Levoketoconazole treatment in endogenous Cushing’s syndrome: Extended evaluation of clinical, biochemical, and radiologic outcomes Journal Article
| Authors: | Fleseriu, M.; Auchus, R. J.; Greenman, Y.; Zacharieva, S.; Geer, E. B.; Salvatori, R.; Pivonello, R.; Feldt-Rasmussen, U.; Kennedy, L.; Buchfelder, M.; Biller, B. M. K.; Cohen, F.; Heaney, A. P. |
| Article Title: | Levoketoconazole treatment in endogenous Cushing’s syndrome: Extended evaluation of clinical, biochemical, and radiologic outcomes |
| Abstract: | Objective: 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. Design/Methods: SONICS included dose-titration (150–600 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 ≥2 mm denoted change from baseline in the largest tumor diameter. Results: 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 >3× upper limit of normal, Fridericia-corrected QT interval >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). Conclusion: 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. © 2022 The authors Published by Bioscientifica Ltd. |
| Keywords: | adult; controlled study; treatment outcome; cancer surgery; major clinical study; drug tolerability; fatigue; diarrhea; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; treatment duration; nuclear magnetic resonance imaging; outcome assessment; follow up; prospective study; quality of life; tumor volume; vomiting; qt prolongation; body weight; enzyme inhibitor; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; alanine aminotransferase; aspartate aminotransferase; drug induced headache; heart palpitation; hyperkalemia; hypokalemia; depression; body mass; enzyme inhibitors; multicenter study; ovary tumor; clinical evaluation; comorbidity; peripheral edema; limb pain; glucose blood level; hypoglycemia; open study; glucose; low density lipoprotein cholesterol; phase 3 clinical trial; hydrocortisone; drug dose titration; epilepsy; hyperlipidemia; somatostatin; rhinopharyngitis; neck pain; adrenal insufficiency; hirsutism; hypertransaminasemia; cushing syndrome; hyphema; hydrocortisone urine level; beck depression inventory; abdominal circumference; cushing disease; humans; human; male; female; article; patient history of radiotherapy; pituitary acth hypersecretion; qtc interval; levoketoconazole; blood biochemistry; pituitary macroadenoma; pituitary microadenoma |
| Journal Title: | European Journal of Endocrinology |
| Volume: | 187 |
| Issue: | 6 |
| ISSN: | 0804-4643 |
| Publisher: | BioScientifica Ltd. |
| Date Published: | 2022-12-01 |
| Start Page: | 859 |
| End Page: | 871 |
| Language: | English |
| DOI: | 10.1530/eje-22-0506 |
| PUBMED: | 36251618 |
| PROVIDER: | scopus |
| PMCID: | PMC9716395 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 January 2023 -- Source: Scopus |
