Levoketoconazole improves clinical signs and symptoms and patient-reported outcomes in patients with Cushing’s syndrome

EB Geer, R Salvatori, A Elenkova, M Fleseriu, R Pivonello, P Witek, R.A. Feelders, M Bex, SW Borresen, S Puglisi, BMK Biller, F Cohen, F Pecori Giraldi

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Abstract

Purpose: The efficacy of levoketoconazole in treating hypercortisolism was demonstrated in an open-label phase 3 study (SONICS) of adults with endogenous Cushing’s syndrome (CS) and baseline mean urinary free cortisol (mUFC) ≥ 1.5× ULN. Clinical signs and symptoms and patient-reported outcomes from the SONICS trial were evaluated in the current manuscript. Methods: Patients titrated to an individualized therapeutic dose entered a 6-month maintenance phase. Secondary endpoints included investigator-graded clinical signs and symptoms of CS during the maintenance phase, and patient-reported quality of life (CushingQoL questionnaire) and depression symptoms (Beck Depression Inventory II [BDI-II]). Results: Of 94 enrolled patients, 77 entered the maintenance phase following individualized dose titration. Significant mean improvements from baseline were noted at end of maintenance (Month 6) for acne, hirsutism (females only), and peripheral edema. These improvements were observed as early as Day 1 of maintenance for hirsutism (mean baseline score, 7.8; ∆ − 1.9; P < 0.0001), end of Month 1 for acne (mean baseline score, 2.8; ∆ − 1.2; P = 0.0481), and Month 4 for peripheral edema (mean baseline score, 1.0; ∆ − 0.5; P = 0.0052). Significant mean improvements from baseline were observed by Month 3 of maintenance for CushingQoL (mean baseline score, 44.3; ∆ + 6.9; P = 0.0018) and at Month 6 for BDI-II (mean baseline score, 17.1; ∆ − 4.3; P = 0.0043) scores. No significant mean improvement was identified in a composite score of 7 other clinical signs and symptoms. Conclusions: Treatment with levoketoconazole was associated with sustained, meaningful improvements in QoL, depression, and certain clinical signs and symptoms characteristic of CS. ClinialTrials.gov identifier: NCT01838551.

Original languageEnglish
Pages (from-to)104-115
Number of pages12
JournalPituitary
Volume24
Issue number1
DOIs
Publication statusPublished - Feb 2021

Bibliographical note

Funding Information:
The study was funded by Cortendo AB (a subsidiary of Strongbridge Biopharma).

Funding Information:
The authors thank the site investigators, study coordinators/nurses, clinical staff, and patients who participated in the study. Medical editorial assistance was provided by Nancy Holland, PhD, Synchrony Medical Communications, LLC, West Chester, PA; funding for this support was provided by Strongbridge Biopharma. Principal investigators (N=number of patients enrolled in the study): Belgium : Marie Bex (University Hospitals Leuven; N?=?3); Bulgaria : Sabrina Zacharieva (Acad. Ivan Penchev; N?=?6); Canada : Ehud Ur (St. Pauls Hospital/Vancouver General Hospital; N?=?1).

Funding Information:
EBG reports serving as an investigator for research grants to MSKCC from Ionis, Novartis, Corcept, and Strongbridge Biopharma. RS reports serving as the principal investigator of research grants to Johns Hopkins University from Novartis, Corcept, Crinetics, and Strongbridge Biopharma; and receiving consulting honoraria from Novo Nordisk. AE reports serving as the principal investigator/sub-investigator of clinical trials for Corcept Therapeutics and Novartis and receiving consulting honoraria from Novartis. MF reports serving as an investigator with research grants to OHSU for Millendo, Novartis, and Strongbridge Biopharma; and serving as an occasional consultant to Novartis and Strongbridge Biopharma. RP reports serving as the principal investigator of research grants to Federico II University from Corcept Therapeutics, Novartis, and Strongbridge Biopharma; and receiving consulting honoraria from Novartis and Strongbridge Biopharma. PW reports receiving travel grants from Ipsen and Novartis; and receiving personal fees as a clinical investigator from Ipsen, Novartis, Novo Nordisk, and Strongbridge Biopharma. RAF reports receiving research grants from Novartis; and serving on the speakers’ bureau for HRA Pharma and Novartis. MB reports receiving research grants from Strongbridge Biopharma. SWB reports no conflicts of interest. SP reports receiving research grants from HRA Pharma. BMKB reports serving as the principal investigator of research grants to Massachusetts General Hospital from Millendo, Novartis, and Strongbridge Biopharma; and serving as an occasional consultant to Novartis and Strongbridge Biopharma. FC reports being an employee of Strongbridge Biopharma. FPG reports receiving consulting honoraria from Novartis, HRA Pharma, and IBI-Lorenzini.

Funding Information:
The authors thank the site investigators, study coordinators/nurses, clinical staff, and patients who participated in the study. Medical editorial assistance was provided by Nancy Holland, PhD, Synchrony Medical Communications, LLC, West Chester, PA; funding for this support was provided by Strongbridge Biopharma.

Publisher Copyright:
© 2020, The Author(s).

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