A Comparative Pharmacokinetic Evaluation of Paliperidone Palmitate Extended-Release Injectable Suspensions: An Open Label, Randomized, Twotreatment, Two-Period, Two-Sequence, Multiple Dose, Steady State Crossover Bioequivalence Study in Patients with

<p>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 plasma concentration at steady state (CmaxSS), area under concentration-time curve (AUC0-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) geometric mean was 95.64 [90% Confidence Interval (CI): 90.28-101.32] for AUC0-τ, 91.47 (90% CI: 84.61-98.89) for CmaxSS and 91.27 (90% CI: 82.25-101.29) for %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. Conclusions: Paliris LA® and Invega Sustenna® are bioequivalent in terms of pharmacokinetic profile and well-tolerated, supporting their interchangeability in treating SZ and/or SA disorders.</p>