ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2016) 41 GP123 | DOI: 10.1530/endoabs.41.GP123

A placebo-controlled study to assess the dose-effect of COR-005, a novel somatostatin analogue on plasma glucose regulation compared to octreotide in healthy male subjects

Klaus Kutz1, Manuel Haschke2, Christoph Beglinger2, Carsten Dehning3 & Fredric Cohen4

1AccelPharm, Basel, Switzerland; 2University Hospital Basel, Basel, Switzerland; 3Aspireo Pharmaceuticals Ltd, Tel Aviv, Israel; 4Strongbridge Biopharmaceuticals plc, Trevose, PA, USA.

Somatostatin analogues (SSAs) approved to treat acromegaly tend to suppress postprandial insulin/glucagon secretion and can worsen glucose tolerance. COR-005, a novel SSA, is under investigation for treatment of acromegaly. In rodents, COR-005 effectively inhibits GH secretion with 10,000-fold greater potency compared with insulin release suppression. We sought to determine for the first time the effects of COR-005 on postprandial glucose in humans.

The pharmacodynamic effects of single subcutaneous doses of COR-005 300, 900, and 1800 μg, octreotide 300 μg and placebo on glucose, insulin and glucagon dynamics were investigated for 4 h after intake of a mixed meal in eight healthy male subjects using a randomized cross-over design.

Following COR-005 300 and 900 μg, there were slight increases in maximum blood glucose concentrations (9.76±1.00 and 9.73±1.31 vs 7.56±0.93 mmol/l) and in the 4-h blood glucose AUECGlucose compared to placebo (26.13±2.18, 28.86±3.82 vs 23.02±1.83 mmolxh/l). A higher increase was observed after injection of COR-005 1800 μg and the highest after octreotide 300 μg (AUECGlucose: 33.56±4.71 and 38.69±5.79 mmolxh/l). Octreotide significantly suppressed plasma insulin and glucagon secretion compared to placebo (AUECInsulin 15.56±2.02 vs 44.29±10.65 μUxh/ml and AUECGlucagon 135.5±55.1 vs 363.2±40.9 pgxh/ml) whereas COR-005 caused only a dose-dependent delay in insulin and glucagon secretion but had no significant effect on AUECInsulin or AUECGlucagon.

After intake of a mixed meal, COR-005 single doses up to 900 μg had no significant effect on total insulin and glucagon secretion compared to placebo and a marginal effect on blood glucose. COR-005 1800 μg less strongly inhibited postprandial insulin and glucagon compared to octreotide. COR-005 might offer a reduced risk of hyperglycemia relative to other SSAs currently used to treat acromegaly.

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