Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders

NCT00870727 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 0805-26MH 082119
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to develop a better tolerated and more effective pharmacologic treatment with individuals with Pervasive Developmental Disorder. This is a double-blind, placebo-controlled study of aripiprazole in the management of the maladaptive behaviors of Pervasive Developmental Disorder. The investigators hypothesize that aripiprazole will be more effective than placebo for reducing aggression, tantrum and self-injurious behavior in children with Pervasive Developmental Disorder.

Conditions

Pervasive Developmental Disorder

Keywords

PDD NOS

Outcome Measures

Primary Outcomes (2)

• Number of Participants Improved as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2)

  Clinical Global Impressions (Guy, 1976) global improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7, with lower scores indicating greater improvement (1=very much improved and 2=much improved). Participants with a CGI-I score of 1 or 2 were classified as improved. Four participants assigned to placebo completed an exit interview prior to week 8. One participant assigned to placebo and one participant assigned to aripiprazole withdrew from the study without completing an exit interview.

  Double-blind phase study exit - up to 8 weeks

• Mean Post-baseline Aberrant Behavior Checklist Irritability Subscale Score, Parent Report, Double-blind Phase

  The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Irritability subscale is 0 to 45. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints. Confidence intervals reflect a Bonferroni multiple testing correction accounting for the selection of two primary outcomes.

  Weeks 1, 2, 3, 4, 6 and 8

Secondary Outcomes (4)

• Mean Post-baseline Aberrant Behavior Checklist Hyperactivity Subscale Score, Parent Report, Double-blind Phase

  Weeks 1, 2, 3, 4, 6 and 8

• Mean Post-baseline Aberrant Behavior Checklist Inappropriate Speech Subscale Score, Parent Report, Double-blind Phase

  Weeks 1, 2, 3, 4, 6 and 8

• Mean Post-baseline Aberrant Behavior Checklist Social Withdrawal Subscale Score, Parent Report, Double-blind Phase

  Weeks 1, 2, 3, 4, 6 and 8

• Mean Post-baseline Aberrant Behavior Checklist Stereotypy Subscale Score, Parent Report, Double-blind Phase

  Weeks 1, 2, 3, 4, 6 and 8

Study Arms (2)

Arm 1. Aripiprazole oral product

EXPERIMENTAL

Participants will receive Aripiprazole oral product with a minimum dose of 2 mg per day to a maximum dose of 20 mg per day over 8-weeks of treatment.

Drug: Aripiprazole oral product

Arm 2. Placebo oral capsule

PLACEBO COMPARATOR

Participants will receive matching (identical in size and appearance to study drug) placebo oral capsules over 8-weeks of treatment.

Drug: Placebo oral capsule

Interventions

Aripiprazole oral product DRUG

Minimum dose of 2 mg per day to a maximum dose of 20 mg per day over 8-weeks of treatment.

Also known as: Abilify

Arm 1. Aripiprazole oral product

Placebo oral capsule DRUG

Placebo will be identical in size and appearance to study drug.

Also known as: Sugar pill

Arm 2. Placebo oral capsule

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male and female outpatients between the ages of 5 and 17 years and greater than or equal to 15 kg body weight.
• Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revised (DSM-IV-TR) diagnosis of Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS).
• Psychotropic medication-free for at least 2 days prior to screening laboratory tests and electrocardiogram (ECG).
• Significant irritability as determined by a Clinical Global Impression Severity score of greater or equal to 4 (Moderately ill) and a score of equal to or greater than 18 on the Aberrant Behavior Checklist Irritability Subscale.
• Intelligence quotient (IQ) of equal to or greater than 50 based on the Wechsler Intelligence Scale for Children (WISC), 4th edition; the Leiter International Test of Intelligence-Revised will be used if a child is nonverbal but thought to have an IQ greater than or equal to 50.

You may not qualify if:

• DSM-IV-TR diagnosis other than PDD NOS (autistic disorder, Asperger's disorder, Rett's disorder, or childhood disintegrative disorder), schizophrenia, bipolar disorder or substance abuse within the last 6 months.
• Comorbid disorder with possible association to autism (e.g., Fragile X Syndrome, Tuberous Sclerosis).
• A significant medical condition such as heart, liver, renal, or pulmonary disease, or a seizure disorder, as determined by history, physical examination, or laboratory testing.
• Subjects with an active seizure disorder (history of febrile seizures in early childhood will be considered.
• Females with a positive urine pregnancy test.
• Evidence of a prior adequate trial of aripiprazole (defined as equal to or greater than 2 weeks at equal to or greater than 5 mg per day. When there is not evidence of a prior adequate trial, subjects must be medication-free for a least 2 weeks prior to baseline.
• History of neuroleptic malignant syndrome.
• Subjects who, in the opinion of the investigator, are unsuitable in any other way to participate in this study, including being unable to comply with the requirements of the study for any reason.
• Hypersensitivity to aripiprazole \[e.g., allergic response or serious adverse effect\] (significant tachycardia).

Sponsors & Collaborators

• Indiana University: lead
• National Institute of Mental Health (NIMH): collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Riley Hospital for Children, Christian Sarkine Autism Treatment Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Child Development Disorders, Pervasive

Interventions

Aripiprazole; Sugars

Condition Hierarchy (Ancestors)

Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carbohydrates

Limitations and Caveats

The PI who conducted the trial left the institution, Indiana University, prior to data analysis. The institution negotiated/executed a data transfer agreement for the PI's primary mentor, Dr. Christopher McDougle, to analyze the data on her behalf.

Results Point of Contact

• Title: Christopher J. McDougle, MD
• Organization: Indiana University

cmcdougle@partners.org

781-860-1783

Study Officials

• Kimberly A. Stigler, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2009
• First Posted: March 27, 2009
• Study Start: February 1, 2009
• Primary Completion: March 1, 2015
• Study Completion: May 1, 2015
• Last Updated: January 2, 2019
• Results First Posted: November 28, 2018

Record last verified: 2018-03

Locations

US (1)