Endocrine Abstracts

Background: Osilodrostat is an oral inhibitor of 11β-hydroxylase (CYP11B1), the enzyme that catalyses the final step in cortisol biosynthesis. In a 22-week, phase II study, osilodrostat treatment normalised mean urinary free cortisol (mUFC) in 78.9% (15/19) of patients with uncontrolled Cushing’s disease and was well tolerated. The present phase 3 study is designed to confirm the safety and efficacy of osilodrostat in patients with uncontrolled Cushing’s disease...

Introduction: Osilodrostat is a potent, oral inhibitor of 11β-hydroxylase, the enzyme that catalyses final step of cortisol biosynthesis. In a phase II study, 15/19 patients treated with osilodrostat met the primary endpoint (normal urinary free cortisol (UFC) at 22 weeks); osilodrostat was generally well tolerated. This phase III study aims to confirm the efficacy and long-term safety of osilodrostat.Patients and methods: Adults (18–75 years) ...

Introduction: In vitro assessments of osilodrostat (LCI699), a potent oral inhibitor of 11β-hydroxylase suggested potential drug–drug interactions (DDIs) with cytochrome P450 (CYP) enzyme metabolism. This clinical study evaluated the effect of osilodrostat on the pharmacokinetics (PK) of CYP1A2, CYP2C19, CYP2D6, and CYP3A4 probe substrates, caffeine, omeprazole, dextromethorphan, and midazolam, respectively.Methods: A single-centre, op...

Background: In the 22-week LINC-2 study, osilodrostat (LCI699), a potent oral 11β-hydroxylase inhibitor, normalized urinary free cortisol (UFC) levels in 15 of 19 patients with Cushing’s disease (CD). The most common AEs were nausea, diarrhea, asthenia, and adrenal insufficiency (n=6 each). Here, we report the 31-month efficacy and safety results from LINC-2 extension.Methods: Patients receiving clinical benefit at week 22 could enter ...

Background: A proof-of-concept study (LINC 1) demonstrated that after 10 weeks, LCI699 normalized UFC in 11/12 patients with Cushing’s disease. This interim analysis of the first eight patients enrolled into a longer-term study (LINC 2) further evaluates LCI699 in Cushing’s disease; the full analysis on all 19 enrolled patients is expected in time for the congress.Methods: There were two study groups. Previous LINC 1 participants (follow-up coh...

Introduction: During the 22-week LINC-2 study, the potent oral 11β-hydroxylase inhibitor osilodrostat normalized UFC in 15/19 (78.9%) patients with Cushing’s disease. Most common AEs were nausea, diarrhoea, asthenia, and adrenal insufficiency. This report describes 19-month results following an extension.Methods: Patients who were receiving clinical benefit at week 22 could enter the extension. Efficacy/safety is reported for patients who enter...