title: Pasireotide (SOM230), a novel multireceptor-targeted somatostatin analogue, is well tolerated when administered as a continuous 7-day subcutaneous infusion in healthy male volunteers.
abstract: Pasireotide is a novel multireceptor-targeted somatostatin analogue that has shown efficacy in patients with acromegaly and Cushing's disease when administered by subcutaneous (SC) injection. This study assessed the safety, tolerability, and pharmacokinetics (PK) of a continuous infusion of pasireotide in healthy volunteers. In this single-center, open-label, dose escalation study, healthy male volunteers received a 7-day continuous SC infusion of pasireotide in sequential ascending-dose cohorts. Single and/or 8-hour blood samples were taken on days 1 to 10 to assess PK and on days 1, 2, and 7 and a control day to assess glucose metabolism. Adverse events were evaluated throughout. Forty-four participants were enrolled into 8 cohorts: pasireotide 450, 900, 1350, 1800 (3 cohorts were enrolled at this dose level), 2250, and 2025 µg/d. Doses were well tolerated up to 2025 µg/d. Adverse events were generally mild and gastrointestinal. Pasireotide steady-state clearance was reduced at high doses, and plasma concentrations increased disproportionately with increasing dose. Blood glucose levels increased after initiation of pasireotide infusion with attenuation by day 7. Insulin and glucagon levels decreased after pasireotide infusion, with insulin levels exhibiting a greater degree of suppression. Pasireotide has the potential to be administered as a long-acting release formulation, and future studies are warranted.
authors.affiliation: Division of Endocrinology, Medical Center, University of Duisburg-Essen, Essen, Germany. stephan.petersenn@endoc-med.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Petersenn
authors.forename: Nicole
authors.initials: N
authors.lastname: Unger
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
authors.forename: Brigitte
authors.initials: B
authors.lastname: Weisshaar
authors.forename: Yilong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bouillaud
authors.forename: Karina Hermosillo
authors.initials: KH
authors.lastname: Reséndiz
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Klaus
authors.initials: K
authors.lastname: Mann
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000097:blood; D006801:Humans; D055104:Infusions, Subcutaneous; D007328:Insulin / Q000097:blood; D008297:Male; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; C517782:pasireotide