Population pharmacokinetic modeling and simulation to guide dose selection for RBP-7000, a new sustained-release formulation of risperidone

RBP‐7000 is a long‐acting formulation of risperidone designed for once‐monthly subcutaneous injection for the treatment of schizophrenia. The objective was to estimate clinically effective doses of RBP‐7000 based on model simulations and on the comparison with other long‐acting injectable antipsychotics. A population pharmacokinetic model of RBP‐7000 was developed in 90 clinically stable schizophrenic patients having received single/repeated doses of 60, 90, or 120 mg. Model simulations were conducted to compare active moiety plasma exposure after repeated RBP‐7000 administrations to the published data of long‐acting risperidone injection (Risperdal® Consta®) at 25 and 50 mg, and of paliperidone palmitate (Invega® Sustenna®) at 50 and 100 mg equivalent paliperidone. Predictions of dopamine D2 receptor occupancy were derived from the simulated active moiety concentrations. Simulations showed similar active moiety plasma exposure at steady‐state for 90 mg of RBP‐7000 and 25 mg of long‐acting risperidone. In comparison to risperidone, RBP‐7000 reached effective concentrations immediately after the first administration. RBP‐7000 at the doses of 60 and 90 mg provided similar active moiety plasma concentrations at steady‐state compared to 50 and 100 mg equivalent paliperidone, respectively. These findings provide guidance for dose selection in Phase III clinical trials and suggest potential benefits for RBP‐7000 over competitors.