Poster
86
(#86) Population pharmacokinetic simulation for 351 mg LY03010 (paliperidone palmitate) administered every 4 weeks in patients with schizophrenia or schizoaffective disorder
Psych Congress 2025
Abstract: Once-a-month paliperidone palmitate (PP1M) long-acting injectables are effective for schizophrenia and schizoaffective disorder. In practice, higher-than-recommended maintenance doses or shorter-than-recommended dosing intervals of paliperidone palmitate (PP) are sometimes used to achieve drug exposure exceeding the recommended dosing regimens, especially in patients with inadequate response to the maximum approved doses and intervals. Study reports showed that higher paliperidone plasma concentrations than the recommended maximum maintenance dose regimen of 234 mg every 4 weeks (Q4W) might result in improved clinical outcomes with minimal side effects in some patients.
The highest available dose of PP1M is 351 mg (LY03010 [brand name ERZOFRI®]), which is approved as a single initiation injection followed by recommended monthly maintenance doses up to 234 mg. Model-based population pharmacokinetic (popPK) simulations were conducted to compare the steady state drug exposure of paliperidone achieved by maintenance doses of 351 mg PP Q4W or from 234 mg PP every 3 weeks (Q3W). A popPK model was developed using Nonlinear Mixed Effects Modeling (NONMEM) with the PK data from two Phase 1 studies of LY03010. Simulated data showed that 351 mg PP Q4W produced steady state paliperidone exposure comparable to 234 mg Q3W based on analysis of Cmax_ss and Ctrough_ss.
PopPK simulation analyses imply that 351 mg PP Q4W may provide an alternative option to 234 mg Q3W when treating patients with schizophrenia or schizoaffective disorder exhibiting inadequate response to 234 mg Q4W. There is no clinical data to support this alternative dosing regimen. Caution is warranted for off-label use of PP.
Short Description: PopPK simulation analyses evaluated the drug exposure of paliperidone with 351 mg paliperidone palmitate extended-release injectable suspension used as a maintenance dose every 4 weeks compared to a maintenance dose of 234 mg paliperidone palmitate every 3 weeks. Simulated data demonstrated that these two regimens were comparable at steady state.
Name of Sponsoring Organization(s): Luye Innomind Pharma Shijiazhuang Co., Ltd.
The highest available dose of PP1M is 351 mg (LY03010 [brand name ERZOFRI®]), which is approved as a single initiation injection followed by recommended monthly maintenance doses up to 234 mg. Model-based population pharmacokinetic (popPK) simulations were conducted to compare the steady state drug exposure of paliperidone achieved by maintenance doses of 351 mg PP Q4W or from 234 mg PP every 3 weeks (Q3W). A popPK model was developed using Nonlinear Mixed Effects Modeling (NONMEM) with the PK data from two Phase 1 studies of LY03010. Simulated data showed that 351 mg PP Q4W produced steady state paliperidone exposure comparable to 234 mg Q3W based on analysis of Cmax_ss and Ctrough_ss.
PopPK simulation analyses imply that 351 mg PP Q4W may provide an alternative option to 234 mg Q3W when treating patients with schizophrenia or schizoaffective disorder exhibiting inadequate response to 234 mg Q4W. There is no clinical data to support this alternative dosing regimen. Caution is warranted for off-label use of PP.
Short Description: PopPK simulation analyses evaluated the drug exposure of paliperidone with 351 mg paliperidone palmitate extended-release injectable suspension used as a maintenance dose every 4 weeks compared to a maintenance dose of 234 mg paliperidone palmitate every 3 weeks. Simulated data demonstrated that these two regimens were comparable at steady state.
Name of Sponsoring Organization(s): Luye Innomind Pharma Shijiazhuang Co., Ltd.
