A Phase IIIb Multi-Center, Open-Label, Mirror-Image, Trial in Adult Subjects With Schizophrenia Treated Prospectively for 6-months With Abilify MyCite®
Phase: PHASE3
Conditions: Schizophrenia
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Official Title: 
A Phase IIIb Multi-Center, Open-Label, Mirror-Image, Trial in Adult 
Subjects With Schizophrenia Treated Prospectively for 6-months With 
Abilify MyCite®
NCT Number: 
NCT03892889 
Document Date: 
Protocol Version 2.0 : 11 February 2019 

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Protocol Synopsis
Name of Sponsor: Otsuka Pharmaceutical 
Development & Commercialization, Inc.
Name of Investigational Medicinal Product: 
Aripiprazole Digital (OPC-14597-Digital)
Protocol No.: 031-201-00301
IND No.: 115927
Protocol Title:
A Phase IIIb Multi-Center, Open-Label, Mirror-Image, Trial in 
Adult Subjects with Schizophrenia Treated Prospectively for 
6-months with Abilify MyCite®
Clinical Phase:
3b
Treatment Indication: Schizophrenia
Objective(s):
Primary:

To compare inpatient psychiatric hospitalization rates
(proportion of subjects with ≥ 1 inpatient psychiatric
hospitalizations) between the retrospective period
(Months 1 to 3) while subjects are on oral standard-of-care
antipsychotic treatment and the prospective period
(Months 1 to 3) after the subjects switch to Abilify
MyCite.
Secondary:

To evaluate improved adherence of Abilify MyCite based
on overall proportion of days covered (PDC).

To further evaluate long-term safety and tolerability of
Abilify MyCite.
Trial Design:
This is a phase 3b, open-label, prospective, clinical trial 
designed to assess the difference between inpatient psychiatric 
hospitalization rates in subjects on oral standard-of-care 
antipsychotic treatment(s) for a period of 6 months followed 
by a switch to Abilify MyCite for a period of 3 months 
(Months 1 to 3). At the Month 3 visit, the investigator should 
decide if subjects will continue on Abilify MyCite for an 
additional 3 months (Months 4 to 6) or switch to a standard-of-
care treatment (eg, oral atypical antipsychotics or a long acting 
injectable [LAI]) for the duration of treatment.
This trial will include male and female subjects who are 18 to 
65 years of age, inclusive, with a diagnosis of schizophrenia 
according to Diagnostic and Statistical Manual of Mental 
Disorders, Fifth Edition (DSM-5) criteria. Subjects must have 
had at least 1 inpatient psychiatric hospitalization within 
4 years (48 months) and must have been prescribed oral 
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antipsychotics for at least 6 months or longer prior to 
screening.
Subjects will enter a screening period (up to 45 days). If 
deemed eligible to participate, subjects will enter an open-label 
Abilify MyCite treatment prospective phase for up to 
6 months.
Oral Standard-of-Care Antipsychotic Treatment(s) 
(Retrospective Phase)
To be eligible for trial participation, subjects must have been 
prescribed oral antipsychotic standard-of-care 
pharmacotherapy for at least 6 months or longer, with evidence 
of prescription (ie, pharmacy records) during the retrospective 
phase and prior to screening. Subjects administered 
antipsychotics other than aripiprazole must cross-titrate onto 
oral aripiprazole during the screening period at the discretion 
of the investigator to be eligible for trial participation.
Screening
After providing informed consent, subjects will enter the 
45-day (Days -45 to -1; approximately 6 weeks) screening 
period to determine if they are eligible to enter the Abilify 
MyCite treatment (prospective) phase. The subject’s past 
psychiatric history for the 6 months prior to screening must be 
available, inclusive of a comprehensive review of all 
psychiatric hospitalizations and interventions (psychiatric
only).
Subjects who meet the inclusion/exclusion criteria and who are 
receiving antipsychotic medication(s) other than aripiprazole 
and who have no history of tolerating oral aripiprazole may be 
converted to oral aripiprazole monotherapy through 
cross-titration and undergo an assessment of aripiprazole 
tolerability at the discretion of the investigator. Subjects 
currently receiving oral aripiprazole monotherapy, or subjects 
currently taking any antipsychotic other than oral aripiprazole 
and have a history of tolerating oral aripiprazole may enter the 
Abilify MyCite treatment phase directly as long as the 
investigator deems subject safety is maintained and adequate 
psychiatric records are documented.
Abilify MyCite Treatment (Prospective) Phase
For subjects enrolled in the trial, those not on aripiprazole at 
screening and who need to cross-titrate will do so during the 
screening period for conversion to aripiprazole from other 
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antipsychotics according to the approved labels. At the 
baseline visit (Day 1), Abilify MyCite onboarding will be 
provided with informational materials and additional call 
center support. Initiation of Abilify MyCite treatment will 
commence at the baseline (Day 1) visit, with subjects ingesting 
the Abilify MyCite tablet embedded with an ingestible event 
marker (IEM) sensor product, wearing the patch, and using the 
smartphone app for up to 6 months, including a required 
3 months (Months 1 to 3) of Abilify MyCite treatment. This 
will be followed, at investigator discretion, to either change to 
standard-of-care antipsychotic treatment (eg, oral or LAI) or 
remain on Abilify MyCite for the second 3-month period
(Months 4 to 6) during the prospective phase. The first dose of 
Abilify MyCite is to be taken at the baseline (Day 1) visit (in 
the clinic) during onboarding, unless subjects have already 
taken their daily dose. Subjects should not take their oral 
standard-of-care medication that morning before the baseline 
(Day 1) visit.
During the assessment period, subjects will visit the 
investigator for clinical evaluations at baseline (Day 1), 
Month 3, and Month 6/early termination (ET). Monthly 
assessments will follow a 28-day schedule, and at each visit 
and at any unscheduled visits, the subject’s clinical status will 
be evaluated. All hospitalizations and all interventions 
(psychiatric only as well as pharmacy cost of all medications) 
will be recorded, in addition to all other assessments outlined 
in this protocol. The primary endpoint will be assessed at 
Month 3. The final trial visit will be on Month 6/ET and will 
be followed by a 30-day (± 3 day) safety follow-up period for 
subjects continuing on Abilify MyCite. For subjects 
completing Months 4 to 6 on standard of care, a 30-day safety 
follow-up period is not required. Subjects will also visit the 
clinic for medication dispensing and accountability at Months 
1, 2, 4, and 5. Any treatment changes, including reason for the 
change, will be recorded in the electronic case report form
(eCRF).
Evaluation of safety and tolerability of Abilify MyCite as 
assessed by frequency and severity of the adverse events (AEs) 
to be collected in this trial, ie, serious AEs (SAEs), 
device-related nonserious AEs, potential hepatotoxicity cases, 
and pregnancies.
Subject use of the Abilify MyCite system will be monitored by 
their respective investigators, who are suggested to review the 
physician dashboard data at a minimum of every 2 weeks and 
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make changes to current treatment plan and therapy at their 
discretion. The investigators may request that a subject return 
to the site for unscheduled visits as deemed appropriate. In the 
event of an unscheduled visit, review of the investigator
dashboard and safety events will be collected.
Safety Follow-up
All subjects who complete or withdraw from the trial while on 
Abilify MyCite (unless they have withdrawn their consent for 
participation in the trial) will receive a telephone call for safety 
follow-up at 30 days (± 3 days) after the last trial visit.
This telephone contact will be made to assess if there were any 
AEs experienced since the last trial visit. In addition, the 
subject will be asked about any new medications or changes in 
existing medications and the information will be documented.
Subject Population:
The trial population will include male and female subjects, 
18 to 65 years of age, inclusive, with a diagnosis of 
schizophrenia according to DSM-5 criteria. Subjects must have 
had at least 1 inpatient psychiatric hospitalization within 
4 years (48 months) prior to screening. Subjects must have 
been prescribed oral antipsychotic treatment for at least 
6 months or longer prior to screening. Approximately 
493 subjects will be screened in order to enroll 320 subjects 
and complete 224 subjects.
Inclusion/Exclusion 
Criteria:
Inclusion criteria

Subject must be willing and able to give written (signed 
and dated) informed consent, which includes adherence to 
trial requirements and restrictions before enrolling in the 
trial. Subject must be willing to adhere to trial procedures, 
including troubleshooting of the Abilify MyCite 
application (app) by a third party if needed.

