Safety Evaluation of KP-10 (Metastin 45–54) Following once Daily Intravenous Administration for 14 Days in Dog

Abstract

Kisspeptin-10 (previously referred as metastin 45–54), an active fragment of the endogenous full-length kisspeptin-145, is a potential therapeutic agent for reproductive disorders such as infertility, amenorrhea, and pubertal delay. A safety evaluation of KP-10 was conducted in dogs at the doses of 30, 100, and 1,000 μg/kg, given once daily intravenously for 14 days with a 14-day recovery period. There were no overt signs of drug-related toxicity observed in clinical signs, body weights, food consumption, clinical pathology, histopathology, urinalysis, electrocardiogram, or respiratory rate. Due to very rapid clearance of the peptide, luteinizing hormone (LH) levels were measured as a surrogate marker to demonstrate KP-10 exposure. The LH response reached a maximum concentration at 5 minutes post-dose and remained relatively unchanged for at least 30 minutes after dosing with no gender effect. LH concentrations on Day 1 were generally greater than on day 14. Vaginal cytology results indicated all dogs were in anestrous throughout the dosing period. There were also no KP-10–related findings observed in recovery animals on Day 29. In conclusion, KP-10 demonstrated favorable safety profile in dog where 1,000 μg/kg dose was considered as a no-observed-adverse-effect level dose when administered IV once daily for 14 days.