Endocrine Abstracts

Introduction: A 24-week, PhIII, randomised study (PAOLA) demonstrated superior efficacy of pasireotide long-acting release (PAS-LAR; 40 and 60 mg) vs continued treatment with octreotide LAR 30 mg or lanreotide Autogel 120 mg (15.4%, 20.0% vs 0%) at providing biochemical control (GH<2.5 μg/l and normalized IGF-1) in patients with acromegaly inadequately controlled on first-generation somatostatin analogues. Results from PK/PD analyses of PAS-LAR are reported here.<...

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 ...

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...

Introduction: A recent 12-month randomized, double-blind study showed that pasireotide LAR was superior to octreotide LAR at providing biochemical control (GH and IGF1) in medically naïve patients with acromegaly. This analysis evaluates the PK/PD of pasireotide and octreotide in these patients.Methods: Patients received pasireotide LAR 40 mg/28 day (n=176) or octreotide LAR 20 mg/28 day (n=182) for 12 m. The relationship between p...

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...

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...