Preclinical and Toxicology Studies of LPM7100328, a Novel Oral GnRH Antagonist.

LPM7100328 is a novel oral GnRH antagonist being developed for the prevention of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian stimulation. The studies presented herein reported assessment of safety in favor of human clinical trials. Safety pharmacology studies showed that LPM7100328 had no adverse pharmacological effects. No apparent abnormalities were observed in 28-day rat and dog toxicity study, the no observed adverse effect level (NOAEL) was 100 mg/kg and 50 mg/kg, respectively. LPM7100328 was found to be non-genotoxic in the Ames, aberration test or micronucleus assay. In the rat fertility and early embryonic development study and rabbit fertility and embryo-fetal development study, LPM7100328 demonstrated a generally favorable safety profile, with no teratogenic effects observed in either species. And LPM7100328 showed no phototoxicity. Collectively, these findings indicate a favorable nonclinical safety profile for LPM7100328 in the prevention of premature LH surges during women undergoing controlled ovarian stimulation.