Subject must be able to read and understand English.

Male and female subjects 18 to 65 years of age, inclusive, 
at the time of informed consent.

Subjects are deemed appropriate, per investigator
judgment, to use Abilify MyCite and to enter this 
interventional trial.

Subject must possess a smartphone and is familiar with its 
use and is willing to download and interact with the Abilify 
MyCite app, completing all tasks as well as adequately 
operating all devices, as applicable. Caregiver/support 
person or other third party assistance can be utilized
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throughout participation in the trial. However, subjects 
should be encouraged to complete all tasks themselves. At 
the conclusion of the study, the caregiver/support person 
will be asked (where applicable) to provide feedback via 
the Caregiver Involvement Scale. A subject with a 
smartphone that is not compatible with the Abilify MyCite
app will be offered a loaner phone for the trial period.

Subject possesses the capacity to utilize the technology 
interfaces (eg, open and navigate software apps using the 
touch screen) and telephone features of a smartphone 
(Android or iOS). The subject has satisfactory mobile 
phone reception (preferably 3 bars or more or have 
wireless fidelity [Wi-Fi]) at home and/or at work for 
wireless carrier.

Subject is cooperative, able to ingest oral medication, 
willing to complete all aspects of trial, and capable of 
reporting AEs.

Clinical diagnosis of schizophrenia (defined by DSM-5) 
with a Positive and Negative Syndrome Scale (PANSS)
total score between 60-90.

Subjects currently prescribed oral atypical antipsychotic 
medication including aripiprazole or appropriate for 
aripiprazole treatment for 6 months or longer.

Subjects are required to have had an inpatient 
hospitalization for schizophrenia within the last 48 months 
prior to entering the trial.

Subject’s general medical condition such that participation 
in the trial does not pose any additional risk as per 
investigator’s judgment.

Skin on the anterior chest just above the lower edge of the 
rib cage that is free of any dermatological problems (eg,
dermatosis or dermatitis, open wounds, or other skin 
disorders such as warts, rashes, atopic dermatitis, or 
irritations).
Exclusion criteria

Females who are breast-feeding and/or who are pregnant at 
the time of trial enrollment, or who plan to become 
pregnant during the trial.

Sexually active males or women of childbearing potential 
(WOCBP) who do not agree to practice 2 different 
methods of birth control or remain abstinent during the 
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trial and for 30 days after the last dose of Abilify MyCite. 
If employing birth control, 2 of the following precautions 
must be used: vasectomy, tubal ligation, vaginal 
diaphragm, intrauterine device, birth control pill, birth 
control implant, birth control depot injection, condom with 
spermicide, or sponge with spermicide.

Any subject who participated in another clinical trial 
within 30 days of enrollment into the current trial.

Subjects who are currently being treated with an LAI 
antipsychotic or have been treated with an LAI in the 
retrospective 6-month phase.

Subjects with a current DSM-5 diagnosis other than 
schizophrenia, including schizoaffective disorder, bipolar I 
disorder, major depressive disorder (MDD), delirium, 
dementia, amnestic, or other cognitive disorders. Also, 
subjects with borderline, paranoid, histrionic, or antisocial 
personality disorder.

Subject with any disorder including but not limited to 
intellectual developmental delay or disorder, major 
neurocognitive disorder or other condition that may impact 
the subject’s ability to participate in the trial or interact 
with the smartphone application.

Subject who is likely to be incapable of using the Abilify 
MyCite technology, even with assistance.

Subject who has 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 
usability during the course of the trial, including but not 
limited to, hepatic, renal, respiratory, cardiovascular, 
endocrine, neurologic, hematologic, or immunologic 
disease as determined by the clinical judgment of the 
investigator.

Subject with a known allergy to adhesive tape or any 
pertinent components of the patch or aripiprazole tablet 
embedded with an IEM sensor (Abilify MyCite) product.

Any subject who, in the opinion of the investigator or the 
medical monitor, should not participate in the trial.
Trial Site(s):
Approximately 75 sites
Device, Dose, 
Dosage regimen, 
Treatment period, 
Abilify MyCite tracks drug ingestion and is composed of the
following components:

Aripiprazole tablet embedded with an IEM sensor (Abilify 
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Formulation, Mode 
of Administration:
MyCite).

Abilify MyCite Patch (wearable sensor) that detects the 
signal from the IEM sensor after ingestion and transmits 
data to a smartphone.

Abilify MyCite App, a smartphone app, which is used with 
a compatible smartphone to display medication ingestion 
information for the subject.

