Endocrine Abstracts

Objective: To develop and validate the adult hypopituitarism questionnaire (AHQ) as a disease-specific, self-administered questionnaire for evaluation of QOL in adult patients with hypopituitarism.Methods: The development and validation of a new questionnaire were performed in a standardized manner: item development, pilot-testing and psychometric validation.Result: Content validity of the initial questionnaire was evaluated via tw...

Context: Osilodrostat (Osi), a potent inhibitor of 11β-hydroxylase, blocks the conversion of 11-deoxycortisol to cortisol and improves hypercortisolism in patients with Cushing’s syndrome (CS). Here, we report a study evaluating the efficacy of Osi in five non-Cushing’s disease (CD) CS patients treated with Osi in Japan.Subjects and Results: Five patients with non-CD CS were treated with Osi at Chiba University [primary disease breakdown: ...

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) ...

Background: Improving physical manifestations of hypercortisolism is an important treatment goal for patients with Cushing’s disease (CD). In the Phase III LINC 3 study (NCT02180217), osilodrostat therapy, a potent oral 11β-hydroxylase inhibitor, rapidly normalised mean urinary free cortisol (mUFC) in most patients with CD and sustained control of mUFC over a median treatment period of 130 weeks (W). Here we describe concomitant improvements in physical manifestation...

Introduction: Osilodrostat decreases cortisol production by inhibiting 11β-hydroxylase, increasing adrenal hormones above the blockade. Here, we describe these effects of osilodrostat and associated adverse events (AEs). The efficacy and safety of osilodrostat in patients with Cushing’s disease (CD) were confirmed in the published Phase III, prospective LINC 3 study (NCT02180217).Methods: 137 patients with CD (mUFC >1.5x upper limit of norm...

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...

IntroductionOsilodrostat, a potent oral 11β-hydroxylase inhibitor, normalized mean urinary free cortisol (mUFC) in most patients with CD during the 48-week (W) core phase of a Phase III study (LINC3: NCT02180217). We present efficacy and safety results following an extension to LINC3.MethodsCD patients with mUFC > 1.5× upper limit of normal (ULN) received osilodrostat during the core. Patients b...

Introduction: Osilodrosat is a potent oral 11β-hydroxylase inhibitor. During the 24-week, single-arm, open-label period of the Phase III LINC 3 study (NCT02180217), osilodrostat treatment demonstrated rapid, sustained reduction in mean urinary free cortisol (mUFC) in most Cushing disease (CD) patients. In the subsequent 8-week, double-blind, randomized-withdrawal phase, a significantly higher proportion of patients receiving osilodrostat maintained normal mUFC at week (W)...

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...

Introduction: In a Phase II study, osilodrostat, a potent oral 11β-hydroxylase inhibitor, normalized mean urinary free cortisol (mUFC) in most patients with CD. We report the efficacy and safety of osilodrostat in a large CD patient population (NCT02180217).Methods: In this study, open-label osilodrostat was initiated at 2 mg bid in 137 adults with CD and mUFC > 1.5 × ULN, with dose adjustments every 2 weeks (range 1–30 mg bid) up to ...