Poster
94
(#94) Population pharmacokinetics and dosing simulations for alternative maintenance doses of 351 mg LY03010 (paliperidone palmitate) in patients with schizophrenia or schizoaffective disorder
Psych Congress 2025
Abstract: LY03010 (brand name ERZOFRI®) is a newly approved once-a-month paliperidone palmitate (PP1M) extended-release injectable suspension with a differentiated single initial injection of 351 mg followed by a consistent monthly maintenance dosing regimen. The objective of the population pharmacokinetic (popPK) analyses was to investigate the drug exposure of paliperidone at steady state after administering 351 mg LY03010 as a maintenance dose using different dosing intervals.
Using Nonlinear Mixed Effects Modeling (NONMEM), a popPK model was developed and successfully characterized the paliperidone PK data obtained from two Phase 1 studies of LY03010. Model-based simulations were then conducted and summarized. Paliperidone plasma concentration-time profiles using 351 mg paliperidone palmitate as a maintenance dose at dosing intervals of once every 6 weeks (Q6W) or once every 8 weeks (Q8W) were compared to those from the approved recommended monthly maintenance dosing regimens for PP1M. Simulated plasma concentration-time profiles of the dosing regimens indicated that administration of 351 mg paliperidone palmitate Q6W provided similar drug exposure to 234 mg PP1M every 4 weeks (Q4W) at steady state. Simulation of 351 mg paliperidone palmitate Q8W showed that Cmax,ss of paliperidone fell in-between that of maintenance dose at 234 mg Q4W and 156 mg Q4W while Ctrough,ss was comparable to that of the monthly maintenance dose at 117 mg PP1M.
PopPK analyses provided simulated data of alternative dosing regimens using LY03010 351 mg.
Short Description: PopPK simulation analyses evaluated paliperidone exposure using 351 mg paliperidone palmitate (PP) extended-release injectable suspension at different dosing intervals compared to the approved recommended monthly maintenance dosing regimens for PP1M. Simulation results suggested that 351 mg PP Q6W could provide similar drug exposure to 234 mg PP1M Q4W at steady state. 351 mg PP Q8W showed comparable Ctrough,ss to that of 117 mg PP1M Q4W.
Name of Sponsoring Organization(s): Luye Innomind Pharma Shijiazhuang Co., Ltd.
Using Nonlinear Mixed Effects Modeling (NONMEM), a popPK model was developed and successfully characterized the paliperidone PK data obtained from two Phase 1 studies of LY03010. Model-based simulations were then conducted and summarized. Paliperidone plasma concentration-time profiles using 351 mg paliperidone palmitate as a maintenance dose at dosing intervals of once every 6 weeks (Q6W) or once every 8 weeks (Q8W) were compared to those from the approved recommended monthly maintenance dosing regimens for PP1M. Simulated plasma concentration-time profiles of the dosing regimens indicated that administration of 351 mg paliperidone palmitate Q6W provided similar drug exposure to 234 mg PP1M every 4 weeks (Q4W) at steady state. Simulation of 351 mg paliperidone palmitate Q8W showed that Cmax,ss of paliperidone fell in-between that of maintenance dose at 234 mg Q4W and 156 mg Q4W while Ctrough,ss was comparable to that of the monthly maintenance dose at 117 mg PP1M.
PopPK analyses provided simulated data of alternative dosing regimens using LY03010 351 mg.
Short Description: PopPK simulation analyses evaluated paliperidone exposure using 351 mg paliperidone palmitate (PP) extended-release injectable suspension at different dosing intervals compared to the approved recommended monthly maintenance dosing regimens for PP1M. Simulation results suggested that 351 mg PP Q6W could provide similar drug exposure to 234 mg PP1M Q4W at steady state. 351 mg PP Q8W showed comparable Ctrough,ss to that of 117 mg PP1M Q4W.
Name of Sponsoring Organization(s): Luye Innomind Pharma Shijiazhuang Co., Ltd.