Web-based portal or dashboard for investigators and 
caregivers.
The treatment medication dose decision will be determined by
the trial investigators independent from the protocol.
Initiation of Abilify MyCite treatment will commence at the 
baseline (Day 1) visit, with subjects ingesting the Abilify 
MyCite tablet embedded with an IEM sensor product, wearing 
the patch, and using the smartphone app for up to 6 months,
including a required 3 months (Months 1 to 3) of Abilify 
MyCite treatment. This will be followed, at investigator 
discretion, to either change to standard-of-care antipsychotic 
treatment (eg, oral or LAI) or remain on Abilify MyCite for 
the second 3-month period (Months 4 to 6), during the 
prospective phase. The first dose of Abilify MyCite is to be 
taken at the baseline (Day 1) visit (in the clinic) during 
onboarding, unless they have already taken their daily dose. 
Subjects should not take their oral standard-of-care medication 
that morning before the baseline (Day 1) visit.
During the assessment period, subjects will visit the 
investigator for clinical evaluations at baseline (Day 1), 
Month 3, and Month 6/ET. Monthly assessments will follow a 
28-day schedule. The primary endpoint will be assessed at 
Month 3. The final trial visit will be on Month 6/ET and will 
be followed by a 30-day (± 3 day) safety follow-up period for 
subjects continuing on Abilify MyCite. For subjects 
completing Months 4 to 6 on standard of care, a 30-day safety 
follow-up period is not required. Subjects will also visit the 
clinic for medication dispensing and accountability on Months 
1, 2, 4, and 5. Any treatment changes, including reason for the 
change, will be recorded in the eCRF.
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Safety Endpoints:
Adverse events will be examined by frequency, severity, 
seriousness, and discontinuation (all cause and due to AEs). 
The safety and tolerability of Abilify MyCite, as assessed by 
the frequency and severity of SAEs, device-related nonserious 
AEs, potential hepatotoxicity cases, and pregnancies will be 
assessed along with an evaluation of any product quality 
complaints that arise. The Columbia Suicide Severity Rating 
Scale (C-SSRS) will be completed at baseline and all 
subsequent visits to assess the risk of suicide events and to 
classify reported suicide events.
Statistical Methods:
The primary endpoint of this trial is the comparison of 
inpatient psychiatric hospitalization rates (proportion of 
subjects with ≥ 1 inpatient psychiatric hospitalization[s]) 
between the retrospective period (Months 1 to 3) while on oral 
standard-of-care antipsychotic treatment and the prospective 
period (Months 1 to 3) after the switch to Abilify MyCite. The 
analysis will be performed using a McNemar test on those who 
have hospitalization data during Months 1 to 3 prior to the 
screening period and during Months 1 to 3 after switch to 
Abilify MyCite.
The sample size calculation assumes that 15.5% of subjects are 
hospitalized during retrospective Month 1 to 3 and 7% are 
hospitalized during prospective Month 1 to 3; about 5% of 
subjects who are not hospitalized retrospective will be 
hospitalized prospective while 13.5% of subjects who are 
hospitalized retrospective will not be hospitalized.
Two interim analyses are planned when 50% and 70% of 
subjects have completed the prospective phase (3 months).
With the above assumption and 2 interim analysis, 
224 completed subjects will provide 80% power and conserve 
the overall Type I error at 0.05 level in order to detect a 
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difference of 8.5% in 2 paired hospitalization proportions 
between retrospective and prospective periods while the 
proportion of total discordant pairs is 18.5%. This sample size 
is based on the 3 sequential tests that are made using 
LanDeMets Spending Function with O’Brien-Fleming 
boundary; a futility conditional power of 15% is built in the 
sample size calculation to allow the trial to stop for futility. 
Based on the conditional power and the alpha level at the 
interim analysis, the trial could stop for efficacy or futility, 
continue with the initial planned 224 sample size or increase to 
up to 300 sample size if the conditional power falls between 
30% and 80% at interim.
The 2-sided alpha levels for these 2 interim analyses are 
0.00312 and 0.0139 respectively, and the alpha left for the 
final analysis will be 0.04528.
In general, baseline measurements of safety variables are 
defined as the last measurements prior to the first dosing of 
Abilify MyCite for the prospective phase of the trial. All safety 
summaries will be descriptive in nature.
Trial Duration:
The duration of this trial from first subject enrolled to first 
subject completed is estimated to be up to approximately 
8.5 months including a 45-day screening period and a 6 month 
prospective phase that includes a required 3 months (Months 1 
to 3) of Abilify MyCite treatment. This will be followed, at 
investigator discretion, to either change to standard-of-care 
antipsychotic treatment (eg, oral or LAI) or remain on Abilify 
MyCite for the second 3-month period (Months 4 to 6), during 
the prospective phase. The final trial visit will be on 
Month 6/ET and will be followed by a 30-day (± 3 day) safety 
follow up period for subjects continuing on Abilify MyCite. 
For subjects completing Months 4 to 6 on standard of care, a 
30-day safety follow-up period is not required. Subjects will 
also visit the clinic for medication dispensing and 
accountability on Months 1, 2, 4, and 5. Any treatment 
changes, including reason for the change, will be recorded in 
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the eCRF. Total length of participation in the trial will vary 
depending on the screening duration and if the subjects remain 
on Abilify MyCite treatment.
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Table of Contents
Protocol Synopsis...........................................................................................2
Table of Contents.........................................................................................14
List of In-text Tables ...................................................................................19
List of In-text Figures..................................................................................20
List of Appendices........................................................................................21
List of Abbreviations and Definitions of Terms .......................................22
1
Introduction ........................................................................................24
1.1
Nonclinical Data................................................................................................27
1.2
Clinical Data......................................................................................................28
1.3
Known and Potential Risks and Benefits ..........................................................28
1.3.1
Risks Related to the Abilify MyCite System..................................................28
1.3.1.1
Skin Findings at the Site of the Patch Attachment......................................28
1.3.1.2
Allergic Reaction ........................................................................................29
1.3.1.3
Changes in Stool Habits..............................................................................29
1.3.1.4
Anxiety from the Use of the Abilify MyCite System .................................29
1.3.1.5
Potential Theoretical Abilify MyCite System-related Risks.......................30
1.3.1.5.1
Procedure-Related Risks .........................................................................30
1.3.1.5.1.1
Communications-related Risks............................................................30
1.3.1.5.1.2
Less Significant Procedure-related Risks ............................................30
1.3.2
Benefits Related to the Abilify MyCite System .............................................30
1.3.2.1
Potential Benefits Related to the Abilify MyCite System ..........................31
2
Trial Rationale and Objectives..........................................................31
2.1
Trial Rationale...................................................................................................31
2.2
Dosing Rationale...............................................................................................32
2.3
Trial Objectives.................................................................................................32
2.3.1
Primary ...........................................................................................................32
2.3.2
Secondary .......................................................................................................32
3
Trial Design.........................................................................................32
3.1
Type/Design of Trial .........................................................................................32
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3.2
Trial Treatments ................................................................................................37
3.2.1
Tolerability Assessment/Cross-Titration........................................................37
3.2.2
Abilify MyCite Treatments.............................................................................38
3.2.2.1
Abilify MyCite Components and Use.........................................................39
3.2.2.2
Abilify MyCite System Onboarding...........................................................40
3.2.2.3
Abilify MyCite System Patch Use..............................................................40
3.3
Trial Population.................................................................................................41
3.3.1
Number of Subjects and Description of Population .......................................41
3.3.2
Subject Selection and Numbering ..................................................................41
3.4
Eligibility Criteria..............................................................................................41
3.4.1
Informed Consent ...........................................................................................41
3.4.2
Inclusion Criteria ............................................................................................42
3.4.3
Exclusion Criteria...........................................................................................43
3.5
Endpoints...........................................................................................................44
3.5.1
Primary Endpoint............................................................................................44
3.5.2
Secondary Endpoint........................................................................................44
3.5.3
Exploratory Endpoints....................................................................................44
3.5.4
Safety Endpoints.............................................................................................45
3.6
Measures to Minimize/Avoid Bias....................................................................45
3.7
Trial Procedures ................................................................................................45
3.7.1
Schedule of Assessments................................................................................51
3.7.1.1
Retrospective Phase (6 Months)..................................................................51
3.7.1.2
Screening Visit............................................................................................51
3.7.1.3
Prospective Phase (6 Months).....................................................................52
3.7.1.3.1
Baseline (Day 1)......................................................................................52
3.7.1.3.2
Months 1 and 2 Visits..............................................................................53
3.7.1.3.3
Month 3 Visit...........................................................................................53
3.7.1.3.4
Months 4 and 5 Visits..............................................................................54
3.7.1.3.5
Month 6/Early Termination Visit ............................................................54
3.7.1.4
Healthcare Utilization Record Evaluation (Month -6 Through Month 
6/ET) ...........................................................................................................55
3.7.1.5
Follow-up....................................................................................................56
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3.7.2
Efficacy Assessments .....................................................................................56
3.7.2.1
Other Trial Assessments .............................................................................56
3.7.2.1.1
