An Efficacy and Safety Study of Extended-Release (ER) Paliperidone in Adolescent Participants With Schizophrenia

A Randomized, Multicenter, Double-Blind, Active-Controlled, Flexible-Dose, Parallel-Group Study of the Efficacy and Safety of Extended Release Paliperidone for the Treatment of Symptoms of Schizophrenia in Adolescent Subjects, 12 to 17 Years of Age

The purpose of this study is to evaluate the efficacy and safety of extended-release (ER) paliperidone compared to aripiprazole (atypical antipsychotic) in symptomatic (having symptoms) adolescent participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations [imagining things], and withdrawal into the self) .

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Paliperidone extended release (ER); Drug: Aripiprazole

Detailed Description

This is a multi-center (conducted in more than 1 center), double-blind (neither physician nor participant knows the name of the assigned drug), randomized (study drug is assigned by chance), active-controlled (paliperidone ER is compared to aripiprazole), parallel-group (a medical research study comparing the response in 2 or more groups of participants receiving different treatments), flexible-dose (the physician has the freedom to give different doses to the participant depending on how they respond to treatment) study designed to determine the efficacy and safety of paliperidone ER in symptomatic adolescents (12 to 17 years of age) with schizophrenia. The total duration of the study will be approximately 29 weeks. The study consists of 3 phases: a Screening phase up to 3 weeks (with a possible overlapping washout period), a Double-blind acute phase of 8 weeks, and a Double-blind maintenance phase of 18 weeks. Participants will be randomly assigned to 1 of the 2 treatment groups (paliperidone ER or aripiprazole flexible oral doses). Dosage will be adjusted at the scheduled visits. Efficacy of the participants will primarily be evaluated through Positive and Negative Syndromes Scale (PANSS). Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 228
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Jaipur, India
  • Kanpur Uttarpradeh, India
  • Lucknow Gpo, India
  • Mangalore, India
  • Varanasi, India
• Romania
  • Bucharest, Romania
• Russian Federation
  • Chelyabinsk, Russian Federation
  • Ekaterinburg Na, Russian Federation
  • Krasnodar N/A, Russian Federation
  • Moscow N/A, Russian Federation
  • Moscow Russia, Russian Federation
  • Nizhniy Novgorod, Russian Federation
  • Novosibirsk, Russian Federation
  • Saint Petersburg, Russian Federation
  • Samara, Russian Federation
  • Saratov, Russian Federation
  • Smolensk Region N/A, Russian Federation
  • St Petersburg, Russian Federation
  • St-Petersburg, Russian Federation
  • Tomsk Na, Russian Federation
  • Yaroslavl N/A, Russian Federation
• Slovakia
  • Bratislava, Slovakia
• Spain
  • Badajoz, Spain
  • Esplugues De Llobregat, Spain
  • Madrid, Spain
  • Paterna, Spain
  • Sabadell, Spain
  • Sevilla, Spain
  • Valladolid, Spain
• Ukraine
  • Donetsk, Ukraine
  • Glevakha, Ukraine
  • Ivano-Frankivsk, Ukraine
  • Ivano-Frankovsk, Ukraine
  • Kharkiv, Ukraine
  • Kherson, Ukraine
  • Kiev, Ukraine
  • Poltava, Ukraine
  • Simferopol, Ukraine
• United States
  • Alabama
    • Dothan, Alabama, United States
  • California
    • Santa Ana, California, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Smyrna, Georgia, United States
  • Louisiana
    • Lake Charles, Louisiana, United States
    • Shreveport, Louisiana, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must currently meet the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for schizophrenia and have experienced symptoms of the illness for at least 1 year, and they should have had at least treatment with 1 antipsychotic before participation in this study
• Participants having a Positive and Negative Syndromes Scale (PANSS) score between 60 and 120 inclusive at Screening
• Female participants must be incapable of pregnancy, or if heterosexually active and capable of pregnancy, have been using an acceptable method of contraception for at least 1 month before study entry and agree to continue use contraception methods for the duration of the study, or if sexually abstinent (not having sexual intercourse) and capable of pregnancy, must agree to continue abstinence or to use an acceptable method of birth control
• Participants must not be a danger to themselves or others, and must have family support available to be maintained as out-patients
• Participants with a weight of equal to or greater than 29 kilogram

Exclusion Criteria:

