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

Eliza B. Geer, Roberto Salvatori, Atanaska Elenkova, Maria Fleseriu, Rosario Pivonello, Przemyslaw Witek, Richard A. Feelders, Marie Bex, Stina W. Borresen, Soraya Puglisi, Beverly M.K. Biller, Fredric Cohen, Francesca Pecori Giraldi

Research output: Contribution to journalArticlepeer-review

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 (US)
Pages (from-to)104-115
Number of pages12
JournalPituitary
Volume24
Issue number1
DOIs
StatePublished - Feb 2021

Keywords

  • Cushing’s disease
  • Cushing’s syndrome
  • Hypercortisolism
  • Quality of life
  • Steroidogenesis inhibitor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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