Hospitalization.........................................................................................56
56
57
57
57
57
58
58
58
58
.58
3.7.3
Safety Assessments.........................................................................................59
3.7.3.1
Adverse Events............................................................................................59
3.7.3.2
Clinical Laboratory Assessments................................................................59
3.7.3.3
Vital Signs...................................................................................................59
3.7.3.4
Electrocardiogram Assessments..................................................................59
3.7.3.5
Suicidality ...................................................................................................59
3.7.4
End of Trial.....................................................................................................59
3.8
Stopping Rules, Withdrawal Criteria, and Procedures......................................60
3.8.1
Entire Trial......................................................................................................60
3.8.2
Individual Site.................................................................................................60
3.8.3
Individual Subject Discontinuation ................................................................60
3.8.3.1
Treatment Discontinuation..........................................................................60
3.8.3.2
Documenting Reasons for Treatment Discontinuation...............................60
3.8.3.3
Withdrawal of Consent ...............................................................................61
3.9
Screen Failures ..................................................................................................62
3.10
Definition of Completed Subjects.....................................................................62
3.11
Definition of Subjects Lost to Follow-up..........................................................63
3.12
Subject Compliance...........................................................................................63
3.13
Protocol Deviations...........................................................................................63
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4
Restrictions..........................................................................................63
4.1
Prohibited Medications......................................................................................63
4.2
Restricted Medications......................................................................................65
5
Reporting of Adverse Events.............................................................66
5.1
Definitions.........................................................................................................66
5.2
Eliciting and Reporting Adverse Events ...........................................................69
5.3
Immediately Reportable Events ........................................................................69
5.4
Potential Serious Hepatotoxicity.......................................................................70
5.5
Pregnancy..........................................................................................................70
5.6
Procedure for Breaking the Blind......................................................................71
5.7
Follow-up of Adverse Events............................................................................72
5.7.1
Follow-up of Nonserious Adverse Events......................................................72
5.7.2
Follow-up of Serious Adverse Events and Immediately Reportable 
Events .............................................................................................................72
5.7.3
Follow-up and Reporting of Serious Adverse Events and Immediately 
Reportable Events Occurring after Last Scheduled Contact ..........................72
6
Pharmacokinetic Analysis..................................................................73
7
Statistical Analysis..............................................................................73
7.1
Sample Size.......................................................................................................73
7.2
Datasets for Analysis.........................................................................................74
7.3
Handling of Missing Data .................................................................................74
7.4
Primary and Secondary Endpoint Analyses ......................................................74
7.4.1
Primary Endpoint Analysis.............................................................................74
7.4.2
Secondary Endpoint Analysis.........................................................................74
7.4.3
Exploratory Endpoint Analysis.......................................................................75
7.4.4
Interim Analysis..............................................................................................76
7.5
Analysis of Demographic and Baseline Characteristics....................................77
7.6
Safety Analysis..................................................................................................77
7.6.1
Adverse Events ...............................................................................................77
7.6.2
Clinical Laboratory Data ................................................................................78
7.6.3
Vital Signs Data..............................................................................................78
7.6.4
Electrocardiogram Data..................................................................................78
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7.6.5
Suicidality Assessment ...................................................................................78
8
Management of Investigational Medicinal Product........................78
8.1
Packaging and Labeling ....................................................................................78
8.2
Storage...............................................................................................................78
8.3
Accountability ...................................................................................................79
8.4
Returns and Destruction....................................................................................79
8.5
Reporting of Product Quality Complaints.........................................................79
8.5.1
Eliciting and Reporting Product Quality Complaints.....................................80
8.5.2
Information Required for Reporting Purposes ...............................................80
8.5.3
Return Process ................................................................................................80
8.5.4
Assessment/Evaluation...................................................................................80
9
Records Management.........................................................................81
9.1
Source Documents.............................................................................................81
9.2
Data Collection..................................................................................................81
9.3
File Management at the Trial Site.....................................................................82
9.4
Records Retention at the Trial Site....................................................................83
10
Quality Control and Quality Assurance...........................................83
10.1
Monitoring.........................................................................................................83
10.2
Auditing.............................................................................................................83
11
Ethics and Responsibility...................................................................84
12
Confidentiality ....................................................................................84
13
Amendment Policy..............................................................................85
14
Publication Authorship Requirements.............................................85
15
References............................................................................................86
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List of In-text Tables
Table 1-1
Overview of Abilify MyCite System.............................................26
Table 3.2.1-1
Recommendation for Switching from Other Antipsychotic(s) 
to Non-generic Oral Aripiprazole Monotherapy (Trial Drug).......37
Table 3.4.2-1
Inclusion Criteria ...........................................................................42
Table 3.4.3-1
Exclusion Criteria ..........................................................................43
Table 3.7-1
Schedule of Assessments...............................................................48
Table 4.1-1
Example List of CYP3A4 and CYP2D6 Inhibitors and 
CYP3A4 Inducers Prohibited During the Trial .............................64
Table 4.2-1
Medications Restricted During the Trial........................................66
Table 7.4.4-1
Sample Size Re-estimation Schemes.............................................77
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List of In-text Figures
Figure 1-1
Abilify MyCite Components..........................................................26
Figure 3.1-1
Trial Design Schematic..................................................................36
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List of Appendices
Appendix 1
Names of Sponsor Personnel .........................................................89
Appendix 2
Safety Reporting ............................................................................90
Appendix 3
Abilify MyCite Contents................................................................91
Appendix 4
Protocol Amendment .....................................................................92
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List of Abbreviations and Definitions of Terms
Abbreviation
Definition
AE
Adverse event
app
Application
CGI-I
Clinical Global Impression - Improvement of Illness Scale
CGI-S
Clinical Global Impression - Severity of Illness Scale
CRF
Case report form
C-SSRS
Columbia Suicide Severity Rating Scale
CYP
Cytochrome P450
DSM-5
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
ECG
Electrocardiogram
eCRF
Electronic case report form
eICF
Electronic informed consent form
ET
Early termination
FDA
Food and Drug Administration
GCP
Good Clinical Practice
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Council for Harmonisation
ICMJE
International Committee of Medical Journal Editors
ID
Identification
IEM
Ingestible event marker
IND
Investigational new drug
IRB
Institutional review board
IRE
Immediately reportable event
ITT
Intent-to-Treat
LAI
Long-acting injectable
MDD
Major depressive disorder
N or n
Number of subjects
PANSS
Positive and Negative Syndrome Scale
PDC
Proportion of days covered
PQC
Product Quality Complaint
SAE
Serious adverse event
SD
Standard deviation
TEAE
Treatment-emergent adverse event
ULN
Upper limit of normal
Wi-Fi
Wireless fidelity
WOCBP
Women of childbearing potential
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Definition of Terms
Level of Care
Description
Assertive 
Community 
Treatment
Team treatment approach designed to provide comprehensive, community-based 
psychiatric treatment, rehabilitation, and support to persons with serious and 
persistent mental illness such as schizophrenia. Provides highly individualized 
services directly to consumers. Recipients receive the multidisciplinary, round-the-
clock staffing of a psychiatric unit, but within the comfort of their own home and 
community. To have the competencies and skills to meet a client's multiple 
treatment, rehabilitation, and support needs, team members are trained in the areas of 
psychiatry, social work, nursing, substance abuse, and vocational rehabilitation. The 
assertive community treatment team provides these necessary services 24 hours per
day, 7 days per week, and 365 days per year.
Emergency Room 
Visit
Medical treatment facility, specializing in acute care of subjects who present without 
prior appointment, either by their own means or by ambulance. Due to the unplanned 
nature of subject attendance, the department must provide initial treatment for a 
broad spectrum of illnesses and injuries, some of which may be life-threatening and 
require immediate attention. The medical condition may require inpatient admission 
or release back to the community for ongoing outpatient treatment.
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1
Introduction
Abilify MyCite® (aripiprazole tablets with sensor) is a drug-device combination product 
comprised of aripiprazole tablets embedded with an ingestible event marker (IEM) sensor 
intended to track drug ingestion that is indicated for1:

