Model-Informed Clinical Development of 6-Monthly Injection of Paliperidone Palmitate in Patients with Schizophrenia: Dosing Strategies Guided by Population Pharmacokinetic Modeling and Simulation (Part II).

Background And Objective: Paliperidone palmitate 6-month (PP6M) intramuscular (IM) injection is the longest-acting treatment available for patients with schizophrenia. A population pharmacokinetic (popPK) modeling and simulation approach was deployed to inform dosing strategies for PP6M.

Methods: The extensive analysis database included 15,932 paliperidone samples from 700 patients receiving gluteal paliperidone palmitate 3-month (PP3M) or PP6M injections in the double-blind phase of a phase-3 noninferiority study (NCT03345342).

Model-Informed Clinical Development of Once-Every-6-Month Injection of Paliperidone Palmitate in Patients with Schizophrenia: A Pharmacometric Bridging Approach (Part I).

Background And Objective: A model-informed drug development (MIDD) approach was implemented for paliperidone palmitate (PP) 6-month (PP6M) clinical development, using pharmacokinetics and pharmacokinetic/pharmacodynamic model-based simulations.

Methods: PP6M pharmacokinetics were simulated by extending the PP 3-month (PP3M) pharmacokinetic model to account for increased injection volume, and hence dose. Contribution of the MIDD approach to the design of the pivotal PP6M phase-3 study (PP6M/PP3M noninferiority study, NCT03345342) investigating schizophrenia relapse rates was twofold: (1) PP6M dose selection, and (2) hypothesis generation that lower trough concentrations (C) associated with PP6M, relative to PP3M, were not associated with lower efficacy, which was to be evaluated in the phase-3 study.

Efficacy and safety of paliperidone palmitate 6-monthly long-acting injectable in reduction of relapses in patients with schizophrenia: An Asian subgroup analysis of phase 3, randomized study.

Background: Evaluate efficacy and safety of paliperidone palmitate 6-monthly (PP6M) for patients with schizophrenia in the Asian subgroup of a global, multicenter, noninferiority phase-3 study (NCT03345342).

Methods: Patients received paliperidone palmitate 1-monthly (PP1M, 100/150 mg eq.) or paliperidone palmitate 3-monthly (PP3M, 350/525 mg eq.

Efficacy and Safety of Paliperidone Palmitate 6-Month versus Paliperidone Palmitate 3-Month Long-Acting Injectable in European Patients with Schizophrenia: A Post Hoc Analysis of a Global Phase-3 Double-Blind Randomized Non-Inferiority Study.

Purpose: To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M).

Methods: This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq.

The Effect of Longer Dosing Intervals for Long-Acting Injectable Antipsychotics on Outcomes in Schizophrenia.

Medication nonadherence in schizophrenia can have serious implications including relapses and hospitalization. Long-acting injectable (LAI) antipsychotics require fewer administrations, while ensuring sustained medication coverage. In this review, we summarize the expected real-world benefits of longer dosing intervals in the management of schizophrenia.

Comparing Relapse Rates in Real-World Patients with Schizophrenia Who Were Adequately versus Not Adequately Treated with Paliperidone Palmitate Once-Monthly Injections Before Transitioning to Once-Every-3-Months Injections.

Purpose: This retrospective cohort study evaluated real-world data on relapses in adult patients with schizophrenia who transitioned to long-acting injectable paliperidone palmitate once-every-3-months (PP3M) following treatment with once-monthly paliperidone palmitate (PP1M).

Patients And Methods: Data derived from the IBM MarketScan Multi-State Medicaid Database were analyzed. Adults aged ≥18 years with ≥1 schizophrenia diagnosis claim and ≥12 months of continuous medical and prescription enrollment before and/or at index date of PP3M were eligible for inclusion.

A Randomized, Double-Blind, Multicenter, Noninferiority Study Comparing Paliperidone Palmitate 6-Month Versus the 3-Month Long-Acting Injectable in Patients With Schizophrenia.

Background: This double-blind (DB), randomized, parallel-group study was designed to evaluate efficacy and safety of paliperidone palmitate 6-month (PP6M) formulation relative to paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia.

Methods: Following screening, patients entered an open-label (OL) maintenance phase and received 1 injection cycle of paliperidone palmitate 1-month (PP1M; 100 or 150 mg eq.) or PP3M (350 or 525 mg eq.

