Endocrine Abstracts

Introduction: Patients with adrenal insufficiency (AI) (primary (PAI), secondary to pituitary disease (PIT) and congenital adrenal hyperplasia (CAH)) have reduced life expectancy with reported standardized mortality ratios of ~2:1 but given the rarity of AI, the underlying explanation remains largely unknown.Objective: To evaluate patient characteristics, prevalence of concomitant conditions and hospitalization incidence in patients with AI compared to a...

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...

Background: Following the 34-week, double-blind, placebo-controlled main phase of REAL-1 (NCT02229851), this open-label trial extension evaluated efficacy and safety of somapacitan in patients aged 23–79 years with AGHD, for an additional 52 weeks (8 weeks’ dose titration followed by 44 weeks’ fixed dose treatment; 86 weeks’ treatment in total).Methods: Patients completing the main trial entered the extension: 1) somapacitan-treated p...

Introduction: In two Phase III studies (LINC3, NCT02180217; LINC4, NCT02697734), osilodrostat, (potent oral 11β-hydroxylase inhibitor), provided rapid, sustained reductions in mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC), alongside improvements in clinical signs of hypercortisolism and health-related quality of life (HRQoL), in Cushing’s disease (CD) patients. mUFC and LNSC are recommended for monitoring treatment response. We assessed wh...

Introduction: Phase II (LINC2, NCT01331239) and Phase III (LINC3, NCT02180217; LINC4, NCT02697734) studies showed that osilodrostat, a potent oral 11β-hydroxylase inhibitor, was an effective long-term treatment for Cushing’s disease patients. In this LINC programme pooled analysis, we examined how dose uptitration and adjustments during long-term maintenance can provide rapid, sustained mean urinary free cortisol (mUFC) control, and minimise AEs.<p class="abstext...

Background: Cushing’s syndrome (CS) has numerous comorbidities, including diabetes mellitus (DM). Levoketoconazole is a ketoconazole stereoisomer in clinical trials for treatment of CS.Methods: SONICS is a prospective, open-label, phase 3 maintenance-of-benefit study in adults with confirmed CS and mean urinary free cortisol (mUFC) of ≥1.5x upper limit of normal (ULN). Repeated hospitalization due to hyperglycemia or any complication related t...

Background: In a large 12-month Phase III study, pasireotide led to rapid and sustained decreases in UFC and provided clinical benefit in patients with Cushing’s disease. Here, we report data following an open-label, open-ended extension.Methods: 162 patients with persistent/recurrent or de novo Cushing’s disease were randomized in the core study. 58 patients with mean UFC≤ULN or clinical benefit at month 12 entered the extension...

Introduction: LNSC has shown high sensitivity and specificity for the initial diagnosis of CD and detection of disease recurrence; however, the use of LNSC to monitor medical treatment of CD is not well established. The results of an exploratory analysis evaluating changes in LNSC in CD patients receiving long-acting pasireotide during a Phase III study (CSOM230G2304; Lacroix et al. Lancet Diabetes Endocrinol 2018) are reported here.Methods: Pat...

Introduction: Osilodrostat (oral 11β-hydroxylase inhibitor) demonstrated rapid, sustained cortisol normalisation in Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734) in patients with Cushing’s disease (CD). Relative osilodrostat bioavailability is ~20% higher in Asian patients than other ethnicities; body weight is not a major determinant of this difference. This analysis of LINC 3 and LINC 4 evaluated osilodrostat efficacy and safety in Asian and non-Asia...