Treatment of adults with schizophrenia.

Treatment of bipolar I disorder:

Acute treatment of adults with manic and mixed episodes as monotherapy and as 
adjunct to lithium or valproate.

Maintenance treatment of adults as monotherapy and as adjunct to lithium or 
valproate.

Adjunctive treatment of adults with major depressive disorder (MDD).
Abilify MyCite tracks drug ingestion and is composed of the following components1:

Aripiprazole tablet embedded with an IEM sensor (Abilify MyCite).

Abilify MyCite Patch (wearable sensor) that detects the signal from the IEM sensor 
after ingestion and transmits data to a smartphone.

Abilify MyCite App, a smartphone application (app), which is used with a compatible 
smartphone to display medication ingestion information for the subject.

Web-based portal or dashboard for investigators and caregivers.
This trial will utilize the clinical supply of Abilify MyCite.
The Abilify MyCite system has been tested in subjects with serious mental illness, with 
clinical trials demonstrating an ability to report tablet ingestion with high accuracy and 
acceptable latency time, with positive results regarding usability reported by both 
subjects and investigators/caregivers.2,3,4,5,6,7,8,9,10
Food and Drug Administration (FDA) approval of Abilify MyCite was also based, in 
part, on evidence from human factors engineering studies, which were conducted to 
ensure safe and effective use of the system.11 Future studies to assess ability to monitor 
and improve adherence and other clinical outcomes will be important.
The Abilify MyCite system is a drug-device combination product comprised of 
aripiprazole (an atypical antipsychotic) tablets embedded with a sensor that 
communicates with a patch (wearable sensor) and a medical software application with 
collected information (ingestion, mood, activity, rest) tracked and summarized for 
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subjects, investigators, and potentially caregivers. Abilify MyCite is intended to track 
drug ingestion and is indicated for the treatment of adults with schizophrenia, bipolar I 
disorder (acute treatment of adults with manic and mixed episodes or maintenance 
treatment of adults), and adjunctive treatment of adults with MDD.1 Abilify MyCite can 
provide objective subject data with regard to medication-taking behaviors and activities 
that can enable clinicians to make more informed and optimal therapeutic decisions. 
Additionally, the Abilify MyCite system allows subjects to engage in taking a more 
active role in their personal wellbeing. The Abilify MyCite system fulfills an unmet need 
regarding medication adherence monitoring in these subjects.
Currently available methods for monitoring adherence have limitations; as such, an 
unmet need exists for a simple, accurate solution for adherence monitoring to enable 
investigators to objectively measure whether a subject was adherent to treatment. 
Increasing investigator awareness of subject nonadherence and its role in suboptimal 
response may allow for better treatment decision making and allow an opportunity for 
more investigator/subject engagement in care. The available evidence suggests that 
subject engagement or activation in serious mental illness, while not a main focus in 
clinical practice, may provide substantial benefit to subject health outcomes, including 
management of comorbid conditions, and should be encouraged.
The Abilify MyCite system may be used by investigators who desire accurate, timely, 
and objective measures of medication adherence over a defined period of time to aid in 
their treatment decisions. It also allows investigators to make treatment decisions based 
on objective medication ingestion data, rather than guessing whether suboptimal response 
is based on poor adherence or limited effectiveness. For subjects, Abilify MyCite offers 
access to objective personal data on medication-taking behaviors and other measures 
such as self-reported mood over time and activity and rest patterns. This healthcare 
information is then available to both the subject and investigator (and caregivers with 
subject consent), which may aid in increased health awareness and more informed shared 
decision making regarding treatment.
Although a large number of pharmacological treatments exist, the management of serious 
mental illness presents a significant personal and societal burden. For treatments to be 
effective, the subject must be adherent to their medication. Although many methods are 
used to measure adherence, studies have shown widespread nonadherence in psychiatric 
populations. Cramer and Rosenheck found average adherence rates of 58% and 65% for 
antipsychotics and antidepressants, respectively, compared with an adherence rate of 76% 
for nonpsychiatric medications.12 This finding is problematic due to the relationship 
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between nonadherence and disease burden. Consequently, nonadherence to psychiatric 
medications remains a major barrier to achieving optimal health outcomes in this 
population and ensuring medication compliance is an unmet medical need.12,13
The components of Abilify MyCite are shown in Figure 1-1 and an overview of the 
Abilify MyCite system is shown in Table 1-1.
Figure 1-1
Abilify MyCite Components
Table 1-1
Overview of Abilify MyCite System
Characteristic
Description
Components

Aripiprazole tablet embedded with an IEM sensor (Abilify MyCite).

Abilify MyCite Patch (wearable sensor) that detects the signal from the IEM 
sensor after ingestion and transmits data to a smartphone.

Abilify MyCite App (a smartphone app which is used with a compatible 
smartphone to display information for the subject).

Web-based portal for investigators and caregivers.
FDA-approved 
indication

A drug-device combination product comprised of aripiprazole tablets embedded 
with an IEM sensor intended to track drug ingestion that is indicated for the 
treatment of adults with schizophrenia; treatment of bipolar I disorder (including 
acute treatment of adults with manic and mixed episodes as monotherapy and as 
adjunct to lithium or valproate, or as maintenance treatment of adults as 
monotherapy and as adjunct to lithium or valproate); and adjunctive treatment of 
adults with MDD.
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Table 1-1
Overview of Abilify MyCite System
Characteristic
Description
Limitations of use

The ability of Abilify MyCite to improve subject compliance or modify 
aripiprazole dosage has not been established.

The use of Abilify MyCite to track drug ingestion in “real-time” or during an 
emergency is not recommended because detection may be delayed or not occur.
The Abilify MyCite system includes an ingestible sensor to confirm ingestion of Abilify 
MyCite when the sensor is activated in the stomach. The sensor activation signal and the 
information about medication ingestion and other physiological metrics are gathered by a 
compatible wearable sensor that relays that information to a mobile app for the subject
and to web-based software that can display information for an investigator or caregiver. 
The Abilify MyCite system is composed of the following components (Figure 1-1 and 
Table 1-1)1,2:

Aripiprazole tablet embedded with an IEM sensor (Abilify MyCite). The IEM is a 
1 mm sized ingestible device embedded in the Abilify MyCite tablet. Upon contact 
with gastric fluid, magnesium and cuprous chloride within the IEM react to activate 
and power the device. The IEM then communicates to the Abilify MyCite Patch 
(wearable sensor) to track aripiprazole ingestion.

Abilify MyCite Patch (wearable sensor) that is designed to detect the ingestion of the 
Abilify MyCite tablet, record the ingestion of the IEM, and transmit ingestion data to 
the mobile subject application. These data include the date and time of ingestion and 
the unique identification number of the ingestible device. The patch also records 
physiological metrics (activity level via step count and body position) and transmits 
these data to a compatible mobile device.

Abilify MyCite App (a smartphone app which is used with a compatible smartphone 
to display information for the subject) to allow subjects to review their medication 
ingestion as well as enter their behavioral data (subject rated mood and quality of 
rest). These data can be shared with investigators and caregivers with the subject’s 
consent.