Relapse and Treatment Adherence in Patients with Schizophrenia Switching from Paliperidone Palmitate Once-Monthly to Three-Monthly Formulation: A Retrospective Health Claims Database Analysis.

Purpose: Relapse and treatment adherence to paliperidone palmitate once-monthly (PP1M) and three-monthly (PP3M) formulations in patients with schizophrenia were evaluated and compared using health claims data.

Patients And Methods: Data (June 2015─June 2018) obtained from the MarketScan Multi-State Medicaid Database were retrospectively analyzed. Patients aged ≥18 years with ≥1 claim for schizophrenia diagnosis prior to and/or at index date (i.

Impact on carer burden when stable patients with schizophrenia transitioned from 1-monthly to 3-monthly paliperidone palmitate.

Rationale: Reducing the frequency of long-acting injectable antipsychotic medication may reduce carer burden.

Objectives: To evaluate the impact of reduced frequency of long-acting injectable antipsychotic medication on carer burden in stable patients with schizophrenia.

Methods: Carer burden was assessed using the Involvement Evaluation Questionnaire (IEQ) within a 52-week, prospective, single-arm, non-randomised, open-label, international, multicentre study evaluating the impact of transitioning stable patients with schizophrenia to paliperidone palmitate 3-monthly (PP3M) from paliperidone palmitate 1-monthly (PP1M).

Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview.

The availability of long-acting injectable (LAI) antipsychotics for the treatment of schizophrenia provides clinicians with options that deliver continuous drug exposure and may improve adherence compared with daily oral antipsychotics. However, all LAI antipsychotics have unique formulations and pharmacokinetic characteristics that have implications for medication selection, administration interval, and injection site. This review outlines key differences in drug formulations and pharmacokinetics among LAI antipsychotics.

Defining "Adequately Treated": A Post Hoc Analysis Examining Characteristics of Patients with Schizophrenia Successfully Transitioned from Once-Monthly Paliperidone Palmitate to Once-Every-3-Months Paliperidone Palmitate.

Purpose: Paliperidone palmitate once every 3 months (PP3M) is indicated in adults with schizophrenia adequately treated with once-monthly paliperidone palmitate (PP1M) for at least 4 months, in whom the last two consecutive doses are the same. The decision of when to transition to PP3M is based on the patient's symptom status while receiving PP1M.

Patients And Methods: In a double-blind relapse-prevention study (NCT01529515), patients who met Positive and Negative Syndrome Scale (PANSS) score stabilization criteria after 4 months of PP1M were eligible for transition to PP3M; those who continued to meet stabilization criteria after 12 weeks following an open-label PP3M dose were randomized to receive PP3M or placebo.

Effect of Paliperidone Palmitate 3-Month Formulation on Goal Attainment and Disability After 52 Weeks' Treatment in Patients with Clinically Stable Schizophrenia.

Purpose: This pragmatic clinical study aimed to assess goal attainment among patients with schizophrenia treated with paliperidone palmitate 3-monthly (PP3M) and its relation to their level of disability, and whether patients achieved symptomatic remission at the study endpoint.

Patients And Methods: Goal attainment was assessed as a secondary endpoint using Goal Attainment Scaling (GAS) within a 52-week, prospective, single-arm, non-randomized, open-label, international, multicenter study evaluating the impact of transitioning stable patients with schizophrenia from paliperidone palmitate 1-monthly (PP1M) to PP3M. Additional exploratory analyses were performed to investigate the relationship between disability and functioning as measured by the World Health Organization Disability Assessment Schedule (WHODAS), Version 2.

Stable patients with schizophrenia switched to paliperidone palmitate 3-monthly formulation in a naturalistic setting: impact of patient age and disease duration on outcomes.

Background: Paliperidone palmitate 3-monthly (PP3M) is a second-generation, long-acting injectable antipsychotic formulation indicated for the maintenance treatment of adults with schizophrenia first stabilized with paliperidone palmitate 1-monthly (PP1M). This exploratory subgroup analysis of the 52-week, phase 3b REMISSIO study analysed outcomes according to patient age and disease duration in a naturalistic clinical setting.

Methods: Outcomes of patients with schizophrenia were analysed according to age [<35 years ( = 123) ⩾35 years ( = 182)] and disease duration [⩽3 years ( = 72) >3 years ( = 233)].

Patients' Preference for Long-Acting Injectable versus Oral Antipsychotics in Schizophrenia: Results from the Patient-Reported Medication Preference Questionnaire.

