Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia

This was a randomized, double-blind, placebo-controlled study consisting of a screening phase
and 4 treatment phases. Eligibility was determined during a screening phase of 2 to 42 days.
Patients receiving oral treatment with an antipsychotic other than non-generic aripiprazole
entered Phase 1. Patients with a lapse in aripiprazole or other antipsychotic treatment at
the time of study entry ("lapse" defined as > 3 consecutive days without medication) entered
directly into Phase 2. During Phase 1 (oral conversion), patients were cross-titrated during
weekly visits from other antipsychotics to oral non-generic aripiprazole monotherapy over a
minimum of 4 weeks and a maximum of 6 weeks. During Phase 2 (a minimum of 4 weeks and a
maximum of 12 weeks in duration), patients were assessed bi-weekly and stabilized on an oral
dose of aripiprazole ranging from 10 mg to 30 mg daily. After stability criteria were met in
Phase 2, patients entered the single-blind aripiprazole intramuscular (IM) depot
stabilization phase, Phase 3. In Phase 3, patients were stabilized on aripiprazole IM depot
for 12 consecutive weeks. Once the patient met the stability criteria, they were eligible to
be randomized into the double-blind phase, Phase 4. Patients were randomized in a 2:1 ratio
(aripiprazole IM depot vs placebo IM depot) stratified by region and last aripiprazole IM
depot injection dose level in Phase 3. During Phase 4, patients were assessed for impending
relapse/exacerbation of psychotic symptoms. If a patient was identified with impending
relapse/exacerbation of psychotic symptoms, they were withdrawn from the trial and given the
opportunity to enroll into an open-label aripiprazole IM depot trial, 31-08-248. Patients
that completed Phase 4 (up to and including Week 52) had the option to enroll into an
open-label aripiprazole IM depot trial, 31-08-248 (NCT00731549).

Inclusion Criteria:

- Subjects who are able to provide written informed consent and/or consent obtained from
a legally acceptable representative (as required by the Institutional Review
Board/Institutional Ethics Committee [IRB/IEC]), prior to the initiation of any
protocol-required procedures.

- Male and female subjects 18 to 60 years of age, inclusive, at time of informed
consent.

- Subjects with a current diagnosis of schizophrenia as defined by Diagnostic and
Statistical Manual of Mental Disorders, 4th edition text revision (DSM-IV-TR) criteria
and a history of the illness for at least 3 years prior to screening.

- Subjects who, in the investigator's judgment, require chronic treatment with an
antipsychotic medication.

- Subjects able to understand the nature of the study and follow protocol requirements,
including the prescribed dosage regimens, tablet ingestion, IM depot injection,
discontinuation of prohibited concomitant medications; who can read and understand the
written word in order to complete patient-reported outcomes measures; and who can be
reliably rated on assessment scales.

Exclusion Criteria:

- Subjects with a current DSM-IV-TR diagnosis other than schizophrenia, including
schizoaffective disorder, major depressive disorder, bipolar disorder, delirium,
dementia, or amnestic or other cognitive disorders. Also, subjects with borderline,
paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.

- Subjects with schizophrenia that are considered resistant/refractory to antipsychotic
treatment by history or response only to clozapine.

- Subjects with a significant risk of violent behavior or a significant risk of
committing suicide based on history or investigator's judgment.

- Subjects who currently meet DSM-IV-TR criteria for substance dependence, including
alcohol and benzodiazepines, but excluding caffeine and nicotine; or 2 positive drug
screens for cocaine.

- Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment
with aripiprazole or other quinolinones; or hypersensitivity to antipsychotic agents.

- Subjects with uncontrolled thyroid function abnormalities.

- Subjects with a history of seizures, neuroleptic malignant syndrome, clinically
significant tardive dyskinesia, or other medical condition that would expose them to
undue risk or interfere with study assessments.

- Subjects who are involuntary incarcerated.

- Subjects who have used an investigational agent within 30 days of screening or prior
participation in a clinical study with aripiprazole IM depot.

- Subjects with clinically significant abnormalities in laboratory test results, vital
signs, or ECG results; and subjects hospitalized for more than 30 days in the 90 days
prior to Phase 1.

- Subjects who fail to wash-out from prohibited concomitant medications, including the
use of CYP2D6 or CYP3A4 inhibitors or CYP3A4 inducers, antipsychotics, antidepressants
(including monoamine oxidase inhibitors [MAOI}), and mood stabilizers during screening
and/or Phase 1.