Aripiprazole, Abilify Maintena Collaborative Clinical Protocol

This is an open-label, multi-center, longitudinal, within-subject comparison study of the
effects of aripiprazole once monthly on 30-, 90-, and 180-day psychiatric re-hospitalization
rates following hospital discharge in subjects with schizophrenia compared with prior
psychiatric hospitalization rates while on oral antipsychotics.

Prospective subjects will undergo screening for eligibility for entry into the study while
hospitalized for symptoms due to schizophrenia.

Prospective subjects will be hospitalized for the necessary length of time as determined by
the assigned treatment provider as clinically indicated, per the current standard of care.
To be eligible, the anticipated duration of hospitalization should be long enough to
accommodate the screening procedures, the 3-day Oral Tolerability Phase (if applicable), and
initiation of treatment with aripiprazole once monthly.

During the Screening Period, subjects can be treated with any oral antipsychotic medication
of the clinician's choice, with the exception of clozapine and olanzapine. However, oral
olanzapine is permitted during the Screening Period only for subjects who are eligible for
Phase A. Following the Screening Period, subjects who have no history of aripiprazole use
will be entered into Phase A, the Oral Tolerability Phase. Subjects from Phase A that
demonstrate tolerability to aripiprazole will then be entered into Phase B (i.e., the
Treatment Phase). Subjects who already have a history of tolerating at least three
consecutive oral doses of aripiprazole will be entered directly into Phase B. All eligible
subjects will eventually enter Phase B.

Subjects who meet the inclusion and exclusion criteria and have no history of oral
aripiprazole use will enter Phase A after the Screening Period while still hospitalized.
Subjects in Phase A will be administered oral aripiprazole, as indicated in the product
labeling, to determine tolerability. Dosage will be based on symptoms and the judgment of
the investigator. The dose of oral aripiprazole may be titrated as needed. Prior
antipsychotic medications will be tapered off and discontinued during the Screening Period
and Phase A as clinically appropriate.

During Phase A, tolerability to oral aripiprazole will be evaluated daily for a minimum of 3
days using safety and tolerability measures (i.e., AIMS, BARS, and SAS) in conjunction with
clinical judgment. If the subject shows tolerability to the oral aripiprazole, the Phase B
baseline/Day 1 should occur with the first aripiprazole once monthly injection given
immediately after the Phase B baseline/Day1 assessments. If a subject is unable to tolerate
oral aripiprazole during the tolerability assessment in Phase A, he or she will be withdrawn
from the study.

During Phase B, the subject will receive the first aripiprazole once monthly intramuscular
(IM) injection, in conjunction with the first of 14 doses of concomitant oral aripiprazole,
as indicated in the product labeling, after the baseline data are collected.

All subjects must attend scheduled visits at the Baseline Visit and Weeks 2, 4, 8, 12, 16,
20, and 24, totaling 180 days. Aripiprazole once monthly injections will occur at the
Baseline Visit and every 28 ( -2, +5) days at Weeks 4, 8, 12, 16, 20, and 24, totaling seven
injections. After the initial injection of 400 mg, the monthly dosage can be decreased to
300 mg, based on the clinical judgment of the investigator. All aripiprazole once monthly
injections will be administered based on the investigator's judgment and the prescribing
information.

For subjects who are psychiatrically stabilized and discharged prior to the completion of
the required 14-day course of oral aripiprazole, a pre-discharge assignment will be given to
a community support worker (CSW). The CSW will maintain regular contact with the subject
until the first outpatient visit in Phase B (Week 2), when oral aripiprazole will be
discontinued. Regular contact is defined as no less than weekly, but can be more frequent
depending on the clinical judgment of the CSW and outpatient treatment team. Following the
Week 2 Visit, subjects will have contact with their assigned CSW based on routine clinical
care. Contact with the CSW can be in person or by telephone, as clinically appropriate.

Note: All long-acting antipsychotics are excluded from use during the study; however,
aripiprazole once monthly is allowed

Inclusion Criteria:

- Are able to provide written informed consent.

