Buspirone in the Treatment of 2-6 Year Old Children With Autistic Disorder

This is a multi-center, randomized, placebo-controlled, double-masked study of 166 evaluable
participants taking buspirone twice daily for 6 months. Children aged 2-6 years with autism
will be randomized to receive one of three treatments: 2.5mg, 5.0mg, or matched placebo. The
placebo controlled trial will be followed by an optional follow-up trial to assess the long
term safety of buspirone. In addition, a PET scan of serotonin synthesis and plasma
serotonin will be measured at baseline to determine whether these measures are predictors of
drug response. This trial is aimed at the core features of autism. The outcome measures for
efficacy will be examiner and parent ratings on psychological tests and questionnaires. The
outcome measure for the primary objective will be the Autism Diagnostic Observation Scale
(ADOS) Composite Total score. The behavioral outcomes for the secondary aims are delineated
in the study design.

Inclusion Criteria:

- Participants: must meet the study definition for diagnosis of autistic disorder as
determined by clinical diagnosis based upon DSM-IV criteria, the Autism Diagnostic
Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS)
performed at baseline 1. ADI-R will be conducted by trained study staff at Baseline 1
Visit. If the participant has had an ADI-R in the past 12 months, this will be
accepted provided the person administering and scoring the test is site personnel
validated for the study.

- Age 2 to less than 6 years, male and female.

- Parent/Legal Guardian/Caregiver must be able to understand , read and speak English

- Written Informed Consent.

Exclusion Criteria:

- Presence or history of neurological disorders, including seizure disorders (abnormal
EEG without seizures will not be excluded), PKU, tuberous sclerosis, Rett syndrome,
Fragile X syndrome, Down Syndrome and traumatic brain injury.

- Other medical or behavioral problems requiring medications which are centrally
active.

- Clinical or laboratory evidence of renal or hepatic disease (SGPT, GGT > 2 x normal
value, and serum creatinine > 1.5 x normal value).

Treatment with any medication known to alter the activity of the CYP3A4 enzyme including
ketoconazole, itraconazole, grapefruit juice, erythromycin, clarithromycin, cimetidine,
verapamil, diltiazem, rifampin, phenytoin, phenobarbital, or carbamazepine within the
previous 2 months and for the duration of the study is prohibited.

- Use of centrally acting drugs during the 6 weeks prior or during the study. These
drugs include but are not limited to neuroleptics, benzodiazepines, anticonvulsants
and antidepressants. Shorter times may be considered depending on the half life of
the drug.

- Prior treatment for periods longer than two weeks with buspirone or selective
serotonin reuptake inhibitors. This includes herbal substances such as St John's Wort
which have similar pharmacological actions.

- Known allergies to study medication.

- Unable to provide the required blood samples.