Web-based portal for investigators and caregivers provides an interface to review data 
shared by a subject.
1.1
Nonclinical Data
Please refer to the Investigator’s Brochure (IB) for more detailed information regarding 
nonclinical data.14
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1.2
Clinical Data
Please refer to the IB for more detailed information.14
1.3
Known and Potential Risks and Benefits
1.3.1
Risks Related to the Abilify MyCite System
1.3.1.1
Skin Findings at the Site of the Patch Attachment
The most common adverse events (AEs) associated with the patch in previous trials have 
been related to skin irritation at the site of the patch placement. This phenomenon has 
generally been mild in intensity, involving itching, localized redness, small papules, 
and/or elevation of the skin under or at the edges of the adhesive. Fine scabbing at the 
edges of the patch occurred rarely without significant ulceration. The mechanism of these 
skin changes, which are transient in nature, is related to irritant contact dermatitis, a 
nonimmune-mediated phenomenon that is commonly seen with adhesive medical 
products, arising from mechanical irritation, chemical irritation, and decreased 
breathability of the skin under the patch. In a small number of cases, irritant contact 
dermatitis leads to transient discoloration of the skin that may last weeks to months.
Several mitigations will be implemented to reduce the risk of these hazards. From a 
materials standpoint, the patch has been designed and manufactured under Good 
Manufacturing Practices from components and medical-grade materials that have 
individually passed required biocompatibility testing. These facts underpin a favorable 
biocompatibility assessment of the patch.
Skin will be monitored for irritation or changes at the site(s) of patch placement by the 
investigators during investigator visits. Subjects will be trained to self-monitor their skin 
at the sites of patch placement between investigator visits. The patches will be replaced 
during the trial. Should skin changes arise, then the simplest intervention will be to move 
the patch to a different site on the torso. Subjects will also be told that they are free to 
remove the patch at any time, and that if they do they must inform trial staff immediately. 
Subjects whose frequency or intensity of skin changes is unacceptable can be withdrawn 
from the trial by the investigators.
Finally, since the patch has an adhesive backing for long-term wear, some skin irritation 
may result from removing the patch because it retains a significant amount of adhesion. 
To reduce this possibility, subjects may be provided adhesive remover wipes, which can 
be used to ease any discomfort from patch removal. If the patch falls off, the subject 
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should replace it with another available patch and inform the site staff. Abilify MyCite is 
not expected to add any appreciable risk to the inherent risks of the trial population.
1.3.1.2
Allergic Reaction
An allergic reaction could potentially arise from exposure to components of Abilify 
MyCite product or the patch, including the following: Adhesive on the patch; microchip 
of the IEM; minerals of the IEM; excipient materials in the IEM and IEM tablet dose 
forms; excipient materials in the IEM formulations; and/or dyes used in the IEM 
formulations.
To mitigate the risk of this potential hazard, prospective subjects who have a known 
allergy to any of the components listed above will be excluded from the trial. Allergy to 
tape will be specifically queried. Trial subjects will be monitored for symptoms and signs 
of allergic reaction throughout the course of the trial. If symptoms should arise, the 
subject will be treated promptly and accordingly.
1.3.1.3
Changes in Stool Habits
The majority of the excipient materials used in the Abilify MyCite product (and internal 
components of the IEM formulations) are cellulose-based. Cellulose in high oral doses is 
commonly used as a stool softener. Stool softeners typically increase the bulk and 
potentially the frequency of bowel movements, but they rarely cause diarrhea. However, 
the quantities of cellulose-based excipients in a daily dose of Abilify MyCite product in 
this trial are several fold smaller than the therapeutic dose used for stool-softening 
purposes.
Therefore, it is the opinion of the sponsor that the probability of changes in stool habits is 
low and, were they to occur, the clinical implications would likely be minor.
1.3.1.4
Anxiety from the Use of the Abilify MyCite System
Subjects may experience anxiety related to swallowing the Abilify MyCite product, 
wearing the patch, or using the smartphone. Moreover, it is theoretically possible that 
subjects could feel uncomfortable with the concept of 24-hour data collection. To reduce 
potential subject anxiety, adequate training time along with clinical and technical support 
will be made readily available during the trial. Moreover, familiarity with a smartphone is 
an inclusion criterion (see Section 3.4.2).
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1.3.1.5
Potential Theoretical Abilify MyCite System-related Risks
1.3.1.5.1
Procedure-Related Risks
1.3.1.5.1.1
Communications-related Risks
Subjects will be required to use a mobile smartphone during the trial to upload and later 
to view data. Through misapprehension of the use instructions or technical failures, 
subjects could experience confusion or frustration.
To mitigate this problem, only the subjects who have the capacity to utilize the 
technology interfaces (eg, open and navigate software applications using the touch 
screen) and telephone features of a smartphone will be enrolled in this trial.
Moreover, subject privacy is essential. It is theoretically possible that in the process of 
communicating through the app, privacy could become compromised. This could occur 
when data are being transmitted by the app.
To mitigate this risk, industry-standard encryption protocols will be used for data 
transmission from the patch to the computing device and from the computing device to 
the server via the cellular network. The access information for the app data are stored 
only on the sponsor’s servers, which are also protected with industry-standard security 
features.
All aspects of the app are compliant to Health Insurance Portability and Accountability 
Act of 1996 requirements and European General Data Protection Regulation.
Therefore, it is the opinion of the sponsor that the risk of adverse clinical consequences 
from the planned trial communications is very low.
1.3.1.5.1.2
Less Significant Procedure-related Risks
Subjects may feel uncomfortable about answering personal health questions. The risks 
are very unlikely to result in significant adverse clinical outcomes, but research personnel 
will be sensitive to this issue.
1.3.2
Benefits Related to the Abilify MyCite System
There is a potential benefit from participating in the trial, in that subjects may have a 
better understanding of their medication-taking pattern and the relationship to their 
illness. In addition, subjects may have a better understanding of their personal 
physiologic status (eg, activity, rest) by viewing the individualized health data on their 
smartphone.
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The sponsor’s intent is to develop a system that will be of significant benefit to future 
subjects by providing a novel, convenient method to track medication-taking behavior in 
an objective manner, and to monitor important physiologic parameters on an ambulatory 
basis. The execution of the present trial would represent an opportunity to gather 
feedback regarding the use of the app in the trial population. Thus, data gathered in the 
trial will be important for refining the app to help future subjects who may use the 
system.
1.3.2.1
Potential Benefits Related to the Abilify MyCite System
The Abilify MyCite product includes an app providing an advance on the available proxy 
measured by the following:

Ability to provide confirmation of medication ingestion thereby enabling accurate 
detection of subject adherence status.

Ability to provide information to assess whether uncontrolled symptoms may be 
explained by nonadherence or indicate treatment nonresponse.

Ability to assess adherence on a continuous (near real-time) basis.

