OR23-05 Human Absorption Metabolism Excretion and Absolute Oral Bioavailability of 14C-CRN00808 an Orally Bioavailable Nonpeptide Selective Somatostatin Receptor 2 (sST2) Biased Agonist for the Treatment of Acromegaly

摘要

Injected depot formulations of somatostatin peptide analogs are routinely used to treat acromegaly and neuroendocrine tumors (NETs). {"type":"entrez-protein","attrs":{"text":"CRN00808","term_id":"1048626668","term_text":"CRN00808"}}CRN00808, a small molecule nonpeptide selective somatostatin receptor 2 (sst2) agonist, is being evaluated for efficacy and safety in patients with acromegaly. The current Phase 1 study was conducted in two Parts: In Part A, the absorption, metabolism, excretion, and mass balance of a single oral dose of 20 mg [14C]-{"type":"entrez-protein","attrs":{"text":"CRN00808","term_id":"1048626668","term_text":"CRN00808"}}CRN00808 (3.0 MBq) oral solution was characterized in six healthy male subjects. Plasma, blood, urine, and feces were collected for up to 432 hours, and were analyzed for total radioactivity and {"type":"entrez-protein","attrs":{"text":"CRN00808","term_id":"1048626668","term_text":"CRN00808"}}CRN00808 concentrations (plasma only). Metabolite profiling was conducted on the plasma, urine, and feces samples. In Part B, the absolute bioavailability of {"type":"entrez-protein","attrs":{"text":"CRN00808","term_id":"1048626668","term_text":"CRN00808"}}CRN00808 was determined by administering a single oral dose of 20 mg {"type":"entrez-protein","attrs":{"text":"CRN00808","term_id":"1048626668","term_text":"CRN00808"}}CRN00808 compared with a single micro-tracer intravenous (IV) bolus injection of 50 µg [14C]-{"type":"entrez-protein","attrs":{"text":"CRN00808","term_id":"1048626668","term_text":"CRN00808"}}CRN00808 (0.0185 MBq) in five healthy male subjects. The IV dose was administered approximately 90 minutes after the oral dose. Plasma samples were collected for up to 144 hours and were analyzed for total radioactivity and {"type":"entrez-protein","attrs":{"text":"CRN00808","term_id":"1048626668","term_text":"CRN00808"}}CRN00808 concentrations (plasma only).