A 39-week oral toxicity study of ulipristal acetate in cynomolgus monkeys

Ulipristal acetate (UPA) is a novel Progesterone Receptor Modulator (PRM) and registered for the pre-operative treatment of symptomatic uterine fibroids during 3 months. In a study which assessed the potential toxicity of UPA in female cynomolgus monkeys following daily oral administration of 1, 5, or 25 mg/kg for 39 weeks, UPA was well tolerated with dose-dependent macroscopic and microscopic observations limited to the uterus and oviducts. These findings were considered to be related to the pharmacological action of UPA and showed evidence of partial reversibility. Findings in the endometrium were similar to PRM-associated-endometrial-changes (PAEC) described in PRM-treated women. No adverse effects were found that would raise concerns about potential pre-malignancy. Although the translation of these findings to human is limited by the small study size and species differences, these results from animals chronically exposed to up to 150 times the clinical UPA exposure are considered significant and supportive to the chronic administration of UPA for more than 3 months in women of reproductive age.