Ability to provide adherence electronic feedback to subject, investigator, and/or 
caregiver/support person (if applicable).
The sponsor’s intent is to develop a system that will benefit future subjects by providing 
the ability to track their medication-taking behavior in an objective manner and being 
able to monitor several physiologic parameters.
2
Trial Rationale and Objectives
2.1
Trial Rationale
Poor adherence to medication is a major barrier to the treatment of psychiatric disorders. 
Mobile health and digital medicine technologies have become available to subjects and 
consumers that may improve health management and medication compliance.15
Therefore, Otsuka Pharmaceutical Co., Ltd (Otsuka) has developed Abilify MyCite to 
track drug ingestion. Each aripiprazole tablet is embedded with an IEM. When 
swallowed, and after reaching the stomach, the IEM transmits a signal that is detected 
and recorded by a patch worn on the subject’s torso. The patch transmits data to the 
subject’s mobile device (ie, smartphone), which uploads data to a secure, cloud-based 
server. Use of Abilify MyCite will allow subjects to view their aripiprazole ingestion data 
on their mobile device; in this way, the subject can learn about their medication ingestion 
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patterns, which could enable greater subject awareness and self-management of their 
disease.
In addition, the subject’s investigators and elected caregivers can view data via a web-
based portal served by the cloud-based server.1 With Abilify MyCite tracking drug 
ingestion, psychiatric hospitalizations should be reduced when compared to standard-of-
care antipsychotic treatment; this reduction is anticipated to be driven by an improvement 
in timely and appropriate treatment decisions based on objective data. Therefore, use of 
Abilify MyCite is expected to reduce overall healthcare utilization.
2.2
Dosing Rationale
The subjects in this trial will receive Abilify MyCite as dispensed by their investigator.
The treatment medication decision will be determined by the investigators and 
independent from the protocol.
2.3
Trial Objectives
2.3.1
Primary
To compare inpatient psychiatric hospitalization rates (proportion of subjects with 
≥1 inpatient psychiatric hospitalizations) between the retrospective period (Months 1 to 
3) while subjects are on oral standard-of-care antipsychotic treatment and the prospective 
period (Months 1 to 3) after the subjects switch to Abilify MyCite.
2.3.2
Secondary
To evaluate improved adherence of Abilify MyCite based on overall proportion of days 
covered (PDC).
To further evaluate long-term safety and tolerability of Abilify MyCite.
3
Trial Design
3.1
Type/Design of Trial
This is a phase 3b, open-label, prospective, clinical trial designed to assess the difference 
between inpatient psychiatric hospitalization rates in subjects on oral standard-of-care 
antipsychotic treatment(s) for a period of 6 months followed by a switch to Abilify 
MyCite for a period of 3 months (Months 1 to 3). At the Month 3 visit, the investigator 
should decide if subjects will continue on Abilify MyCite for an additional 3 months
(Months 4 to 6) or switch to a standard-of-care treatment (eg, oral atypical antipsychotics 
or a long acting injectable [LAI]) for the duration of treatment.
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This trial will include male and female subjects who are 18 to 65 years of age, inclusive, 
with a diagnosis of schizophrenia according to Diagnostic and Statistical Manual of 
Mental Disorders, Fifth Edition (DSM-5) criteria. Subjects must have had at least 
1 inpatient psychiatric hospitalization within 4 years (48 months) and must have been 
prescribed oral antipsychotics for at least 6 months or longer prior to screening.
Subjects will enter a screening period (up to 45 days). If deemed eligible to participate, 
subjects will enter an open-label Abilify MyCite treatment prospective phase for up to 
6 months.
Oral Standard-of-Care Antipsychotic Treatment(s) (Retrospective Phase)
To be eligible for trial participation, subjects must have been prescribed oral 
antipsychotic standard-of-care pharmacotherapy for at least 6 months or longer, with 
evidence of prescription (ie, pharmacy records) during the retrospective phase and prior 
to screening. Subjects administered antipsychotics other than aripiprazole must cross-
titrate onto oral aripiprazole during the screening period at the discretion of the 
investigator to be eligible for trial participation.
Screening
After providing informed consent, subjects will enter the 45-day (Days -45 to -1; 
approximately 6 weeks) screening period to determine if they are eligible to enter the 
Abilify MyCite treatment (prospective) phase. The subject’s past psychiatric history for 
the 6 months prior to screening must be available, inclusive of a comprehensive review of 
all psychiatric hospitalizations and interventions (psychiatric only).
As safety of the subject dictates, 2 options are available to the investigator as subjects 
transition from the screening period to the Abilify MyCite treatment (prospective) phase: 
1) Antipsychotic medications other than oral aripiprazole may be tapered off and/or 
discontinued during the screening period prior to the subject receiving the first 
treatment with Abilify MyCite.
2) Antipsychotic medications other than oral aripiprazole may be continued during 
the screening period and cross-titration with oral aripiprazole trial drug may 
occur. Some investigators may choose this option for the subject depending as 
local practice patterns dictate and on the subject’s safety (see Section 3.2.1).
Abilify MyCite treatment (prospective) phase
For subjects enrolled in the trial, those not on aripiprazole at screening and who need to 
cross-titrate will do so during the screening period for conversion to aripiprazole from 
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other antipsychotics according to the approved labels. At the baseline visit (Day 1), 
Abilify MyCite onboarding (see Section 3.2.2.2) will be provided with informational 
materials and additional call center support. Initiation of Abilify MyCite treatment will 
commence at the baseline (Day 1) visit, with subjects ingesting the Abilify MyCite tablet 
embedded with an IEM sensor product, wearing the patch, and using the smartphone app 
for up to 6 months, including a required 3 months (Months 1 to 3) of Abilify MyCite
treatment. This will be followed, at investigator discretion, to either change to oral 
standard-of-care antipsychotic treatment (eg, oral or LAI) or remain on Abilify MyCite 
for the second 3-month period (Months 4 to 6), during the prospective phase. The first 
dose of Abilify MyCite is to be taken at the baseline (Day 1) visit (in the clinic) during 
onboarding, unless they have already taken their daily dose. Subjects should not take 
their oral standard-of-care medication that morning before the baseline (Day 1) visit.
During the assessment period, subjects will visit the investigator for clinical evaluations 
at baseline (Day 1), Month 3, and Month 6/early termination (ET). Monthly assessments 
will follow a 28-day schedule, and at each visit and at any unscheduled visits, the 
subject’s clinical status will be evaluated. All hospitalizations and all interventions 
(psychiatric only as well as pharmacy cost of all medications) will be recorded, in 
addition to all other assessments outlined in this protocol. The primary endpoint will be 
assessed at Month 3. The final trial visit will be on Month 6/ET and will be followed by a 
30-day (± 3 day) safety follow-up period for subjects continuing on Abilify MyCite. For 
subjects completing Months 4 to 6 on standard of care, a 30-day safety follow-up period 
is not required. Subjects will also visit the clinic for medication dispensing and 
accountability at Months 1, 2, 4, and 5. Any treatment changes, including reason for the 
change, will be recorded in the electronic case report form (eCRF).
Evaluation of safety and tolerability of Abilify MyCite as assessed by frequency and 
severity of the AEs to be collected in this trial, ie, serious AEs (SAEs), device-related 
nonserious AEs, potential hepatotoxicity cases, and pregnancies.
Subject use of the Abilify MyCite system can be monitored by their respective 
investigators, who are suggested to review the physician dashboard data at a minimum of 
every 2 weeks and make changes to current treatment plan and therapy at their discretion. 
The investigators may request that a subject return to the site for unscheduled visits as 
deemed appropriate. In the event of an unscheduled visit, review of the investigator
dashboard and safety events will be collected.
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Safety Follow-up
All subjects who complete or withdraw from the trial while on Abilify MyCite (unless 
they have withdrawn their consent for participation in the trial) will receive a telephone 
call for safety follow-up at 30 days (± 3 days) after the last trial visit.
This telephone contact will be made to assess if there were any AEs experienced since 
the last trial visit. In addition, the subject will be asked about any new medications or 
changes in existing medications and the information will be documented. The trial design 
is presented in Figure 3.1-1.
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Figure 3.1-1
Trial Design Schematic
Note: Monthly assessments will follow a 28-day schedule.
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3.2
Trial Treatments
3.2.1
Tolerability Assessment/Cross-Titration
Subjects who have no history of tolerating oral aripiprazole will be assessed for 
tolerability to oral aripiprazole or be cross-titrated to oral aripiprazole at the discretion of 
the investigator. The recommended procedure for initiation of oral aripiprazole is an 
ascending cross-titration scheme according to consensus guidelines from a 
multidisciplinary panel16,17 and the procedure as it pertains to this protocol is 
summarized in Table 3.2.1-1.
Table 3.2.1-1
Recommendation for Switching from Other Antipsychotic(s) to 
Non-generic Oral Aripiprazole Monotherapy (Trial Drug)
First 
Weeka
Second 
Weekb
Third 
Week
Fourth 
Week
Fifth 
Week
Sixth 
Week
Non-generic 
aripiprazole dose 
(trial drug)
Initially 5 mg,
increasing to 10 mg
10 mg
10 or 
15 mg
10 or 
15 mg
10 or 
15 mg
10 or 
15 mgc
Dose of other
antipsychotic(s)
No change
No change
Decrease
Decrease 
or D/Cd
Decrease 
or D/Cd
D/Cd
D/C = discontinue
aAdd short-term concomitant medications as needed to control symptoms (eg, agitation, insomnia, and 
nausea).
bGradually withdraw concomitant medications.
cMonotherapy with oral aripiprazole will begin no later than Week 6. The target starting dose for 
monotherapy may be > 15 mg, depending on investigator judgment and the subject’s clinical need.
dThe other antipsychotic treatment(s) can be discontinued at Week 4 or any time thereafter up to, and 
including, Week 6. The subject will enter the oral stabilization phase the day after discontinuation of 
all other antipsychotic treatment(s), or after a minimum of one cycle plus 14 days has elapsed if the 
subject received an approved long-acting antipsychotic treatment prior to enrollment (eg, 2-week 
cycle plus an additional 14 days for risperidone long-acting injection) or 60 days have elapsed for 
investigational long-acting antipsychotics.
The following subjects may proceed directly to the Abilify MyCite treatment 
(prospective) phase without prior cross-titration to oral aripiprazole at the discretion of 
the investigator:

