Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders

Pervasive developmental disorders (PDDs) are characterized by severe impairments in social
interaction and communication in addition to restricted patterns of interests and activities.
Research suggests that a dysregulation of the dopamine and serotonin systems contributes to
these interfering behaviors in individuals with PDD. After benefits of typical neuroleptics
were reported in subjects with PDD, research shifted to the atypical antipsychotics which
have been shown to be better tolerated and effective in this population. However, the
atypical antipsychotics have also been associated with adverse effects. Thus there remains a
need for a novel pharmacotherapy that would be safe and effective for children and
adolescents with PDDs. The primary objectives of this study are to determine whether
aripiprazole is effective and well tolerated for irritability in children and adolescents
with PDD not otherwise specified (NOS) during an 8-week acute phase and whether the
effectiveness and tolerability of aripiprazole is maintained during a 16-week continuation
phase.

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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).