Ketoconazole HRA is approved for endogenous Cushing's syndrome (CS). A post-authorization safety study (PASS) in 200 CS patients>12 years is ongoing to confirm Ketoconazole safety and effectiveness. Interim data are presented below.

Keto-PASS is a prospective open-label study using ERCUSYN registry, focusing on liver and cardiac tolerability, with overall safety and effectiveness as secondary parameters.

In all, 73 females and 20 males were included by August 2023. Median age was 47 years and 77.4% were pituitary-dependent CS. Median final dose was 400mg/day and treatment duration 212 days.

No QTc prolongation was reported. Liver function tests (LFT) abnormalities were reported in 37,5% occurring within the first months of treatment for most patients. No Hy's law cases were reported, 7 patients (8%) experienced LFTs above 5×ULN without bilirubin increase and assessed as hepatocellular (4), cholestatic (2) and mixed injury (1), resolving after drug discontinuation. In 05 patients, hepatotoxic drugs were co-administered.

In 5 patients, 9 other study-drug related serious adverse events occurred (pneumonia [1], acute kidney injury [2], hypokalemia [1], acute adrenal insufficiency [2], hyperkalemia [2], angioedema [1]). In patients where urinary free cortisol (UFC) and/or serum cortisol data were available at the last visit, 68.9% normalized UFC levels and/or serum cortisol. At the last visit, 13.2% of patients had at least one less drug for comorbidities. In 80% of patients the treatment was beneficial.

Keto-PASS confirms the tolerability profile already reported with Ketoconazole HRA. No serious cardiac and liver safety concerns have been reported so far.