Context: A somatostatin-dopamine chimera (BIM23B065) was under investigation to reduce GH secretion for the treatment of pituitary adenomas.Objective: To determine pharmacokinetics, safety, and... Show moreContext: A somatostatin-dopamine chimera (BIM23B065) was under investigation to reduce GH secretion for the treatment of pituitary adenomas.Objective: To determine pharmacokinetics, safety, and tolerability and to monitor hormonal changes after single and multiple subcutaneous BIM23B065 administrations.Design: Randomized, double-blind, placebo-controlled, parallel-group design with five single and three 13-day multiple ascending-dose cohorts.Patients: A total of 63 healthy male white volunteers were enrolled (47 active, 16 placebo).Main Outcome Measures: Pharmacokinetics, GH, prolactin (PRL), IGF-1, GH after GHRH administration, and general clinical safety criteria.Results: The maximum dosage of BIM23B065 administered in this study was 1.5 mg. BIM23B065 reduced the mean GH concentrations after 8 and 13 days of treatment. A decrease in GH release after GHRH administration indicated inhibition of the hypothalamic-pituitary-somatotropic axis. IGF-1 was not altered after single doses but showed a significant change from baseline after multiple dosing. PRL secretion was reduced in all subjects who were treated. Orthostatic hypotension and injection site reactions were commonly observed at high dosages. A 6-day uptitration period was included to successfully lower the cardiovascular effects in the multiple ascending dose part of the study.Conclusions: Proof of pharmacology of BIM23B065 was shown by a reduction in GH, IGF-1, and PRL concentrations in healthy male volunteers, supporting activity of the somatostatin analog and dopamine agonist moieties. The safety and tolerability of the higher dosing regions was limited mainly by orthostatic hypotension. Show less
A somatostatin-dopamine chimera (BIM23B065) was under investigation to reduce growth hormone (GH) secretion for the treatment of pituitary adenomas.To determine the pharmacokinetics, safety,... Show moreA somatostatin-dopamine chimera (BIM23B065) was under investigation to reduce growth hormone (GH) secretion for the treatment of pituitary adenomas.To determine the pharmacokinetics, safety, tolerability, and to monitor hormonal changes after single and multiple subcutaneous BIM23B065 administrations.Randomized, double-blind, placebo-controlled, parallel-group design with five single and three 13-day multiple ascending dose cohorts.A total of 63 healthy male Caucasian volunteers were enrolled, 47 active, 16 placebo.Pharmacokinetics, GH, prolactin (PRL), insulin-like growth factor-1 (IGF-1), GH after GH releasing hormone (GHRH) administration, and general clinical safety criteria.The maximum dose administered of BIM23B065 in this study was 1.5 mg. BIM23B065 reduced the mean GH concentrations after 8 and 13 days of treatment. A decrease in GH release after GHRH administration indicated inhibition of the hypothalamus-pituitary-somatotropic axis. IGF-1 was not altered after single doses but showed a significant change from baseline after multiple dosing. The secretion of PRL was reduced in all treated subjects. Orthostatic hypotension and injection site reactions were commonly observed at high doses. A 6-day up-titration period was included to successfully lower the cardiovascular effects in the multiple ascending dose part of the study.Proof-of-pharmacology of BIM23B065 was shown by a reduction in GH, IGF-1 and PRL concentrations in healthy male volunteers, supportive for activity of the somatostatin analogue and dopamine agonist moieties. The safety and tolerability in the higher dosing regions was mainly limited by orthostatic hypotension.ContextObjectiveDesignPatientsMain Outcome MeasuresResultsConclusions Show less
