A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00576732
First received: December 17, 2007
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Autistic Disorder
Autism
Drug: Placebo
Drug: Risperidone high dose
Drug: Risperidone low dose
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Risperidone in the Treatment of Children and Adolescents With Autistic Disorder: A Double-Blind, Placebo-Controlled Study of Efficacy and Safety, Followed by an Open-Label Extension Study of Safety

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Change in Aberrant Behavior Checklist Irritability (ABC-I) Subscale [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    Measure of irritability symptoms of autism. Score range 0 to 45 (lower score = lesser severity).


Secondary Outcome Measures:
  • Number of Participants Who Had at Least 25% Improvement in ABC-I [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    ABC-I is a measure of irritability symptoms of autism with score range 0 to 45 (lower score = lesser severity).

  • Change in Clinical Global Impression Severity (CGI-S) [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    Investigator evaluation of severity of illness and functional impairment on a 7-point scale (1="not ill", 2="very mild", 3="mild", 4="moderate", 5="marked", 6="severe", 7="extremely severe").

  • Number of Participants Who Had Clinical Global Impression Change Ratings of Much or Very Much Improved. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Investigator impression of change over time from double-blind baseline on a 7-point scale (1="very much improved", 2="much improved", 3="minimally improved", 4="no change", 5="minimally worse", 6="much worse", 7="very much worse").

  • Change in Fasting Glucose (mg/dL) at 6 Weeks [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: Yes ]
  • Change in Insulin Resistance (IR) at 6 Weeks [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: Yes ]
    Insulin resistance calculated using the homeostatic model assessment 1 (HOMA1)formula: fasting glucose (mmol/L) times fasting insulin (uU/L) divided by 22.5. HOMA-IR is a widely used clinical tool for estimating insulin resistance based upon the balance between glucose output and insulin secretion. Normal values should be close to 1, while an increase indicates a decrease in insulin sensitivity (or increase in insulin resistance), a potential predictor for the development of Type 2 Diabetes Mellitus.

  • Change in Fasting Glucose (mg/dL) at 6 Months [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
  • Change in Insulin Resistance (IR) at 6 Months [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    Insulin resistance calculated using the homeostatic model assessment 1 (HOMA1) formula: fasting glucose (mmol/L) times fasting insulin (uU/L) divided by 22.5. HOMA-IR is a widely used clinical tool for estimating insulin resistance based upon the balance between glucose output and insulin secretion. Normal values should be close to 1, while an increase indicates a decrease in insulin sensitivity (or increase in insulin resistance), a potential predictor for the development of Type 2 Diabetes Mellitus.


Enrollment: 96
Study Start Date: December 2007
Study Completion Date: March 2010
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
Risperidone low dose Risperidone oral solution 0.125 mg (if <45 kg) or 0.175 mg (if >=45 kg) qd or bid for 6 weeks
Drug: Risperidone low dose
Risperidone oral solution 0.125 mg (if <45 kg) or 0.175 mg (if >=45 kg) qd or bid for 6 weeks
Experimental: 002
Risperidone high dose Risperidone oral solution 1.25 mg (if <45 kg) or 1.75 mg (if >=45 kg) qd or bid for 6 weeks
Drug: Risperidone high dose
Risperidone oral solution 1.25 mg (if <45 kg) or 1.75 mg (if >=45 kg) qd or bid for 6 weeks
Placebo Comparator: 003
Placebo Oral solution qd or bid for 6 weeks
Drug: Placebo
Oral solution qd or bid for 6 weeks

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.

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DSM-IV diagnosis of Autistic Disorder (299.00)
  • ABC-I Subscale score of greater than or equal to 18
  • CGI-S of greater than or equal to 4
  • mental age >18 months, body weight of at least 20 kg, seizure-free for at least 6 consecutive months and if on anticonvulsants must be on a dosage that has been stable for at least 4 weeks
  • Medication free for 1 week before the start of the study for all psychotropic drugs, except 4 weeks for fluoxetine and at least 8 weeks for injectable medications
  • Female patients must be premenarchal or sexually abstinent or, if heterosexually active, must practice an effective method of birth control.

Exclusion Criteria:

  • History of prior or current DSM-IV psychotic disorder (e.g., schizophrenia, bipolar disorder, other psychosis), Pervasive Developmental Disorder not otherwise specified (PDD NOS), Asperger's, or Rett's
  • Any history of hypersensitivity to risperidone, or its excipients in formulation, or other known drug allergy
  • Patients who received risperidone within 3 months before screening (except p.r.n. use)
  • Patients who did not demonstrate sufficient clinical response to an adequate trial of risperidone treatment in the past (an adequate trial is defined as a period of at least 4 weeks at an adequate dose)
  • Neurologic disorder (e.g., Neuroleptic Malignant Syndrome, seizure disorders that are unstable, seizure activity within the past 6 months)
  • History of alcohol or substance dependence within 3 months of screening
  • Female subject who is pregnant (positive beta-HCG) or breast feeding
  • Patients with existing moderate or severe EPS or history of tardive dyskinesia
  • Patients who have received an experimental drug or used an experimental medical device within 3 months before the planned start of treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00576732

Locations
United States, Alabama
Dothan, Alabama, United States
United States, Arizona
Phoenix, Arizona, United States
United States, California
Sacramento, California, United States
Santa Ana, California, United States
United States, Florida
Boca Raton, Florida, United States
Miami, Florida, United States
United States, Georgia
Smyrna, Georgia, United States
United States, Illinois
Hoffman Estates, Illinois, United States
Naperville, Illinois, United States
United States, Louisiana
Lake Charles, Louisiana, United States
United States, New York
Bronx, New York, United States
Manhasset, New York, United States
New York, New York, United States
Staten Island, New York, United States
United States, Ohio
Columbus, Ohio, United States
United States, Oklahoma
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
Houston, Texas, United States
United States, Virginia
Fairfax, Virginia, United States
Portsmouth, Virginia, United States
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00576732     History of Changes
Other Study ID Numbers: CR014740, RISAUT4002
Study First Received: December 17, 2007
Results First Received: September 2, 2010
Last Updated: April 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Irritability
Risperidone
Antipsychotic agent
Autism
Adolescents
Children

Additional relevant MeSH terms:
Autistic Disorder
Disease
Child Development Disorders, Pervasive
Mental Disorders Diagnosed in Childhood
Mental Disorders
Pathologic Processes
Risperidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on October 19, 2014