Trial to Evaluate the Long-term Efficacy of Oral Aripiprazole in the Treatment of Pediatric Subjects With Tourette's Disorder

This is a phase 3b/4, randomized, double-blind, placebo-controlled, outpatient trial to
evaluate the long-term efficacy of oral aripiprazole in the treatment of pediatric subjects
with Tourette's Disorder (TD). The trial consists of 3 distinct phases: a pretreatment phase,
open-label stabilization phase, and a double-blind randomized withdrawal phase.

Inclusion Criteria:

- The subject is a male or female child or adolescent, 6 to 17 years of age (inclusive)
at the time of signing the informed consent/assent.

- The subject meets current DSM-5 diagnostic criteria for TD, documented at screening
and made by an adequately trained clinician, as confirmed by the Kiddie Schedule for
Affective Disorders and Schizophrenia - Present and Lifetime Version.

- The subject has a TTS ≥ 20 on the YGTSS at screening and baseline (Day 1).

- The subject, a caregiver, and the investigator must all agree that the presenting tic
symptoms cause impairment in the subject's normal routines, which include academic
achievement, occupational functioning, social activities, and/or relationships.

- Females of childbearing potential (all female subjects ≥ 12 years of age and all
female subjects < 12 years of age if menstruation has started) must have a negative
pregnancy test and must not be pregnant or lactating.

- Written informed consent must be obtained from the subject or a legally acceptable
representative (eg, guardian or caregiver), in accordance with requirements of the
trial site's institutional review board (IRB)/independent ethics committee (IEC) and
local regulatory requirements, prior to the initiation of any protocol-required
procedures. In addition, the subject, as required by the trial center's IRB/IEC, must
provide informed assent at screening and as such must be able to understand that he or
she can withdraw from the trial at any time.

- Ability, in the opinion of the principal investigator, of the subject and the
subject's legally acceptable representative (eg, guardian) or caregiver(s) to
understand the nature of the trial and follow protocol requirements, including the
prescribed dosage regimens, tablet ingestion, and discontinuation of prohibited
concomitant medications, to read and understand the written word in order to complete
subject-reported outcomes measures, and to be reliably rated on assessment scales.

Exclusion Criteria:

- The subject presents with a clinical presentation and/or history that is consistent
with another neurologic condition that may have accompanying abnormal movements. These
include, but are not limited to, the following: Transient tic disorder; Huntington's
disease; Parkinson's disease; Sydenham's chorea; Wilson's disease; Mental retardation;
Pervasive developmental disorder; Tardive dyskinesia; Traumatic brain injury; Stroke;
Restless legs syndrome.

- The subject has a history of schizophrenia, bipolar disorder, or other psychotic
disorder.

- Subjects who receive psychostimulants for the treatment of attention-deficit
hyperactivity disorder (ADHD) and who have developed and/or had exacerbations of the
tic disorder after the initiation of stimulant treatment. (Note that subjects with
ADHD who are treated with psychostimulants and have not developed new tics or a
worsening of their current tics can be included if all other enrollment obligations
are met).

- The subject currently has a primary diagnosis that meets DSM-5 criteria for mood
disorder.

- The subject has severe obsessive-compulsive disease, as evidenced by a Children's
Yale-Brown Obsessive Compulsive Scale (CY-BOCS) score > 16.

- The subject has taken aripiprazole within 1 month (30 days) of the screening visit.

- The subject has a history of neuroleptic malignant syndrome.

- Subject is a sexually active male or female of childbearing potential (FOCBP) (all
female subjects ≥ 12 years of age and all female subjects < 12 years of age if
menstruation has started) who will not agree to practice 2 acceptable methods of birth
control or who will not remain abstinent during the trial and for 30 or 90 days
following the last dose of IMP for females and males, respectively. Abstinence will be
permitted if it is confirmed and documented at every trial visit.

- The subject represents a significant risk of committing suicide based on history
(suicide attempt in past 1 year).

- The subject has a body weight < 16 kg.

- Subjects who have taken neuroleptic or antiparkinson drugs within 14 days prior to
baseline.

- Subjects requiring cognitive-behavioral therapy (CBT) for TD during the trial period.
CBT for other nonexclusionary disorder must remain consistent throught the trial.

- The subject has met DSM-5 criteria for any significant psychoactive substance use
disorder within the past 3 months.

- A positive drug screen for cocaine, alcohol, or other drugs of abuse (excluding
caffeine, nicotine, or prescribed psychostimulants for ADHD). Investigators can choose
to repeat a positive drug screen one time during screening period after concurrence
from the medical monitor. A second positive test for any drug of abuse would be
exclusionary.

- Subject requiring medication not allowed per protocol.

- Use of any cytochrome P450 (CYP)2D6 and CYP3A4 inhibitors or CYP3A4 inducers within 14
days prior to baseline and for the duration of the trial.

- Other nutritional or dietary supplements and nonprescription herbal preparations for
TD (eg, cannabinoids, N-aceytlcysteine, omega-3 fatty acids, kava extracts, GABA
supplements) within 7 days prior to baseline and for the duration of the trial, unless
approved in advance by the medical monitor.

- The inability to swallow tablets or tolerate oral medication.

- Subject has participated in a clinical trial involving either study medication or
interventional (non-medication) treatment for TD within the last 60 days.

- The following laboratory test results, vital signs and electrocardiogram (ECG) results
are exclusionary: Platelets ≤ 75,000/mm^3; Hemoglobin ≤ 9 g/dL; Neutrophils, absolute
≤ 1000/mm^3; Aspartate aminotransferase > 3 × upper limit of normal (ULN) as defined
by the central laboratory; Alanine aminotransferase > 3 × ULN as defined by the
central laboratory; Creatinine ≥ 2 mg/dL; Diastolic blood pressure > 105 mmHg;
Corrected QT interval ≥ 450 msec (males) or ≥ 470 msec (females) using the corrected
QT interval for heart rate using Fridericia's formula