2019 年 6 巻 7 号 p. 269-275
TTA-121 is a novel oxytocin nasal spray with high bioavailability and is expected to increase oxytocin delivery to the brain by adjusting osmolality and viscosity of the formulation. As nonclinical safety studies to support the conduct of the Phase 1 and Phase 2 studies of TTA-121, a 6-week repeated intranasal dose toxicity study of TTA-121 in monkeys was conducted. In the present study, TTA-121 was administered intranasally to male and female cynomolgus monkeys once daily for 6 weeks at 0, 26.88, 134.4, and 672.0 U/body/day followed by a 4-week recovery period to investigate the toxicity of oxytocin and systemic exposure to oxytocin. No animal died or was euthanized due to moribundity. There were no test article-related changes in clinical signs, body weight, food consumption, ophthalmology, electrocardiography, urinalysis, hematology, blood chemistry, necropsy, organ weights, or histopathology at any dose level during the dosing or recovery periods. The toxicokinetic analysis indicated that systemic exposures of oxytocin increased with the dose ranging from 26.88 to 672.0 U/body/day on the first and final day of dosing. Based on these results, the no-observed adverse effect level (NOAEL) of TTA-121 was 672.0 U/body/day.
