Levoketoconazole treatment in endogenous Cushing’s syndrome: extended evaluation of clinical, biochemical, and radiologic outcomes
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Levoketoconazole treatment in endogenous Cushing’s syndrome : extended evaluation of clinical, biochemical, and radiologic outcomes. / Fleseriu, Maria; Auchus, Richard J.; Greenman, Yona; Zacharieva, Sabina; Geer, Eliza B.; Salvatori, Roberto; Pivonello, Rosario; Feldt-Rasmussen, Ulla; Kennedy, Laurence; Buchfelder, Michael; Biller, Beverly M.K.; Cohen, Fredric; Heaney, Anthony P.
In: European Journal of Endocrinology, Vol. 187, No. 6, 2022, p. 859-871.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Levoketoconazole treatment in endogenous Cushing’s syndrome
T2 - extended evaluation of clinical, biochemical, and radiologic outcomes
AU - Fleseriu, Maria
AU - Auchus, Richard J.
AU - Greenman, Yona
AU - Zacharieva, Sabina
AU - Geer, Eliza B.
AU - Salvatori, Roberto
AU - Pivonello, Rosario
AU - Feldt-Rasmussen, Ulla
AU - Kennedy, Laurence
AU - Buchfelder, Michael
AU - Biller, Beverly M.K.
AU - Cohen, Fredric
AU - Heaney, Anthony P.
N1 - Publisher Copyright: © 2022 The authors Published by Bioscientifica Ltd.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1530/EJE-22-0506
DO - 10.1530/EJE-22-0506
M3 - Journal article
C2 - 36251618
AN - SCOPUS:85143088526
VL - 187
SP - 859
EP - 871
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 6
ER -
ID: 340405580