A Study of the Efficacy (Effectiveness) of Paliperidone Palmitate in the Prevention of Recurrence of the Symptoms of Schizophrenia.

A Randomized Double-blind Placebo-controlled Parallel Group Study Evaluating Paliperidone Palmitate in the Prevention of Recurrence in Patients With Schizophrenia. Placebo Consists of 20% Intralipid (200 mg/mL) Injectable Emulsion.

The purpose of this study is to evaluate the efficacy of paliperidone palmitate compared with placebo in the prevention of recurrence of the symptoms of schizophrenia and to assess the safety and tolerability of paliperidone palmitate in patients with stable and symptomatic schizophrenia. The placebo used in this study was a nutritional substance known as 20% Intralipid emulsion given to patients requiring intravenous feedings.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Paliperidone Palmitate; Drug: Placebo

Detailed Description

Many patients with schizophrenia have difficulty adhering to a daily oral treatment regimen. Long-acting injectable formulations, such as long-acting injectable paliperidone palmitate, may provide therapeutic plasma concentrations over several weeks, thereby eliminating the need for daily oral medication and making compliance easier. This study is a randomized (patients will be assigned to different treatment groups based solely on chance), double-blind (neither the patient nor the physician will know if placebo or drug is being given and at what dose), placebo-controlled, parallel-group, multicenter study followed by an open-label extension period in patients with schizophrenia. The study is designed to evaluate the efficacy of paliperidone palmitate (a long-acting injectable formulation) in delaying the time to and decreasing the rate of recurrence compared with placebo in patients with schizophrenia. The study will consist of 5 periods: an up to 7-day screening/washout/tolerability period, a 9-week open-label transition period, a 24-week open-label maintenance period, a randomized, variable-length double-blind, placebo-controlled recurrence prevention period, and an up to 52-week open-label extension period. Patients will have intramuscular (i.m.) study drug injections and efficacy and safety evaluations performed every 4 weeks throughout the study. Efficacy will be evaluated during the study using a recurrence assessment, the Positive and Negative Symptom Scale for Schizophrenia (PANSS), the Clinical Global Impression - Severity (CGI-S) scale, and the Personal and Social Performance (PSP) scale. Safety will be assessed throughout the study by monitoring adverse events; use of extrapyramidal symptoms (EPS) rating scales (Abnormal Involuntary Movement Scale [AIMS], Barnes Akathisia Rating Scale [BARS], Simpson Angus Scale [SAS]); clinical laboratory testing; vital signs (temperature, blood pressure, and heart rate) measurements; electrocardiograms (ECGs); and physical examinations. Additionally, the patients will assess the tolerability of the injections by evaluating the pain of the injection and the pain at the injection sites. Tolerability test: 3 mg/day of oral ER OROS paliperidone for 4 days. Transition (9 wks): 50 mg eq. paliperidone palmitate i.m. dose on Day 1, then i.m. injections (25, 50, or 100 mg eq.) once every 4 wks (q4wk). Maintenance (24-wks): paliperidone palmitate i.m. injections (25, 50, or 100 mg eq.) q4wk. Recurrence Prevention: paliperidone palmitate i.m. injections (25, 50, or 100 mg eq. or placebo) q4wk. Open-label paliperidone palmitate (25, 50, 75, or 100 mg eq.) q4wk for 12 dosing periods.

• Study Type: Interventional
• Enrollment (Actual): 414
• Phase: Phase 3

Contacts and Locations

Study Locations

• Costa Rica
  • Costa Rica, Costa Rica
• Korea, Republic of
  • Gwangju, Korea, Republic of
  • Inchun, Korea, Republic of
  • Pusan, Korea, Republic of
  • Seoul, Korea, Republic of
• Mexico
  • Ciudad De Mexico, Mexico
  • Merida, Mexico
  • Monterrey, Mexico
• Romania
  • Bucharest, Romania
  • Bucuresti, Romania
  • Cluj-Napoca, Romania
  • Iasi, Romania
  • Sibiu, Romania
  • Tg Mures, Romania
  • Timisoara, Romania
• Russian Federation
  • Arkhangelsk, Russian Federation
  • Moscow, Russian Federation
  • Moscow N/A, Russian Federation
  • Moscow Russia, Russian Federation
  • Samara N/A, Russian Federation
  • St Petersburg N/A, Russian Federation
  • Yaroslavl, Russian Federation
• South Africa
  • Cape Town, South Africa
  • Centurion Gauteng, South Africa
  • Florida Johannesburg Gauteng, South Africa
  • Johannesburg, South Africa
• Taiwan
  • Changhua, Taiwan
  • Kaohsiung, Taiwan
  • Tainan, Taiwan
  • Taoyuan, Taiwan
• Ukraine
  • Dnepropetrovsk, Ukraine
  • Glevakha, Ukraine
  • Kharkiv, Ukraine
  • Kiev, Ukraine
  • Kyiv, Ukraine
  • Lvov, Ukraine
  • Odessa, Ukraine
  • Simferopol, Ukraine
  • Vinnitsa, Ukraine
• United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Cerritos, California, United States
    • Santa Ana, California, United States
  • Florida
    • Hialeah, Florida, United States
  • Illinois
    • Chicago, Illinois, United States
    • Granite City, Illinois, United States
  • Louisiana
    • Lake Charles, Louisiana, United States
    • Shreveport, Louisiana, United States
  • Mississippi
    • Flowood, Mississippi, United States
  • Missouri
    • St. Louis, Missouri, United States
  • New Jersey
    • Clementon, New Jersey, United States
  • New York
    • Cedarhurst, New York, United States
  • Ohio
    • Cleveland, Ohio, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Texas
    • Conroe, Texas, United States
    • Desoto, Texas, United States
    • Irving, Texas, United States
    • San Antonio, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who meet the diagnostic criteria for schizophrenia according to DSM-IV-TM for at least 1 year before screening
• have a PANSS score of <120
• have a body mass index (BMI) >/=15.0 kilogram (kg)/meter (m)2
• and have resided at the same address for at least 30 days

