product are ~5-times higher than those for EllaOne based on AUC (human AUC0-24 h after a single 30 mg dose, 0.556 and 6 times higher based on body surface area. μg∙h/mL) Table 2. Estimated relative exposure to ulipristal acetate in selected toxicity studies. Species Study Dose AUC0–24 Exposure duration h mg/kg/day mg/m2/day AUC BSA Pivotal repeat dose toxicity Rat 6 months 1 6 1.8 – – (SD) 5 30 3.65 34 9 25 150 29.8 276 45 Monkey 6 months; 1 12 3.6 – – 9 months 5 60 0.026* 0.24 18 25 300 0.511* 4.7 91 Carcinogenicity (NOELs) Mouse 26 130 390 67.8 628 118 (TgRasH2) weeks Rat 2 years 10 60 14.6 135 18 (SD) Reproductive toxicity Rat Male 10 60 18 – – (SD) fertility 0.1 0.6 0.18 – – 0.3 1.8 0.5 – – 1 6 1.8 – – 0.03 0.18 0.05 – – 0.1 0.6 0.004 0.04 0.18 0.3 1.8 0.023 0.21 0.5 Rabbit 0.1 1.2 0.36 – – (NZW) 0.3 3.6 1.1 – – 1 12 3.6 – – 6 48 15 – –
product are ~5-times higher than those for EllaOne based on AUC (human AUC0-24 h after a single 30 mg dose, 0.556 μg∙h/mL) and 6 times higher based on body surface area. Table 2. Estimated relative exposure to ulipristal acetate in selected toxicity studies. Species Study duration Dose AUC0–24 h Exposure mg/kg/day mg/m2/day AUC BSA Pivotal repeat dose toxicity Rat (SD) 6 months 1 6 – – 1.8 5 30 3.65 34 9 25 150 29.8 276 45 Monkey 6 months; 9 months 1 12 – – 3.6 5 60 0.026* 0.24 18 25 300 0.511* 4.7 91 Carcinogenicity (NOELs) Mouse (TgRasH2) 26 weeks 130 390 67.8 628 118 Rat (SD) 2 years 10 60 14.6 135 18 Reproductive toxicity Rat (SD) Male fertility 10 60 – – 18 0.1 0.6 – – 0.18 0.3 1.8 – – 0.5 1 6 – – 1.8 0.03 0.18 – – 0.05 0.1 0.6 0.004 0.04 0.18 0.3 1.8 0.023 0.21 0.5 Rabbit (NZW) 0.1 1.2 – – 0.36 0.3 3.6 – – 1.1 1 12 – – 3.6 6 48 – – 15