Rolapitant for Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Patients With Breast Cancer

Single Ascending Dose Pharmacokinetics of Rolapitant Administered Intravenously at Supratherapeutic Doses in Healthy Volunteers A 2-part, open-label, single-ascending dose study was performed to evaluate the safety and tolerability of IV rolapitant at supratherapeutic doses in healthy volunteers (Abstract 0489). In part 1, 36 healthy subjects received a 30-minute infusion of rolapitant (202.5 mg to 270 mg). In part 2, 64 subjects received a single 30-minute infusion of rolapitant (270 mg) for further safety evaluation. Based on AUC analysis, the plasma concentration of rolapitant increased proportionately across the dose range. C-max appeared to increase proportionately with the dose, with some variation seen at dose 247.5 mg. In subjects who received the 270 mg dose, the mean C-max was approximately 3500 ng/mL to 3700 ng/mL, demonstrating a C-max similar to that observed in prior studies of subjects who received oral rolapitant (720 mg). The mean half-life of IV rolapitant ranged from 135 hours to 155 hours, which was consistent with results from oral rolapitant. The pharmacokinetics of the rolapitant metabolite, M19, were also similar to those observed with the oral formulation of the drug. There were no serious AEs or severe treatment-emergent AEs related to the study drug.