A Study of the Effectiveness and Safety of Risperidone Versus Placebo in the Treatment of Children With Autistic Disorder and Other Pervasive Developmental Disorders (PDD)

Condition(s) targeted: Asperger Syndrome; Developmental Disabilities; DCild Development Disorders, Pervasive; Autistic Disorder; Rett Syndrome

Intervention: risperidone (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Janssen-Ortho Inc., Canada

Official(s) and/or principal investigator(s):
Janssen-Ortho Inc. Clinical Trial, Study Director, Affiliation: Janssen-Ortho Inc., Canada

The purpose of the study is to evaluate the effectiveness of an oral solution of risperidone (an antipsychotic medication) versus placebo in the treatment of behavioral symptoms in children with Pervasive Developmental Disorders (PDD).

Official title: Efficacy And Safety Of Risperidone In The Treatment Of Children With Autistic Disorder And Other Pervasive Developmental Disorders: A Canadian, Multicenter, Double-Blind, Placebo-Controlled Study

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Change in the Irritability Subscale of the Aberrant Behavior Checklist (ABC) and other ABC subscales at end of treatment compared with baseline

Secondary outcome: Change from baseline to end of treatment in Nisonger Child Behavior Rating Form (N-CBRF), Visual Analogue Scale (VAS), and Clinical Global Impression (CGI); incidence of adverse events throughout study.

Detailed description: The Pervasive Developmental Disorders (PDD) are a group of neuropsychiatric disorders, including autistic disorder, characterized by specific delays and deviance in social, communicative, and cognitive development with an onset typically in the first years in life. Children with PDD may show multiple, serious symptoms including hyperactivity, inattention, impulsive and aggressive behavior, repetitive movements or speech patterns, sleep disorders, screaming, and self-injurious behavior. Drug studies to date have suggested that different behavioral symptoms of PDDs respond to neuroleptics, such as risperidone. This is a randomized, double-blind, placebo-controlled study to evaluate the effectiveness of risperidone (0. 02 to 0. 06 mg/kg/day) compared with placebo in the treatment of behavioral symptoms in children 5 to 12 years of age with Pervasive Developmental Disorders (PDD). Patients receive study medication (risperidone or placebo) to be taken orally once a day at gradually increasing doses up to a maximum of 0. 06 mg/kg, adjusted at weekly intervals to achieve optimal effectiveness while minimizing any intolerance to the drug. Treatment continues at the optimal dose through Week 8. A parent or caregiver evaluates the child's behavior and symptoms at scheduled office visits during the course of treatment. The primary measure of effectiveness is the change in the Irritability Subscale of the Aberrant Behavior Checklist (ABC) and other ABC subscales at end of treatment compared with baseline. Additional assessments of effectiveness include: the Nisonger Child Behavior Rating Form (N-CBRF); the Visual Analogue Scale (VAS), a measure of the patient's most disturbing symptom; and the Clinical Global Impression (CGI) of the overall severity of the disorder. Safety assessments include the incidence of adverse events throughout the study; measurement of vital signs (pulse, temperature, blood pressure), body weight, and evaluation of the presence and severity of extrapyramidal symptoms by the Extrapyramidal Symptom Rating Scale (ESRS) at specified intervals; clinical laboratory tests (hematology, biochemistry, urinalysis) before study initiation and at the end of treatment. The study hypothesis is that risperidone is more effective than placebo for the treatment of behavioral symptoms in children aged 5 to 12 years with Pervasive Developmental Disorders (PDD).

Risperidone oral solution 1 mg/mL or placebo, taken orally, once daily. Days 1 - 2, dose is

0. 01 mg/kg body weight. Days 3 - 7 dose is 0. 02 mg/kg, increasing on Days 8 - 14 to 0. 04

mg/kg (maximum), and 0. 06 mg/kg (maximum) through 8 weeks. Dosage may be adjusted at investigator's discretion.

Minimum age: 5 Years. Maximum age: 12 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of Pervasive Developmental Disorders (Autistic Disorder, Rett's Disorder,

Childhood Disintegrative Disorder, Asperger's Disorder, or Pervasive Development Disorder not Otherwise Specified) by Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), Axis I criteria

- With a total score of >=30 on the Childhood Autism Rating Scale (CARS)

- Receiving treatment as an out-patient

- Healthy on the basis of a physical examination, electrocardiogram (ECG), and medical

history at start of the study

Exclusion Criteria:

- Diagnosis of schizophrenia or other psychotic disorders by DSM-IV criteria

- Seizure during 3 months prior to study initiation or currently being treated with more

than one anticonvulsant drug

- History of tardive dyskinesia (a complication of neuroleptic therapy involving

involuntary movements of facial muscles)

- Neuroleptic malignant syndrome (a rare psychotropic-drug reaction, which may be

characterized by confusion, reduced consciousness, high fever or pronounced muscle stiffness)

- Known hypersensitivity, intolerance, or unresponsiveness to risperidone

Starting date: April 1999
Ending date: December 2001
Last updated: May 11, 2007