Endocrine Abstracts

Introduction: Osilodrostat is a potent oral 11β-hydroxylase inhibitor currently in Phase III clinical development for the treatment of Cushing’s syndrome (CS). The key pharmacokinetic (PK) properties, drug–drug interactions (DDIs), and population PK findings for osilodrostat in humans are summarized.Methods: Osilodrostat PK has been characterized in nine Phase I studies (healthy subjects and subjects with hepatic or renal impairment), two ...

Background: Pasireotide is available in twice-daily subcutaneous (sc) and long-acting intramuscular (im) formulations. Pasireotide sc depot is an investigational extended-release sc formulation designed for improved handling and administration. Results are reported from a Phase I dose-escalating study.Methods: All subjects received a single dose of pasireotide sc (600 μg) and were randomized 12:2:2 to pasireotide sc depot as a single upper-thigh inj...

Introduction: A monthly, long-acting formulation of pasireotide normalized or reduced mean urinary free cortisol (mUFC) in most patients with Cushing’s disease (CD) in a multicentre, double-blind, Phase III study. The effects of long-acting pasireotide on signs and symptoms of CD are reported here.Methods: Patients with persistent/recurrent (n=123) or de novo (non-surgical candidates; n=27) CD and mUFC≥1.5–5xULN...

Background: Octreotide s.c. depot is a novel, ready-to-use formulation administered via a thin needle, which may allow self-administration. In a phase 1 study in healthy volunteers, octreotide s.c. depot provided greater bioavailability with faster onset and greater IGF1 suppression than long-acting octreotide. Here, we present data from a phase 2 study evaluating pharmacokinetics (PK), efficacy, safety, and tolerability of octreotide s.c. depot in patients with acromegaly and...

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: Long-acting pasireotide reduced urinary free cortisol (UFC) in most patients with Cushing’s disease (CD) during a large Phase III study (Lacroix et al. Lancet Diabetes Endocrinol 2018). The analyses presented here explored the impact of baseline characteristics on response to long-acting pasireotide.Methods: 150 patients with persistent, recurrent or de novo CD and mean UFC (mUFC; from three 24-hour samples collected ...

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: The 12-month results of a multicentre, double-blind, Phase III study showing the efficacy and safety of a monthly, long-acting formulation of pasireotide in Cushing’s disease (CD) patients have been reported previously (Lacroix et al. Lancet Diabetes Endocrinol 2018). The results of the extension phase of this study are reported here.Methods: Patients (n=150) with persistent/recurrent or de novo CD and mean u...