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.

Pasireotide is a multireceptor-targeted somatostatin analogue that has high affinity for 4 of the 5 somatostatin receptor subtypes (sst1,2,3 and sst5) 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 μg once daily, or 150, 300, 450, 600, or 750 μg 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 μg once daily and 750 μg 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.