Dataset Information

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.

SUBMITTER: Fleseriu M

PROVIDER: S-EPMC9716395 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Levoketoconazole treatment in endogenous Cushing's syndrome: extended evaluation of clinical, biochemical, and radiologic outcomes.

Fleseriu Maria M Auchus Richard J RJ Greenman Yona Y Zacharieva Sabina S Geer Eliza B EB Salvatori Roberto R Pivonello Rosario R Feldt-Rasmussen Ulla U Kennedy Laurence L Buchfelder Michael M Biller Beverly Mk BM Cohen Fredric F Heaney Anthony P AP

European journal of endocrinology 20221124 6

<h4>Objective</h4>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.<h4>Design/methods</h4>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 ...[more]

PMID: 36251618

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Dataset Information

Levoketoconazole treatment in endogenous Cushing's syndrome: extended evaluation of clinical, biochemical, and radiologic outcomes.

Objective

Design/methods

Results

Conclusion

Publications

Levoketoconazole treatment in endogenous Cushing's syndrome: extended evaluation of clinical, biochemical, and radiologic outcomes.

Similar Datasets

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