- Are male and female subjects 18 to 65 years of age, inclusive, at time of informed
consent

- Have a current diagnosis of schizophrenia as defined by DSM-5 criteria and a history
of the illness for at least 6 months prior to screening from a reliable source (e.g.,
subject, family member, friend, caregiver, healthcare provider, or medical records)

- Present at one of the selected inpatient units with acute psychotic symptoms for
hospitalization at study entry

- Have a clinically indicated need for a change in current antipsychotic therapy

- Are on Medicaid with searchable claims data

- Have at least one inpatient psychiatric hospitalization or psychiatric ED visit
within the 6 months prior to screening

- Have been previously prescribed oral antipsychotic treatment for the 6 consecutive
months prior to screening

- Have a history of response to antipsychotic treatment, with no history of clozapine
treatment

- Are able to understand the nature of the study and follow protocol requirements,
including the prescribed dosage regimens, tablet ingestion, aripiprazole once monthly
injection, and discontinuation of prohibited concomitant medications

- Are able to read and understand the written word in order to complete
subject-reported outcomes measures

- Are willing to accept a monthly injection

- Are male and female subjects who are surgically sterile (i.e., have undergone
orchiectomy or hysterectomy, respectively); female subjects who have been
postmenopausal for at least 12 consecutive months; or male and female subjects who
agree to use an approved form of birth control during study participation

Exclusion Criteria:

- Has a current DSM-5 diagnosis other than schizophrenia, including schizophreniform
disorder, schizoaffective disorder, major depressive disorder, bipolar disorder,
delirium, dementia, amnestic or other cognitive disorders. Also excluded are subjects
with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial
personality disorder.

- Prisoners or subjects who are involuntarily incarcerated, or have been incarcerated
in the past 7 months for any reason

- Require potent cytochrome P450 (CYP)2D or CYP3A4 inhibitors or CYP3A4 inducers

- Are allergic, intolerant, or unresponsive to prior treatment with aripiprazole or
other quinolinones or has a history of hypersensitivity to antipsychotic agents

- Have received electroconvulsive therapy within the 6 months prior to screening

- Have a history of neuroleptic malignant syndrome or clinically significant tardive
dyskinesia as assessed by the investigator

- Have current diagnosis of diabetes or known fasting triglyceride levels consistent
with risk for pancreatitis

- Meets DSM-5 criteria for current substance use disorder within 3 months prior to
screening

- Received treatment with long-acting injectable antipsychotics (e.g., haloperidol
decanoate, fluphenazine decanoate, risperidone long-acting injection [Risperdal
Consta®], paliperidone palmitate extended-release injectable suspension [Invega®
Sustenna®], olanzapine for extended-release injectable suspension [Zyprexa®
Relprevv™]), in which the last dose was within 7 months prior to screening

- Have a significant risk of committing suicide based on history, routine psychiatric
status examination, investigator's judgment, or who have an answer of "yes" on
Question 4 or Question 5 within the last 30 days on the baseline version of the
C-SSRS

- Have a history or evidence of a medical condition that would expose them to an undue
risk of a significant AE or interfere with assessments of safety or efficacy during
the course of the study, including but not limited to hepatic, renal, respiratory,
cardiovascular, endocrine, neurologic, hematologic, or immunologic disease as
determined by the clinical judgment of the investigator

- Have results from one or more of the following laboratory test, vital sign, and ECG
tests at screening that are exclusionary (laboratory testing and ECGs will be
performed locally): Platelets ≤ 75,000/mm3; Hemoglobin ≤ 9 g/dL; Fasting blood
glucose > 126 mg/dL or HbA1c > 7.0%; Fasting triglyceride > 500 mg/dL; Neutrophils,
absolute ≤ 1000/mm3; Aspartate transaminase (AST) > 3x ULN; Alanine transaminase
(ALT) > 3x ULN; Creatinine ≥ 2 mg/dL; Diastolic blood pressure > 105 mmHg; QTc > 475
msec on either the QTcB (Bazett) or QTcF (Fridericia) corrections on ECG, confirmed
by a second tracing; Any other abnormal laboratory tests, vital sign results, or ECG
findings that, in the judgment of the investigator, are medically significant and
would affect the safety of the subject or the interpretation of the study results.
Abnormal results for laboratory parameters or vital signs should be repeated to
ensure reproducibility of the abnormality before excluding a subject based on the
criteria noted above.

- Have been previously enrolled in an aripiprazole once monthly clinical study

- Have participated in any clinical study with an investigational agent within the past
30 days

- Are pregnant or lactating