The doses of the AKR1C3 inhibitor BAY1128688 tested in this trial reached the anticipated plasma exposure range and the pharmacodynamics (such as increased androsterone) in the patients with endometriosis were comparable with those observed in healthy volunteers over a period of 4 weeks.

Dose-/exposure-dependent hepatotoxicity was observed following treatment with the AKR1C3 inhibitor BAY1128688 with characteristic clustering around the 12-week time point, although no hepatotoxicity had been observed in animal toxicology studies.

The absence of predictivity by the animal toxicology studies and by the short-term clinical studies in healthy volunteers in identifying potential effects in the human liver emphasizes the additional value of in vitro mechanistic and transporter interaction studies for the assessment of risk of hepatoxicity with continuous treatment (such as bile acid transporter interactions).