A Study to Evaluate the Efficacy and Safety of Risperidone (R064766) in Children and Adolescents With Irritability Associated With Autistic Disorder

A Double-blind, Placebo-controlled Study, Followed by an Open-label Extension Study Evaluating the Efficacy and Safety of Risperidone (R064766) in Children and Adolescents With Irritability Associated With Autistic Disorder

The purpose of this study is to evaluate the efficacy of risperidone compared with placebo in children and adolescents with irritability associated with autistic disorder.

Study Overview

• Status: Completed
• Conditions: Autistic Disorder in Children and Adolescents
• Intervention / Treatment: Drug: Risperidone; Drug: Placebo

Detailed Description

This is a randomized (the drug is assigned by chance), 8-week, double-blind (neither physician nor patient knows the treatment that the patient receives), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (each group of patients will be treated at the same time), flexible-dose, multicenter study. It will be followed by a 48-week, flexible-dose, open-label (all people know the identity of the intervention) extension, to evaluate the efficacy and safety of risperidone in children and adolescents with a diagnosis of autistic disorder (severe form of pervasive developmental disorder) who have associated irritability. The study consists of up to 2-week screening phase, an 8-week double-blind phase, a 48-week open-label phase, and a 1-week follow-up phase.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fuchu, Japan
  • Fukui, Japan
  • Hirakata, Japan
  • Ichikawa, Japan
  • Kanzaki, Japan
  • Kobe, Japan
  • Kodaira, Japan
  • Kurashiki, Japan
  • Neyagawa, Japan
  • Okayama, Japan
  • Sakai, Japan
  • Shimotsuke, Japan
  • Tokyo, Japan
  • Toyama, Japan
  • Tsu, Japan
  • Tsuyama, Japan
  • Yokohama, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnostic for autistic disorder
• A Clinical Global Impression - Severity (CGI-S) score of =>4 and an Aberrant Behavior Checklist - Japanese Version (ABC-J) Irritability Subscale score of =>18
• Patients with mental age of >18 months as measured by appropriate developmental or mental scales
• Patients who have an appropriate caregiver, eg, parent or study-site personnel, who is able to observe the patient's condition, provide information, and evaluate the patient's response appropriately

Exclusion Criteria:

• Patients with previous or current psychotic disorder (eg, schizophrenia, bipolar disorder, or other psychiatric disorders) or with pervasive developmental disorder not otherwise specified, Asperger's disorder, Rett's disorder, pediatric destructive behavior disorder, or substance dependence
• Patients with a clinically significant endocrine, metabolic, cardiac, hepatic, renal, or pulmonary disorder, or hypertension
• Weight of <15 kg at the time of screening and baseline
• Patients with QTc>450 msec in the standard 12-lead electrocardiogram (ECG) at the time of screening
• Patients with known hypersensitivity to risperidone or paliperidone

