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LOS ANGELES – An experimental treatment has improved the quality of life and reduced the symptoms of the disease in patients with endogenous Cushing syndrome, according to new findings from the Phase III study SONICS.
Patients taking oral levoketoconazole twice daily had significant reductions in mean scores for acne (-1.8), peripheral edema (-0.4) and l? hirsutism (-2.6), all secondary evaluation criteria of the pivotal test (PMaria Fleseriu, MD, of Oregon Health and Science University in Portland.
"We are looking forward to seeing the results of further studies and adding this therapy to the Cushing landscape," Fleseriu said at a presentation of the results at AACE 2019, the meeting said. annual meeting of the American Association of Clinical Endocrinologists. "We have a new drug and we still can not change Cushing's results, especially those reported by patients."
Free testosterone levels decreased significantly in women taking levoketoconazole (a steroid of ketoconazole and a potent inhibitor of steroidogenesis), from an average of 0.32 ng / dL to 0.12 ng / dL ( 0.011 to 0.004 nmol / L). P<0.0001). The men had a nonsignificant increase: 5.1 ng / dL up to 5.8 ng / dL (0.177 to 0.202 nmol / L).
No significant badysis was observed between the beginning and the end of maintenance for the other secondary endpoints of the badysis: lunar facies, facial plethora, streaks, bruising, supraclavicular fat, irregular menstruation and dysmenorrhea. However, significant improvements after 6 months of treatment were observed in the quality of life reported by patients compared to baseline values (mean change of 10.6 on Cushing's questionnaire on QoL), as well as a significant reduction in depressive symptoms (mean change of 4.3 on the Beck Depression Inventory II).
The open-label multicenter study SONICS (a study of levoketoconazole in Cushing's syndrome) included 94 adult men and women diagnosed with Cushing's syndrome with high mean levels of free urinary cortisol (mUFC). 24 hours were at least equal to Ordinary.
During the titration phase of the study dose (weeks 2 to 21), patients were titrated up to a maximum dose of 600 mg levocetoconazole twice daily until the standardization of the mUFC. A 6-month maintenance phase followed, with no increase in dose, but decreases were allowed if adverse effects occurred. An additional evaluation phase of six months was then followed.
The study achieved the previously stated primary endpoint: 30% of patients found normalized mUFC levels after 6 months of maintenance therapy with no dose escalation (95% CI 21% to 40%). P= 0.0154).
Levoketoconazole was well tolerated, with only 12.8% of patients discontinuing treatment due to adverse events. The most commonly reported adverse events were nausea (31.9%), headache (27.7%), peripheral edema (19.1%), high blood pressure (17%) and fatigue (16%). ), some of which were due to steroid withdrawal, Fleseriu told me.
Serious adverse events were reported in 14 patients, including prolonged QTc interval in two patients, elevated liver function in one patient and adrenal insufficiency in another, events similar to those seen with treatment with ketoconazole (Nizoral).
Fleseriu explained that the drug interaction is a problem in Cushing because all available medications prolong the QT interval.
She noted that in SONICS, a prolongation of the QT interval badociated with levoketoconazole was observed in some patients. It's still a "concern," said Fleseriu, especially for patients taking other drugs that prolong the QT interval.
Levoketoconazole, although it has not yet been approved, has received the orphan drug designation from the FDA and the European Medicines Agency for endogenous Cushing syndrome. The provisional brand name is Recorlev.
The study was funded by Strongbridge Biopharma.
Fleseriu has reported relationships with Strongbridge, Millendo Therapeutics and Novartis. The coauthors also revealed relevant relationships with the industry.
2019-04-26T12: 00: 00-0400
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