (mUFC). At months 9 and 12, respectively, 55% (27\/49) and 41% (18\/44) of patients with data had normal mUFC. Mean fasting glucose, total and LDL-cholesterol, body weight, BMI, abdominal girth, hirsutism, CushingQoL, and Beck Depression Inventory-II scores improved from the study baseline at months 9 and 12. Forty-six patients completed month 12; four (6.7%) discontinued during EE due to adverse events. The most common adverse events in EE were arthralgia, headache, hypokalemia, and QT prolongation (6.7% each). No patient experienced alanine aminotransferase or aspartate aminotransferase &amp;gt;3\u00d7 upper limit of normal, Fridericia-corrected QT interval &amp;gt;460 ms, or adrenal insufficiency during EE. Of 31 patients with tumor measurements at baseline and month 12 or follow-up, the largest tumor diameter was stable in 27 (87%) patients, decreased in one, and increased in three (largest increase 4 mm).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In the first long-term levoketoconazole study, continued treatment through a 12-month maintenance period sustained the early clinical and biochemical benefits in most patients completing EE, without new adverse effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/eje-22-0506","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T13:18:28Z","timestamp":1666012708000},"page":"859-871","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":35,"title":["Levoketoconazole treatment in endogenous Cushing's syndrome: extended evaluation of clinical, biochemical, and radiologic outcomes"],"prefix":"10.1093","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9284-6289","authenticated-orcid":false,"given":"Maria","family":"Fleseriu","sequence":"first","affiliation":[{"name":"Oregon Health and Science University , Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Auchus","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School , Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4923-488X","authenticated-orcid":false,"given":"Yona","family":"Greenman","sequence":"additional","affiliation":[{"name":"Tel Aviv University , Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Zacharieva","sequence":"additional","affiliation":[{"name":"Medical University-Sofia , Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza B","family":"Geer","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Salvatori","sequence":"additional","affiliation":[{"name":"Johns Hopkins University , Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9632-1348","authenticated-orcid":false,"given":"Rosario","family":"Pivonello","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Federico II di Napoli , Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-3355","authenticated-orcid":false,"given":"Ulla","family":"Feldt-Rasmussen","sequence":"additional","affiliation":[{"name":"Rigshospitalet, Copenhagen University Hospital , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Cleveland Clinic , Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Buchfelder","sequence":"additional","affiliation":[{"name":"University Hospital Erlangen , Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly M K","family":"Biller","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredric","family":"Cohen","sequence":"additional","affiliation":[{"name":"Xeris Biopharma Holdings, Inc. , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3865-0810","authenticated-orcid":false,"given":"Anthony P","family":"Heaney","sequence":"additional","affiliation":[{"name":"University of California Los Angeles School of Medicine , Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"2023012409095090400_bib1","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S2213-8587(21)00235-7","article-title":"Consensus on diagnosis and management of Cushing's disease: a guideline update","volume":"9","author":"Fleseriu","year":"2021","journal-title":"Lancet. 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