Levoketoconazole treatment in endogenous Cushing’s syndrome: extended evaluation of clinical, biochemical, and radiologic outcomes
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 946 KB, PDF-dokument
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | European Journal of Endocrinology |
| Vol/bind | 187 |
| Udgave nummer | 6 |
| Sider (fra-til) | 859-871 |
| Antal sider | 13 |
| ISSN | 0804-4643 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
to Johns Hopkins University from Corcept Therapeutics; serving as an investigator with research grants to Johns Hopkins University from Crinetics and Strongbridge Biopharma; and serving as a consultant for HRA Pharma Rare Disease, 阀psen, NovoNordisk, Recordati Rare Diseases, and Strongbridge Biopharma. RP reports serving as the principal investigator of research grants to Federico II University from Corcept Therapeutics, Novartis, Recordati, and Strongbridge Biopharma; and receiving consulting honoraria from Novartis, Recordati, and Strongbridge Biopharma. UFR reports receiving speaker honoraria from Novartis, Novo Nordisk, and Pfizer; and serving on advisory boards for Novartis, Novo Nordisk, Recordati, and Pfizer. UFR’s research salary was sponsored by a grant from Kirsten and Freddy Johansen’s Fund. ?K reports serving as a principal investigator of research grants to the Cleveland Clinic from Chiasma, Crinetics, 阀onis, and Strongbridge Biopharma; receiving consulting honoraria from Corcept Therapeutics and Novo Nordisk; and receiving speaker fees from Corcept Therapeutics. MB reports receiving research grants to the University of Erlangen-Nuremberg from Strongbridge Biopharma. BMKB reports serving as the principal investigator of research grants to Massachusetts General Hospital from Strongbridge Biopharma; and receiving consulting honoraria from HRA Pharma, Novartis/Recordati, Sparrow, and Strongbridge Biopharma/Xeris Biopharma. FC is a former employee of Strongbridge Biopharma/Xeris Biopharma and reports receiving consulting fees from Xeris Biopharma. APH reports serving as a principal investigator of research grants to UC?A from Chiasma, Crinetics, 阀onis, Ascendis, and Strongbridge Biopharma; and receiving consulting honoraria from 阀psen, Novo Nordisk, ?undbeck, and Strongbridge Biopharma.
Funding Information:
This study was funded by Cortendo AB (a subsidiary of Strongbridge Biopharma (now Xeris Biopharma)).
Funding Information:
The authors thank the site investigators, study coordinators, clinical staff, and patients who participated in the study. Medical editorial assistance was provided under the direction of the authors by Nancy Holland, PhD, and Pratibha Hebbar, PhD, Synchrony Medical Communications, LLC, West Chester, PA. Funding for this support was provided by Strongbridge Biopharma. This study was funded by Cortendo AB (a subsidiary of Strongbridge Biopharma (now Xeris Biopharma)).
Funding Information:
The authors thank the site investigators, study coordinators, clinical sta 贀, and patients who participated in the study. Medical editorial assistance was provided under the direction of the authors by Nancy Holland, PhD, and Pratibha Hebbar, PhD, Synchrony Medical Communications, ??C, West Chester, PA. Funding for this support was provided by Strongbridge Biopharma.
Publisher Copyright:
© 2022 The authors Published by Bioscientifica Ltd.
ID: 340405580