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: Risperidone; Subjects weighing less than 20 kilogram (kg) received risperidone 0.25 milligram per day (mg/day) up to Day 4. On Day 4, dose was titrated in increments of 0.25 mg/day (up to a daily dose of 1.0 mg) at the regular study visit thereafter till Week 8. Subjects weighing greater than or equal to (>=) 20 kg received risperidone 0.5 mg/day up to Day 4. On Day 4, dose was titrated in increments of 0.5 mg per day (up to a daily dose of 2.5 mg) at the regular visit thereafter till Week 8. The maximum daily dose for subjects weighing >= 45 kg was 3.0 mg. For subjects weighing >=45 kg, the maximum daily dose was 3.0 mg.	Drug: Risperidone; Subjects weighing less than 20 kilogram (kg) received risperidone 0.25 milligram per day (mg/day) up to Day 4. On Day 4, dose was titrated in increments of 0.25 mg/day (up to a daily dose of 1.0 mg) at the regular study visit thereafter till Week 8. Subjects weighing greater than or equal to (>=) 20 kg received risperidone 0.5 mg/day up to Day 4. On Day 4, dose was titrated in increments of 0.5 mg per day (up to a daily dose of 2.5 mg) at the regular visit thereafter till Week 8. The maximum daily dose for subjects weighing >= 45 kg was 3.0 mg. For subjects weighing >=45 kg, the maximum daily dose was 3.0 mg.
Placebo Comparator: Placebo; Subjects will receive placebo matching with risperidone orally up to 8 weeks.	Drug: Placebo; Subjects will receive placebo matching with risperidone orally up to 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change from baseline in the Aberrant Behavior Checklist-Japanese Version (ABC-J) Irritability Subscale scores	The ABC-J Irritability subscale consists of 15 items. Each item scores range from 0 to 3: 0 = No problem, 1 = Mild aberrant behavior, 2 = Moderate aberrant behavior, and 3 = Severe aberrant behavior. Higher scores represent worse condition.	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes from baseline in the subscale scores of Aberrant Behavior Checklist-Japanese Version (ABC-J) at each evaluation of the double-blind phase	The ABC-J consists of 58 items divided into 5 subscales: Irritability, Lethargy and Social withdrawal, Stereotypic behavior, Hyperactivity/Noncompliance, and Inappropriate speech. Each item scores range from 0 to 3: 0 = No problem, 1 = Mild aberrant behavior, 2 = Moderate aberrant behavior, and 3 = Severe aberrant behavior. Higher scores represent worse condition.	Baseline, Week 2, Week 4, Week 6
The changes from baseline in the subscale scores of Aberrant Behavior Checklist-Japanese Version (ABC-J) at each evaluation of the open-label phase	The ABC-J consists of 58 items divided into 5 subscales: Irritability, Lethargy and Social withdrawal, Stereotypic behavior, Hyperactivity/Noncompliance, and Inappropriate speech. Each item scores range from 0 to 3: 0 = No problem, 1 = Mild aberrant behavior, 2 = Moderate aberrant behavior, and 3 = Severe aberrant behavior. Higher scores represent worse condition.	Baseline, Week 2, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48
The changes from baseline in scores of the Clinical Global Impression - Severity (CGI-S) at each evaluation time point of the double-blind phase	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 patient. 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 patients". Higher scores indicate worsening.	Baseline, Week 1, Week 2, Week 3, Week 4, Week 6, Week 8
The changes from baseline in scores of the Clinical Global Impression - Severity (CGI-S) at each evaluation time point of the open-label-phase	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 patient. 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 patients". Higher scores indicate worsening.	Baseline, Week 1, Week 2, Week 3, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48
The changes from baseline in scores of the Children's Global Assessment Scale (C-GAS) at each evaluation time point of the double-blind phase and open-label-phase	The C-GAS rates the patient's general psychological and social functioning on scores ranging from 1 through 100. Lower scores (range 1-10) mean that the patient needs constant supervision; higher scores (range 91-100) mean that the patient has a superior functioning in all areas.	Baseline, Week 4, Week 8
The changes from baseline in scores of the Children's Global Assessment Scale (C-GAS) at each evaluation time point of open-label-phase	The C-GAS rates the patient's general psychological and social functioning on scores ranging from 1 through 100. Lower scores (range 1-10) mean that the patient needs constant supervision; higher scores (range 91-100) mean that the patient has a superior functioning in all areas.	Baseline, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48
The Clinical Global Impression-Change (CGI-C) at each evaluation time point of the double-blind phase	The CGI-C assesses the patient's condition on the basis of the rater's impression, on a 7-point scale ranging from 1 (Very much improved) to 7 (Very much worse).	Week 1, Week 2, Week 3, Week 4, Week 6, Week 8
The Clinical Global Impression-Change (CGI-C) at each evaluation time point of the open label-phase	The CGI-C assesses the patient's condition on the basis of the rater's impression, on a 7-point scale ranging from 1 (Very much improved) to 7 (Very much worse).	Week 1, Week 2, Week 3, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48
The Parent Satisfaction Questionnaire (PSQ) at each evaluation time point of the double-blind phase	The PSQ evaluates the caregiver's satisfaction with the study drug.	Week 1, Week 2, Week 3, Week 4, Week 6, Week 8
The Parent Satisfaction Questionnaire (PSQ) at each evaluation time point of the open label-phase	The PSQ evaluates the caregiver's satisfaction with the study drug.	Week 1, Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Publications and helpful links

Helpful Links

• A Double-blind, Placebo-controlled Study, Followed by an Open-label Extension Study Evaluating the Efficacy and Safety of Risperidone (R064766) in Children and Adolescents with Irritability Associated with Autistic Disorder

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: June 19, 2012
• First Submitted That Met QC Criteria: June 19, 2012
• First Posted (Estimate): June 21, 2012

Study Record Updates

• Last Update Posted (Estimate): October 15, 2015
• Last Update Submitted That Met QC Criteria: October 13, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Adolescents; Children; Irritability; Autistic disorder; Autistic disorder in children and adolescents; Risperidone (R064766)
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Disease; Autistic Disorder; 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 Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: CR100877; RIS-AUT-JPN-01 (Other Identifier: Janssen Pharmaceutical K.K., Japan)