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

Endocrine Abstracts (2016) 41 EP699 | DOI: 10.1530/endoabs.41.EP699

A placebo-controlled study of repeated subcutaneous doses of COR-005 alone or with octreotide on GHRH-stimulated GH and pharmacokinetics in healthy male subjects

Klaus Kutz1, Manuel Haschke2, Christoph Beglinger2, Jiří Liška3, Carsten Dehning4 & Fredric Cohen5

1AccelPharm, Basel, Switzerland; 2University Hospital Basel, Basel, Switzerland; 3CEPHA sro, Pilsen, Czech Republic; 4Aspireo Pharmaceuticals Ltd, Tel Aviv, Israel; 5Strongbridge Biopharmaceuticals plc, Trevose, PA, USA.

Octreotide is first-line medical therapy for patients with acromegaly. Up to 80% of patients are not satisfactorily controlled on octreotide alone and up to 20% have no response. COR-005 (previously DG3173) is a novel somatostatin analogue under investigation for treatment of acromegaly. COR-005 has high affinity for human somatostatin receptor subtypes 2, 4 and 5.

The study was designed to assess pharmacokinetics of escalating doses COR-005 sc tid and compare the pharmacodynamics of COR-005 alone or in combination with octreotide 300 μg sc tid for 6.3 days versus octreotide 300 μg sc tid alone and placebo on GHRH-stimulated GH profiles.

A total of 42 subjects (6 total per group) received placebo (P, N=1/gp), octreotide 300 μg tid (O, N=1/gp) or COR-005 alone (C, N=4/gp) as 100 μg, 300 μg, 900 μg, or 1800 μg C tid or as 100 μg or 300 μg or 900 μg C in combination with O. GHRH stimulation was performed before first and after four treatments.

Maximal inhibition of GHRH-stimulated GH by COR-005 or octreotide alone was ranked as follows: P < (100 μg C or 300 μg C) < (900 μg C or O) <1800 μg C. GH inhibition with combinations of COR-005 and O were in the order of: O < (O+100 μg C and O+300 μg C) < O+900 μg C. COR-005 Tmax was ≤1 hour and t1/2 was ~2 h after first and last injections. Cmax and AUC0-8 increased dose-linearly. Co-administration of COR-005 with O did not affect C PK below 900 μg, greater variability in C AUC0-8 was noted at 900 μg.

COR-005 inhibits dose-dependently GHRH-stimulated GH with less potency but similar maximal efficacy as maximally dosed octreotide.

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