An Open-Label Dose-Escalation Study of Once-Daily and Twice-Daily Pasireotide in Healthy Volunteers: Safety, Tolerability, and Effects on Glucose, Insulin, and Glucagon Levels

作者：Shenouda Magdy^*; Maldonado Mario; Wang Yanfeng; Bouillaud Emmanuel; Hudson Michelle; Nesheiwat Dalal; Hu Ke

来源：American Journal of Therapeutics, 2014, 21(3): 164-173.

DOI：10.1097/MJT.0b013e31824c3eb4

• pasireotide
• SOM230
• hyperglycemia
• insulin
• safety

Pasireotide is a multireceptor-targeted somatostatin analogue that has high affinity for 4 of the 5 somatostatin receptor subtypes (sst(1,2,3) and sst(5)) and has therapeutic potential in conditions with tumors of neuroendocrine origin, such as Cushing disease, acromegaly, and neuroendocrine tumors. This phase 1, open-label, dose-escalation study assessed the overall safety and tolerability of once-daily and twice-daily pasireotide and its effects on glucose, insulin, and glucagon levels in healthy volunteers. Eleven cohorts (n = 6 for each) received subcutaneous pasireotide 150, 300, 600, 900, 1200, or 1500 g once daily, or 150, 300, 450, 600, or 750 g twice daily, for 8 days. Pasireotide was generally well tolerated at all doses; adverse events were predominantly mild-to-moderate gastrointestinal disorders. All participants experienced fasting and postprandial plasma glucose elevations after all doses of pasireotide; increases in blood glucose level seemed to be dose dependent. Hyperglycemia was associated with a marked suppression of insulin secretion and a mild inhibition of glucagon secretion. In conclusion, pasireotide showed good overall tolerability at doses up to 1500 g once daily and 750 g twice daily for 8 days. Both fasting and postprandial hyperglycemia occurred after all doses of pasireotide, which was related to the suppression of insulin secretion.

• 出版日期2014-6