Abstract

A Comparative Pharmacokinetic Evaluation of Paliperidone Palmitate Extended-Release Injectable Suspensions: An Open Label, Randomized, Two treatment, Two-Period, Two-Sequence, Multiple Dose, Steady State Crossover Bioequivalence Study in Patients with Schizophrenia and/or Schizoaffective Disorder

Author(s): Arthik Shetty, Shruti Dharmadhikari, Chintan Khandhedia, Amey Mane, Prashant Devkare, Amaresh Chakra, Chirayu Shah

Background: Schizophrenia (SZ) and Schizoaffective (SA) disorders are severe psychiatric conditions affecting millions globally. Paliperidone, administered intramuscularly once a month is a long-acting injectable antipsychotic, effective in symptom control and relapse prevention. This study assessed bioequivalence and safety of paliperidone palmitate Extended-Release (ER) Injectable suspension (Paliris LA^®) (Test(T)) manufactured by Sun Pharmaceuticals Industries Limited compared to paliperidone palmitate ER Injectable suspension (Invega Sustenna^®) (Reference(R)) manufactured by Janssen Pharmaceuticals in patients with SZ and or SA disorder.

Methods: This open-label, multi-center, randomized, two-treatment, two-period, two-sequence, steady-state, cross-over, multiple-dose bioequivalence study enrolled 108 patients. Patients received 156 mg/ml of T or R on Day-1, Day-29, Day-57, Day-85 and Day-113 (Period-01), followed by other treatment on Day-141, Day-169, Day-197, Day-225 and Day-253 (Period-02), per randomization schedule. Pharmacokinetic parameters Maximum concentration at steady state (C_maxSS), Area under concentration-time curve (AUC_0-τ) AND mean plasma concentration-time profiles at steady-state) were assessed. Safety was monitored through Treatment-Emergent Adverse Events (TEAEs).

Results: Both formulations demonstrated comparable pharmacokinetic profiles meeting the criteria for bioequivalence within acceptable limits (80.00-125.00%). Ratio of Least-Squares (LS) mean difference was 95.64 (90% Confidence Interval (CI): 90.28-101.32) for AUC_0-τ, 91.47 (90% CI: 84.61-98.89) for C_maxSS and 91.27 (90% CI: 82.25-101.29) for percentage of fluctuation. Plasma concentration-time profiles were similar and no serious Adverse Events (AE) was reported. Commonly reported TEAEs for T included leukopenia, neutropenia AND dyspepsia while R commonly caused vomiting, injection site pain, urinary tract infection, hypertriglyceridemia, dizziness, orthostatic hypotension and headache.

Conclusion: Paliris LA^® and Invega Sustenna^® are bioequivalent in terms of pharmacokinetic profile and well-tolerated, supporting their interchangeability in treating SZ and SA disorders.