Atebrioz (zilurgisertib)

Each cohort enrolled 18 healthy adults and used an open-label, fixed-sequence design in which zilurgisertib 100 mg was given alone and then with itraconazole or rifampin, so each participant served as their own control rather than being randomized to a comparator arm. The study tested a single zilurgisertib dose of 100 mg, one-fifth of the highest dose evaluated in earlier phase 1 studies, together with a single regimen of one strong CYP3A4 inhibitor (itraconazole 200 mg once daily) and one strong CYP3A4 inducer (rifampin 600 mg once daily); the label's statements on moderate CYP3A4 inhibitors, moderate CYP3A4 inducers, and CYP2D6 inhibitors remain model predictions rather than results of a clinical study, and the full-text discussion notes that more potent strong CYP3A4 inhibitors than itraconazole could produce a larger increase in zilurgisertib exposure than observed here. Sample size for each cohort was set empirically, following precedent from similar studies, rather than by a statistical power calculation, and two participants in the rifampin cohort discontinued before the second treatment period and were replaced. The study enrolled healthy adults rather than participants with fibrodysplasia ossificans progressiva, and the reason for the variability in interaction magnitude observed across participants was not determined. The cardiac safety publication cites a 2.5-fold increase in AUC under strong CYP3A inhibition, which differs from the 2.13-fold increase in AUC0-inf reported by this study and by the label.