A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
Condition: Autistic Disorder; Autism
MeSH terms: Autistic Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to evaluate the effectiveness (change in level of irritability
      and related behaviors) and safety and tolerability of the administration of 2 different fixed
      dose levels of risperidone (an atypical antipsychotic drug) compared with placebo in children
      or adolescents who have autism, and to evaluate the safety and tolerability of the drug for
      additional 26 weeks after the initial 6-week study period.
    

Detailed description: 
      Autistic Disorder is a condition that develops early in childhood and persists throughout
      life. Seventy-five percent of children and adolescents with autistic disorder have
      irritability symptoms such as aggression towards others, deliberate self-injurious behavior,
      temper tantrums, and quickly changing moods. These symptoms affect their daily functioning
      such as school performance, interactions with family members and compliance to treatment.
      Risperidone is an atypical antipsychotic agent that has been recently approved for the
      treatment of irritability associated with Autistic Disorder in children and adolescents aged
      5 to 16 years. The approved dose range is 0.5-3 mg per day. The aim of this study is to
      evaluate the effectiveness (change in level of irritability and related behaviors) of a lower
      dose (0.125 mg or 0.175 mg risperidone per day depending on body weight). The study will
      include three treatment groups. A placebo group, a low dose risperidone group and a higher
      dose risperidone group (1.25 mg or 1.75mg per day depending on body weight). This phase of
      the study will be 6 weeks. During the study, neither investigators nor the patients will be
      told which treatment the patient received. This is called "double blind". The placebo
      treatment is not expected to be effective. The higher dose group is expected to be effective.
      At the end of the study, data from the lower dose group will be compared to the placebo group
      to see if it is effective. Another aim of this study is to evaluate the safety and
      tolerability of risperidone. At the end of the 6-week double-blind period, patients may enter
      a 6-month open-label period during which all patients will receive risperidone. During this
      phase of the study, the doses can be adjusted to a maximum of 1.25 mg or 1.75mg per day
      depending on body weight. Both investigator and the patient will know what dose the patient
      is taking. About 93 patients will be randomized. The study will be conducted by investigators
      from about 15 clinics. Assessments of effectiveness include the Aberrant Behavior Checklist
      (ABC) subscales including the irritability subscale (ABC-I), the Clinical Global Impression
      of Change (CGI C); the Clinical Global Impression of Severity (CGI-S); the response rate, and
      the Compulsions Subscale of the Children's Yale-Brown Obsessive Compulsive Scale (CY BOCS).
      Safety evaluations include monitoring of adverse events, physical examinations, clinical
      laboratory tests, nighttime sleep quality and daytime drowsiness, and extrapyramidal symptoms
      (EPS) as assessed using the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia
      Rating Scale (BARS) and the Simpson-Angus Scale (SAS). Venous blood samples will be collected
      for the determination of plasma concentrations of risperidone and 9-hydroxyrisperidone. The
      study hypotheses are that the higher dose level of risperidone is significantly superior to
      placebo as measured by change from baseline on the ABC-I Subscale score at end point (Week 6
      or early withdrawal) and that the lower dose level of risperidone is significantly superior
      to placebo as measured by change from baseline on the ABC-I Subscale score at end point (Week
      6 or early withdrawal). Double-blind phase: Risperidone oral solutions taken once daily.
      Depending on body weight patients take 1.25 mL or 1.75 mL of either a 0.1 mg/mL or a 1.0
      mg/mL risperidone solution or matching placebo, for 6 weeks. Open-label phase: Medication can
      be taken once or twice a day. Starting from 0.125mg or 0.175mg per day, drug levels are
      titrated over 2 weeks to a maximum dose level of 1.25 mg risperidone/day or 1.75 mg /day
      depending on body weight, for 26 weeks.
    

Intervention name(s): Placebo; Risperidone high dose; Risperidone low dose
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Oral solution qd or bid for 6 weeks; Risperidone oral solution 1.25 mg (if <45 kg) or 1.75 mg (if >=45 kg) qd or bid for 6 weeks; Risperidone oral solution 0.125 mg (if <45 kg) or 0.175 mg (if >=45 kg) qd or bid for 6 weeks
Intervention MeSH terms: Risperidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Irritability; Risperidone; Antipsychotic agent; Autism; Adolescents; Children