Introduction: Understanding patients' preferences for long-acting injectable (LAI) or oral antipsychotics (pills) could help reduce potential barriers to LAI use in schizophrenia.

Methods: Post hoc analyses were conducted from a double-blind, randomized, non-inferiority study (NCT01515423) of 3-monthly vs 1-monthly paliperidone palmitate in patients with schizophrenia. Data from the Medication Preference Questionnaire, administered on day 1 (baseline; open-label stabilization phase), were analyzed.

Comparison of Relapse Prevention with 3 Different Paliperidone Formulations in Patients with Schizophrenia Continuing versus Discontinuing Active Antipsychotic Treatment: A Post-Hoc Analysis of 3 Similarly Designed Randomized Studies.

Background: Sudden discontinuation from antipsychotic treatment is a common occurrence in patients with schizophrenia. Lower rates of relapse could be expected for patients discontinuing treatment from longer-acting formulations vs their shorter-acting equivalents.

Objective: To compare relapse rates and time-to-relapse between the active (analogous to adherent patients) and placebo (analogous to non-adherent patients in the real-world) arms of three different formulations of paliperidone (oral paliperidone extended release [paliperidone ER], paliperidone palmitate once monthly [PP1M], and paliperidone palmitate three monthly [PP3M] long-acting injectables).

Improvement of Negative Symptoms in Schizophrenia with Paliperidone Palmitate 1-Month and 3-Month Long-Acting Injectables: Results from a Phase 3 Non-Inferiority Study.

Background: Negative symptoms in schizophrenia are associated with impairments in social and cognitive functioning leading to substantial long-term disability. Available antipsychotic treatments have demonstrated only modest benefit in the improvement of negative symptoms.

Objective: To compare improvements in negative symptoms among patients treated with paliperidone palmitate 3-month (PP3M) or paliperidone palmitate 1-month (PP1M) long-acting injectable (LAI) formulations.

Pharmacokinetic-Pharmacodynamic Characterization of Relapse Risk for Paliperidone Palmitate 1-Month and 3-Month Formulations.

Background: Pharmacokinetic-pharmacodynamic (PK/PD) models were developed to describe the relationship between the time course of paliperidone plasma concentrations and the risk of relapse of schizophrenia symptoms following administration of paliperidone palmitate 1-month (PP1M) and 3-month (PP3M) long-acting injectables, and to identify relevant covariates for relapse and dropout events.

Methods: Patient data from two global phase 3, relapse prevention studies comparing PP3M to placebo (study A) and PP3M to PP1M (study B) were analyzed. Dropout and relapse data were assessed using survival analysis as two separate single time-to-event models.

Clinical relevance of paliperidone palmitate 3-monthly in treating schizophrenia.

Antipsychotics are the mainstay in schizophrenia management, and long-acting injectable (LAI) antipsychotics contribute to the successful maintenance of treatment by improving non-adherence and preventing relapses. Paliperidone palmitate 3-monthly (PP3M) formulation is the only available LAI antipsychotic that offers an extended 3-month window of stable plasma drug concentration, enabling only four injections per year. This paper summarizes clinically relevant endpoints from available evidence for PP3M to bridge translational research gaps and provide measurable outcomes that can be interpreted in clinical practice.

Efficacy and safety of paliperidone palmitate 3-month formulation in Latin American patients with schizophrenia: A subgroup analysis of data from two large phase 3 randomized, double-blind studies.

Objective: To analyze the efficacy and safety of paliperidone palmitate 3-monthly (PP3M) in Latin American patients with schizophrenia vs. rest-of-world (ROW).

Methods: We analyzed data from two multinational, double-blind (DB), randomized, controlled phase 3 studies including patients with schizophrenia (DSM-IV-TR) previously stabilized on PP1M/PP3M (open-label [OL] phase).

Efficacy and safety of paliperidone palmitate 3-month versus 1-month formulation in patients with schizophrenia: comparison between European and non-European population.

Purpose: This randomized, double-blind (DB), non-inferiority phase 3 study was conducted to assess the efficacy and safety of paliperidone palmitate 3-month (PP3M) vs 1-month formulation (PP1M) in European and non-European patients with schizophrenia.

Patients And Methods: In this randomized, DB, parallel-group study, adult patients (18-70 years) with schizophrenia (per DSM-IV-TR) having Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120; previously stabilized on PP1M were enrolled. The study had 4 phases: screening (3 weeks), open-label (OL) stabilization (17 weeks), DB (48 weeks) and follow-up (4-12 weeks) phase.