Exclusion Criteria:

• Patients unable to provide their own consent
• have been involuntarily committed to psychiatric hospitalization
• have primary, active DSM-IV-TM diagnosis other than schizophrenia
• who have a DSM-IV-TM diagnosis of active substance dependence within 3 months before screening (nicotine and caffeine are not exclusionary)
• have a history of treatment resistance as defined by failure to respond to 2 adequate trials (minimum of 4 weeks at a therapeutic dose) of different antipsychotic medications
• have a history of any severe preexisting gastrointestinal narrowing or inability to swallow the medication whole with water
• have a history of neuroleptic malignant syndrome (NMS)
• are at significant risk of suicidal or violent behavior
• current presence of any significant or unstable medication condition
• treatment with any protocol disallowed therapies
• clinically significant result from screening laboratory or ECG.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 001; Paliperidone Palmitate 25, 50, 75 or 100 mg eq every 4 wk for up to 24 mo	Drug: Paliperidone Palmitate; 25, 50, 75 or 100 mg eq every 4 wk for up to 24 mo
Placebo Comparator: 002; Placebo Placebo every 4 wk up to 24 mo	Drug: Placebo; Placebo every 4 wk up to 24 mo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary efficacy criteria for this study is the time from randomization to the first recurrence event during the double-blind recurrence prevention period	After 68 relapse events

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes from randomization to the end of the recurrence prevention period in PANSS (total and subscales), CGI-S, and PSP. Incidence of adverse events, labs and ECGs throughout study.	After 68 relapse events

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Collaborators: Janssen-Cilag International NV

Publications and helpful links

General Publications

• Ceraso A, Lin JJ, Schneider-Thoma J, Siafis S, Tardy M, Komossa K, Heres S, Kissling W, Davis JM, Leucht S. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2020 Aug 11;8(8):CD008016. doi: 10.1002/14651858.CD008016.pub3.
• Mathews M, Gopal S, Singh A, Nuamah I, Pungor K, Tan W, Soares B, Kim E, Savitz AJ. 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. Neuropsychiatr Dis Treat. 2020 Jun 19;16:1533-1542. doi: 10.2147/NDT.S221242. eCollection 2020.
• Weiden PJ, Kim E, Bermak J, Turkoz I, Gopal S, Berwaerts J. Does Half-Life Matter After Antipsychotic Discontinuation? A Relapse Comparison in Schizophrenia With 3 Different Formulations of Paliperidone. J Clin Psychiatry. 2017 Jul;78(7):e813-e820. doi: 10.4088/JCP.16m11308.
• Emsley R, Nuamah I, Gopal S, Hough D, Fleischhacker WW. Relapse After Antipsychotic Discontinuation in Schizophrenia as a Withdrawal Phenomenon vs Illness Recurrence: A Post Hoc Analysis of a Randomized Placebo-Controlled Study. J Clin Psychiatry. 2018 Jun 19;79(4):17m11874. doi: 10.4088/JCP.17m11874.
• Kozma CM, Slaton T, Dirani R, Fastenau J, Gopal S, Hough D. Changes in schizophrenia-related hospitalization and ER use among patients receiving paliperidone palmitate: results from a clinical trial with a 52-week open-label extension (OLE). Curr Med Res Opin. 2011 Aug;27(8):1603-11. doi: 10.1185/03007995.2011.595000. Epub 2011 Jun 22.
• Hough D, Gopal S, Vijapurkar U, Lim P, Morozova M, Eerdekens M. Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res. 2010 Feb;116(2-3):107-17. doi: 10.1016/j.schres.2009.10.026. Epub 2009 Dec 2.

Helpful Links

• A study of the efficacy of paliperidone palmitate in the prevention of recurrence of the symptoms of schizophrenia

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: May 17, 2005
• First Submitted That Met QC Criteria: May 17, 2005
• First Posted (Estimate): May 18, 2005

Study Record Updates

• Last Update Posted (Estimate): June 20, 2014
• Last Update Submitted That Met QC Criteria: June 19, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Schizophrenia; antipsychotic; Paliperidone palmitate; R092670; recurrence prevention
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease Attributes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Recurrence; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Paliperidone Palmitate
• Other Study ID Numbers: CR004198; R092670PSY3001