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

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 the 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.