Biochemical markers and clinical signs and symptoms of endogenous Cushing syndrome improved after 6 months of levoketoconazole therapy, according to phase 3 study results presented at the 28th Annual Congress of the American Association of Clinical Endocrinologists, held April 24 to 28, 2019, in Los Angeles, California.
This phase 3 multicenter open-label study enrolled patients with Cushing syndrome who had a mean 24-hour urinary free cortisol ≥1.5 times the upper limit of normal. The study had 3 phases: (1) dose titration (2-21 weeks), including treatment with levoketoconazole (150-600 mg, twice daily) as needed to achieve normalization of mean urinary free cortisol; (2) maintenance phase (6 months); and (3) extended evaluation phase (6 months).
The primary end point results — reduction in mean urinary free cortisol and safety after the 6-month maintenance phase — were previously presented at the European Neuroendocrine Association meeting in 2018. Secondary end points included changes in Cushing clinical signs and symptoms from baseline to end of the maintenance phase.
Of 94 participants (82% women; mean age, 44 ± 13 years; mean urinary free cortisol at baseline, 4.9 times the upper limit of normal), 77 entered the maintenance phase. These data were used for the current secondary end point analysis.
Treatment with levoketoconazole was associated with significant mean improvements from baseline in the following areas: acne (difference of -1.8 in acne score; P =.0063), hirsutism in women (difference of -2.6 in hirsutism score; P =.0008), peripheral edema (difference of -0.4 in peripheral edema score; P =.0295), quality of life (difference of 10.6 in Cushing quality of life questionnaire score; P <.0001), and depression (difference of -4.3 in Beck Depression Inventory II score; P =.0043).
In addition to the clinical improvements, there was also biochemical improvement following levoketoconazole treatment. Mean free testosterone levels decreased significantly in women (0.3 to 0.1 ng/dL; P <.0001), but no significant change was noted in men.
Approximately one-third of patients (35%) discontinued levoketoconazole treatment by the end of maintenance phase, including 12 patients (13%) who stopped the treatment because of adverse events.
“Clinical signs and symptoms of [Cushing syndrome]… improved following 6 months of levoketoconazole therapy. Improvements in biochemical markers of efficacy including reduction in urinary cortisol and free testosterone (in women) were also observed,” stated the researchers.
Fleseriu M, Pivonello R, Elenkova A, et al. Levoketoconazole in the treatment of endogenous Cushing’s syndrome: improvements in clinical signs and symptoms, patient-reported outcomes, and associated biochemical markers in the phase 3 SONICS study. Presented at: American Association of Clinical Endocrinologists 28th Annual Scientific & Clinical Congress; April 24-28, 2019; Los Angeles, CA.