Dose selection for paltusotine, a once daily oral nonpeptide, somatostatin receptor 2 ligand, for the treatment of patients with Carcinoid Syndrome (CS)

#3380

Introduction: Long-acting somatostatin receptor ligands (LA-SRLs) are first line therapy for neuroendocrine tumor (NET) syndromes including acromegaly and the carcinoid syndrome (CS). In acromegaly, two phase 2 studies (NCT 03789656 and 03792555) suggested that patients injected with SRLs can switch to once daily orally bioavailable paltusotine (CRN00808), a nonpeptide, small molecule, somatostatin type 2 (SST2) receptor ligand (SRL), while maintaining stable serum IGF-1 levels. However, CS patients may require higher doses of an orally administered drug due to maldigestion commonly associated with the syndrome or its treatment and the pharmacokinetics (clearance and volume of distribution) of paltusotine may differ between CS and acromegaly because of differences in metabolic capacity of the liver and body composition.

Aim(s): To design a PK/PD study evaluating the use of once daily oral paltusotine to control symptoms and inhibit functional tumor markers in patients with CS.

Materials and methods: We analysed data from the capsule formulation used in the acromegaly patient studies to determine dose- and exposure-response and from a new tablet formulation evaluated in healthy volunteers.

Conference:

Presenting Author:

Authors: Lagast H, Madan A, Metz D, Luo R, Struthers S,

Keywords: neuroendocrine tumor, carcinoid syndrome, paltusotine, somatostatine receptor ligand, dose-response, exposure-response,