Phase 1 positron emission tomography (PET) study of the receptor occupancy of rolapitant, a novel NK-1 receptor antagonist.

e20690 Background: Rolapitant is a potent, highly selective, competitive and long acting NK-1 receptor antagonist in development for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetogenic chemotherapy. NK-1 receptor occupancy (RO) is a critical predictor of delayed efficacy in CINV; therefore, this PET study determined the levels and duration of RO achieved by rolapitant using 11C-GR205171, a radiolabeled tracer NK-1 ligand. Methods: 14 healthy subjects were enrolled into this open-label, single-dose, pharmacodynamic, dose-escalation phase 1 study. Baseline PET scans with the radiotracer 11C-GR205171 alone followed by repeat PET scans 120 hours post administration of rolapitant were performed. Blood samples were collected up to 120 hours following rolapitant administration to determine rolapitant plasma concentration. The Patlak method was used to assess the baseline (uptake of 11C-GR205171) for the regions of interest. Regional occupancies (%) ...