This multicenter, randomized, open-label, parallel-group, multiple-dose study is designed to evaluate the bioequivalence, at pharmacokinetic steady state, of a paliperidone palmitate injection manufactured by CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd. (Test Group) and a paliperidone palmitate injection manufactured by Janssen Pharmaceutica N.V. (Reference Group) in patients with schizophrenia in China. Bioequivalence will be assessed based on steady-state pharmacokinetic parameters after repeated intramuscular administration (e.g., Cmax,ss and AUCτ). The safety and tolerability of the test and reference products will also be evaluated.
Purpose: This trial was conducted to evaluate the bioequivalence of a test (T) and a reference (R) formulation of once-monthly paliperidone palmitate (PP1M) in patients with schizophrenia. Patients and methods: In this randomized, open-label, parallel-group, steady-state bioequivalence study, patients with stabilized schizophrenia were randomized 1:1 to receive T or R formulation. The regimen was 150 mg deltoid on Day 1, then 100 mg deltoid on Day 8, followed by five subsequent 100 mg gluteal injections every 28 days. The primary objective was to demonstrate steady-state bioequivalence. The primary endpoints were key pharmacokinetic parameters of paliperidone, including steady-state maximum concentration (Cmax,ss) and the area under the concentration-time curve over a dosing interval at steady state (AUCτ,ss). Bioequivalence was shown if the 90% confidence interval (CI) for the ratio of the geometric least squares means of the pharmacokinetic parameters (AUCτ,ss and Cmax,ss) fell within 80%-125%.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
256
Paliperidone palmitate injection will be administered intramuscularly according to two dosing regimens based on participants' prior exposure to paliperidone palmitate: 1. Participants with no prior use of paliperidone palmitate injection, or whose last dose was administered more than 6 months ago (for the once-monthly formulation), or more than 5 half-lives ago (for the once-every-3-months formulation): Day 1: 150 mg, deltoid muscle Day 8: 100 mg, deltoid muscle Followed by 100 mg every 28 days thereafter Approximate treatment duration: 148 days 2. Participants who have previously received at least 3 injections (including 150 mg Day 1 loading dose and 100 mg Day 8 loading dose, deltoid muscle) of the once-monthly formulation (100 mg) of paliperidone palmitate and whose last dose was given within 4 to 6 weeks prior to enrollment: Continue with 100 mg every 28 days Approximate treatment duration: 113 days
Paliperidone palmitate injection will be administered intramuscularly according to two dosing regimens based on participants' prior exposure to paliperidone palmitate: 1. Participants with no prior use of paliperidone palmitate injection, or whose last dose was administered more than 6 months ago (for the once-monthly formulation), or more than 5 half-lives ago (for the once-every-3-months formulation): Day 1: 150 mg, deltoid muscle Day 8: 100 mg, deltoid muscle Followed by 100 mg every 28 days thereafter Approximate treatment duration: 148 days 2. Participants who have previously received at least 3 injections (including 150 mg Day 1 loading dose and 100 mg Day 8 loading dose, deltoid muscle) of the once-monthly formulation (100 mg) of paliperidone palmitate and whose last dose was given within 4 to 6 weeks prior to enrollment: Continue with 100 mg every 28 days Approximate treatment duration: 113 days
Beijing Anding Hospital Capital Medical University
Beijing, Beijing Municipality, China
Title:Steady-State Peak Concentration (Cmax,ss) of Paliperidone After Intramuscular Administration.
Steady-state maximum plasma concentration (Cmax,ss) will be determined to assess bioequivalence between the test and reference formulations of paliperidone palmitate injection after multiple intramuscular doses in patients with schizophrenia.
Time frame: Day148~Day176
Area Under the Concentration-Time Curve over Dosing Interval (AUCτ,ss) of Paliperidone After Intramuscular Administration.
Area under the plasma concentration-time curve during the dosing interval (AUCτ,ss) will be determined to assess bioequivalence between the test and reference formulations of paliperidone palmitate injection after multiple intramuscular doses in patients with schizophrenia.
Time frame: Day148~Day176
Steady-State Trough Concentration (Ctau,ss)
Steady-state plasma trough concentration (Ctau,ss) of paliperidone will be measured to further characterize pharmacokinetics and assess bioequivalence between test and reference group.
Time frame: Day1~Day176
Steady-State Average Concentration (Cav,ss)
Average plasma concentration during the dosing interval (Cav,ss) will be evaluated at steady state.
Time frame: Day1~Day176
Steady-State Minimum Concentration (Cmin,ss)
Minimum plasma concentration during the dosing interval (Cmin,ss) at steady state will be determined.
Time frame: Day1~Day176
Time to Maximum Concentration at Steady State (Tmax,ss)
The time to reach maximum plasma concentration (Tmax,ss) will be assessed at steady state.
Time frame: Day1~Day176
Degree of Fluctuation (DF) and Swing at Steady State
The degree of fluctuation (DF) and swing of paliperidone plasma concentrations will be calculated at steady state.
Time frame: Day1~Day176
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Number and percentage of participants experiencing ≥1 treatment-emergent adverse event (TEAE) after first dose; events coded by MedDRA (System Organ Class and Preferred Term); severity (mild/moderate/severe) and relationship to study drug assessed by investigator.
Time frame: Day1~Day176
Number of Participants With Serious Adverse Events (SAEs)
Number and percentage of participants experiencing ≥1 SAE, defined per ICH-GCP criteria; events coded by MedDRA (SOC/PT).
Time frame: Day1~Day176
Clinical Global Impression-Severity (CGI-S)
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score Mean (SD) change in CGI-S score from baseline to end of treatment. Clinical Global Impression - Severity (CGI-S): The Clinical Global Impression - Severity Scale ranges from 1 to 7 (1 = normal, not at all ill; 7 = among the most extremely ill), and higher scores indicate worse clinical severity (worse outcome).
Time frame: Day1~Day176
Proportion of Participants With Suicidal Ideation or Behavior (C-SSRS)
Number and percentage of participants with suicidal ideation (items 4 or 5) and/or any suicidal behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS). Columbia-Suicide Severity Rating Scale (C-SSRS): The Columbia-Suicide Severity Rating Scale rates suicidal ideation severity from 1 to 5 (0 = no suicidal ideation; 5 = most severe ideation), while suicidal behavior is recorded as present/absent; higher ideation category indicates a worse outcome (greater suicide risk).
Time frame: Day1~Day176
Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Score
Mean (SD) change in BARS global score from baseline to end of treatment. Barnes Akathisia Rating Scale (BARS): The Barnes Akathisia Rating Scale global score ranges from 0 to 5 (0 = no akathisia; 5 = severe akathisia), and higher scores indicate more severe akathisia (worse outcome).
Time frame: Day1~Day176
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score
Mean (SD) change in AIMS total score from baseline to end of treatment. Abnormal Involuntary Movement Scale (AIMS): The Abnormal Involuntary Movement Scale total score commonly uses the sum of items 1-7 and ranges from 0 to 28 (0 = no abnormal movements; 28 = maximum severity on rated items); higher scores indicate more severe abnormal involuntary movements (worse outcome).
Time frame: Day1~Day176
Change From Baseline in Simpson-Angus Scale (SAS) Total Score
Mean (SD) change in SAS total score from baseline to end of treatment. Simpson-Angus Scale (SAS): The Simpson-Angus Scale total score ranges from 0 to 40 (10 items each scored 0-4), and higher scores indicate more severe drug-induced parkinsonism (worse outcome).
Time frame: Day1~Day176
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