Pharmacokinetics and Safety of LY03010, a Novel Monthly Intramuscular Injectable Extended-release Paliperidone Palmitate Suspension in Patients with Schizophrenia or Schizoaffective Disorder

Abstract: LY03010 (paliperidone palmitate) is in development as a pharmaceutical equivalent drug product to the listed drug (LD), INVEGA SUSTENNA® for schizophrenia and schizoaffective disorders with an alternative initial dosing regimen (IDR). Opposed to two weekly injections for the initiation doses of LD, LY03010 is given once a month consistently from initiation. This multicenter, randomized, open-label, relative bioavailability study established the bioequivalence (BE) of LY03010 and LD at steady state and comparatively evaluated the pharmacokinetics (PK) of paliperidone during the IDRs (Days 1 to 28 for LY03010 and Days 1 to 35 for LD). A total of 281 adult patients were randomized (1:1) to receive 6 intramuscular (IM) injections of LY03010 (351 mg on Day 1 and 156 mg monthly thereafter) or 7 IM injections of LD (Days 1 [234 mg], 8 [156 mg], and 156 mg monthly thereafter). The 90% confidence intervals (CIs) for the geometric least squares means ratios (GLSMRs) (LY03010:LD) for paliperidone Cmax and AUCtau at steady state were within the BE limits (80% to 125%). After the initial injection of 351 mg LY03010, a therapeutic level of paliperidone was reached rapidly without oral supplementation. The total exposure (AUC0-28d and AUC0-35d) to paliperidone during the IDR was comparable for the two treatments. The safety/tolerability profiles were similar for LY03010 and LD. Overall, LY03010 displayed a simplified dosing regimen compared with that for INVEGA SUSTENNA, which may improve treatment compliance. LY03010 was well tolerated.Short Description: This bioequivalence study evaluated the pharmacokinetics and safety of LY03010, a monthly intramuscular paliperidone palmitate injectable in development for the treatment of schizophrenia and schizoaffective disorder. Patients received initiation dosing (1 dose of LY03010 or 2 doses of LD) and 5 monthly maintenance doses of LY03010 or LD. Bioequivalence between LY03010 and LD at steady state was established. Comparable therapeutic levels of paliperidone were observed during the IDRs of both drugs. LY03010 was well tolerated.Name of Sponsoring Organization(s): Geneora Pharma (Shijiazhuang) Co., Ltd.