Phase 1 Study of Paltusotine, a Novel Oral Once‑Daily, Nonpeptide Selective Somatostatin Receptor 2 Agonist, in Healthy Japanese Adults.

Paltusotine is a novel, nonpeptide, once-daily oral, selective somatostatin 2 receptor (SST2) agonist. We evaluated the pharmacokinetics, pharmacodynamics, and safety of oral paltusotine in healthy Japanese adults in single‑dose (20, 40, 60, 80 mg) and repeated‑dose (40 mg once daily for 7 days in a two-sequence, two‑period crossover design) studies. In addition, the effects of food intake and pharmacodynamics were examined in the repeated-dose study. Eight participants were enrolled in each dose of the single-dose study, and 12 participants were enrolled in the repeated-dose study. In both studies, there were no deaths, serious adverse events, or severe adverse events. In the single-dose study, plasma paltusotine exposures increased in a dose-dependent manner for the dose range of 20 to 80 mg (based on Cmax and AUC0-∞), and the elimination half-life (t1/2) was 24-28 h. In the repeated-dose study, similar reductions from baseline in serum insulin-like growth factor-1 (IGF-I) were observed for 1-h pre-prandial (-60.1 ± 26.0 ng/mL) and 3-h post-prandial administration (-61.6 ± 17.7 ng/mL) on Day 7. Overall, this study establishes the pharmacokinetics, pharmacodynamics, and safety in healthy Japanese adults to support the development of paltusotine as a treatment for acromegaly and pituitary gigantism.