A Prospective Open-label Study of Aripiprazole in Fragile X Syndrome

This 12-week prospective, open-label study design was chosen to gather pilot data for potential future lager scale, double-blind, placebo-controlled studies in Fragile X Syndrome.

We hypothesize that aripiprazole will be effective in decreasing aggression, SIB, agitation, and interfering repetitive behavior commonly observed in individuals with Fragile X Syndrome. We also hypothesize that aripiprazole will be well tolerated.

Inclusion criteria

• Males and females between the ages of 5 and 35 years and
• Body weight greater than or equal to 15 kg
• Confirmed diagnosis of Fragile X Syndrome based upon genetic testing results.
• Outpatients.
• Psychotropic medication-free for at least 2 weeks prior to screening laboratory tests and electrocardiogram. (Except 5 weeks for fluoxetine and 4 weeks for all typical and atypical antipsychotics that have been administered for at least a 4 week period.) Exceptions to medication-free status will include drugs given at bedtime targeting insomnia. Such drugs may include melatonin, clonidine, chloral hydrate, diphenhydramine, ramelteon, benzodiazepines, or other sedative-hypnotics.
• Clinical Global Impression Scale Severity score (CGI-S) of at greater than or equal to 4 (Moderately Ill)
• A score of at greater than or equal to 18 on the Irritability subscale of the Aberrant Behavior Checklist (ABC) at screen and baseline.
• Mental age of greater than or equal to 18 months as measured by the Wechsler, revised Leiter, or Mullen tests
• Each subject must be in good physical health as determined by screening procedures which will include a detailed medical history, complete physical and neurological examination.

Exclusion criteria

• DSM-IV diagnosis of schizophrenia, another psychotic disorder, bipolar disorder or alcohol or other substance abuse within the last 6 months.
• A significant medical condition such as heart, liver, renal or pulmonary disease, or an actively treated seizure disorder, as determined by history, physical examination or laboratory testing.
• Subjects with an unstable seizure disorder will be excluded.
• Females with a positive urine pregnancy test.
• Evidence of a prior adequate trial of aripiprazole (defined as a duration of greater than or equal to 2 weeks at a dose of at least 5 mg per day). When there is not evidence of a prior adequate trial of aripiprazole, subjects must be medication-free for at least 2 weeks prior to baseline.
• Evidence of hypersensitivity to aripiprazole (defined as an allergic response [e.g., skin rash] or potentially serious adverse effect [e.g., significant tachycardia]).
• 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.