• Participants with mild (not serious), moderate (medium level of seriousness), or severe (very serious, life threatening) mental retardation
• Participants with a known or suspected history of substance dependence (including alcohol, but excluding nicotine or caffeine) as per the DSM-IV criteria in the 3 months before Screening
• Participants with a history of certain neurological (pertaining to the nervous system) disorders or insulin-dependent diabetes mellitus (disorder in which there is decreased insulin in the body or the body's insulin is not effective, resulting in high blood sugar, increased thirst and urine, and many other side effects)
• Participants who have received a depot injectable antipsychotic within 2 treatment cycles before the Screening visit
• Participants who have received clozapine in 2 months before the Baseline visit (Day 1 of Week 1)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paliperidone extended-release (ER); Paliperidone ER will be administered as oral capsule at a dose of 6 milligram (mg) for 1 week and then will be administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Drug: Paliperidone extended release (ER); Paliperidone ER will be administered as oral capsule at a dose of 6 mg for 1 week and then will be administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.
Active Comparator: Aripiprazole; Aripiprazole will be administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4, 10 mg Days 5, 6 and 7; and then will be administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.	Drug: Aripiprazole; Aripiprazole will be administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4, 10 mg Days 5, 6 and 7; and then will be administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Day 56	The PANSS is a 30-item scale with each item rated on a scale of 1 (absent) to 7 (extreme psychopathology), designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening.	Baseline and Day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in PANSS Total Score at Day 182	The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening.	Baseline and Day 182
Change From Baseline in Marder Factor Negative Symptoms Score at Day 56 and 182	The PANSS negative subscale based on marder factor assesses 7 negative-symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology).	Baseline, Day 56 and Day 182
Change From Baseline in Other Marder Factors Scores at Day 56 and 182	The subscales based on marder factors are: positive symptoms, disorganised thoughts factor, uncontrolled hostility/excitement factor, and anxiety/depression factor. The symptoms are rated on a 7-point scale, with a range of 8 to 56 for positive symptoms, 7 to 49 for disorganized thoughts and 4 to 28 for Uncontrolled hostility/excitement and anxiety/depression. Higher score indicate worsening.	Baseline, Day 56 and 182
Change From Baseline in Other PANSS Factors and Subscales at Day 56 and 182	The PANSS provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each rated on a scale of 1 (absent) to 7 (extreme).	Baseline, Day 56 and 182
Number of Participants With Clinical Stability	Clinical stability is defined as a decrease of 20 percent or more from Baseline in PANSS total score and CGI-S score less than or equal to 4 at Days 56 and 182, no hospitalizations due to psychiatric illness and no emergence of clinically significant suicidal or homicidal ideation during the maintenance phase.	Day 56 and 182
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Days 56 and 182	The CGI-S rating scale is a 7-point global assessment that measures the Clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher scores indicate worsening.	Baseline, Day 56 and 182
Change From Baseline in Personal and Social Performance (PSP) Scores at Day 56 and 182	The PSP scale assesses degree of a participants' dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The results of the assessment are converted to a numerical score to rate degree of difficulty (1=absent to 6=very severe) in each of the 4 domains. Based on 4 domains there will be 1 total score (total score ranges from 1 to 100, divided into 10 equal intervals). Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision.	Baseline, Day 56 and Day 182
Number of Participants With PANSS Response	The PANSS is a 30-item scale with each item rated on a scale of 1 (absent) to 7 (extreme psychopathology), designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Participants with PANSS response were defined as those who achieved greater than or equal to 20 percent or higher reduction from Baseline in the PANSS total score at Day 56 and 182.	Day 56 and 182

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Savitz AJ, Lane R, Nuamah I, Gopal S, Hough D. Efficacy and safety of paliperidone extended release in adolescents with schizophrenia: a randomized, double-blind study. J Am Acad Child Adolesc Psychiatry. 2015 Feb;54(2):126-137.e1. doi: 10.1016/j.jaac.2014.11.009. Epub 2014 Nov 25.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: November 5, 2009
• First Submitted That Met QC Criteria: November 5, 2009
• First Posted (Estimate): November 6, 2009

Study Record Updates

• Last Update Posted (Estimate): June 21, 2013
• Last Update Submitted That Met QC Criteria: June 20, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Schizophrenia; Aripiprazole; Paliperidone
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole; Paliperidone Palmitate
• Other Study ID Numbers: CR016675; R076477PSZ3003 (Other Identifier: Janssen Research & Development, LLC)