Subjects receiving oral aripiprazole monotherapy at screening, or

Subjects currently taking any antipsychotic other than oral aripiprazole at screening 
and have a history of tolerating oral aripiprazole.
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The purpose of the tolerability assessment/cross-titration is to evaluate for potential 
allergy to aripiprazole and the subject’s clinical status prior to Abilify MyCite treatment. 
Subjects will be seen in the clinic for up to 45 days, until tolerability to oral aripiprazole 
has been determined, based on investigator discretion, or until the subject is terminated 
from the trial.
The recommended initial dose of oral aripiprazole is 10 mg or 15 mg/day, depending on 
the subject’s symptoms and the investigator’s judgment. The investigator may titrate the 
dose of oral aripiprazole up to 30 mg/day as deemed appropriate. Some investigators may 
choose this option for the subject depending as local practice patterns dictate and on the 
subject’s safety.
Subjects may proceed to the Abilify MyCite treatment (prospective) phase after 1 week if 
they tolerate oral aripiprazole according to the investigator’s judgment.16,17 If a subject 
cannot tolerate oral aripiprazole, or requires inpatient psychiatric hospitalization based on 
the investigator’s clinical judgment, the subject will be withdrawn from the trial.
Subjects who routinely take their oral aripiprazole in the morning are not to take the oral 
dose on the morning of clinic visits, so that adjustments to the dose can be made, as 
required. Oral aripiprazole will be administered at the clinic after all assessments have 
been completed.
3.2.2
Abilify MyCite Treatments
The subjects will receive Abilify MyCite as prescribed by their investigators. The subject 
and the investigator will initiate the system at the baseline (Day 1) visit and use it for up 
to 6 months, including a required 3 months (Months 1 to 3) of Abilify MyCite treatment. 
This will be followed, at investigator discretion, to either change to standard-of-care 
antipsychotic treatment (eg, oral or LAI) or remain on Abilify MyCite for the second 
3-month period (Months 4 to 6) during the prospective phase. The first dose of Abilify 
MyCite is to be taken at the baseline (Day 1) visit (in the clinic) during onboarding
(Section 3.2.2.2), unless they have already taken their daily dose. Subjects should not 
take their oral standard-of-care medication that morning before the baseline (Day 1) visit. 
Following this period, the use of Abilify MyCite will be stopped and the subject will 
return to standard-of-care (routine follow-up from care teams and continue standard-of-
care medications). Subjects will have access to their trial account or data in the 
smartphone app until 1 month after the last subject’s Month 6/ET visit. After this 
duration, the subjects will no longer have access to their data.
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Subjects will also visit the clinic for medication dispensing and accountability during the 
prospective phase at Months 1, 2, 4, and 5. Any treatment changes, including reason for 
the change, will be recorded in the eCRF.
3.2.2.1
Abilify MyCite Components and Use
Abilify MyCite includes a drug-device combination of an aripiprazole tablet embedded 
with an IEM sensor product, a patch, and an application software to convey level of 
activity and rest, and to mark events through the act of ingestion.
The patch is a separate compatible medical device, which consists of a wearable sensor 
and an associated compatible medical device software application. The patch is an 
unmedicated adhesive device that is worn within a specified torso area on the left side. 
The patch detects and time-stamps each IEM ingestion as well as measures and records 
other date- and time-stamped physiologic and behavioral data, such as heart rate, physical 
activity (ie, step count), and amount of rest. The patch connects wirelessly to a 
commercially available mobile computing device (ie, smartphone) to transfer data 
captured by the patch via the compatible medical device software application to a secure 
server for aggregation and processing.
The software application, which include elements that reside both locally (eg, on a 
mobile computing device) and remotely (eg, on remote server), enable data transfer and 
display on the subject’s mobile computing device (ie, smartphone) and on the physician 
web-based dashboard. As part of the software application, subjects may enter their 
subjective rest quality on a daily basis and their subjective mood rating up to several 
times a day.
Subjects should own a commercially available smartphone and be familiar with its use. A 
subject with a smartphone that is not compatible with the Abilify MyCite app will be 
offered a loaner phone for the trial period. The smartphone should be charged daily 
(however, it is noted that if the smartphone battery becomes fully depleted, the 
application data will not be lost, as the data will remain stored on the patch). Subjects will 
be requested to carry the smartphone with them as much as possible, and to plug in the 
device at a dedicated location at home where they have easy and frequent access when 
not being carried. The preferred location is on a bedside table or location immediately 
adjacent to where the subject sleeps.
The subject may view his/her data at will on the smartphone. In addition, the subject’s 
selected investigators and selected caregivers/support person (if applicable) can view this 
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information via the cloud-based server. Investigators can set up missed dose notifications 
to monitor any lapses in subject’s adherence.
Each investigator will be provided with a printed Abilify MyCite application reference 
guide that will provide explicit directions for normal use and troubleshooting. At each 
visit, subjects will be reminded by the investigator to contact the call center with any 
technical questions about the application. If there are any technical issues with the 
application that the call center is unable to resolve, the subject will be routed to a 
technology support representative. If a subject contacts the call center with clinical issues 
including reporting of SAEs, the call center will document the event and forward the 
information to the trial site for additional follow-up, as needed.
3.2.2.2
Abilify MyCite System Onboarding
Onboarding involves the pairing of a patch with the application contained on a 
smartphone and then applying that patch to the skin in the proper location.
During the Abilify MyCite onboarding process, the smartphone app will provide 
guidance for skin preparation and patch placement. A simple skin preparation procedure, 
consisting of gently cleaning the skin surface and allowing the area to dry, is 
recommended. On some subjects, clipping of body hair in the placement zone may be 
required to allow secure device adhesion. Placement of the patch should avoid locations 
below the bottom of the rib cage or areas where the patch was previously worn. Use of 
lotions on the skin where the patch will be place is not recommended. The patch can be 
worn during regular activities including showering, but new patches should not be 
applied for a few hours after showering or other physical activities to ensure the adhesive 
sticks properly. The smartphone app will remind subjects when the patch needs to be 
changed.
3.2.2.3
Abilify MyCite System Patch Use
Throughout the assessment period, the subject will be notified by the smartphone app 
when the patch needs to be changed. No patch should remain applied to a subject’s skin 
for longer than the intended patch duration.
Following the initial patch pairing and placement during the baseline visit, a subject will 
be instructed to wear a patch continuously (eg, 24 hours per day, 7 days per week), if 
possible. The patch can be worn throughout different daily activities, including bathing 
and swimming.
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A subject will be told that it is allowable to remove the patch for any reason (especially 
for evidence of local skin irritation/inflammation), but that it is preferred that the patch be 
kept on as much as is tolerable and safe. The subject should note, as much as possible, the 
events surrounding any premature removal of the patch and contact the site immediately.
A reason must be recorded for every patch removal, including reasons for premature 
patch removal, in the eCRF. Subjects are free to replace a patch offsite using dispensed 
trial supplies.
Each subject will return all supplies, including all used patches and associated labels, to 
the trial site. At the end of the trial (Month 6/ET visit), all returned patches and associated 
labels will be destroyed at the trial site(s) or by a designated agent.
3.3
Trial Population
The trial population will include male and female subjects, 18 to 65 years of age, 
inclusive, with a diagnosis of schizophrenia according to DSM-5 criteria. Subjects must 
have had at least 1 inpatient psychiatric hospitalization within 4 years (48 months) prior 
to screening. Subjects must have been prescribed oral antipsychotic treatment for at least 
6 months or longer prior to screening. Approximately 493 subjects will be screened in 
order to enroll 320 subjects and complete 224 subjects.
3.3.1
Number of Subjects and Description of Population
3.3.2
Subject Selection and Numbering
All subjects will be given a unique 5-digit subject identification number after signing the 
informed consent form (ICF).
3.4
Eligibility Criteria
3.4.1
Informed Consent
Informed consent will be freely obtained from all subjects (or their guardian or legally 
acceptable representative, as applicable for local laws). The ICF will be approved by the 
same Institutional Review Board (IRB) that approves this protocol. Additionally, the 
informed consent will cover the retrospective, screening, and prospective aspects of the 
trial.
Each ICF will comply with the International Council for Harmonisation (ICH) Good 
Clinical Practice (GCP) Guideline and local regulatory requirements. The investigator
will ensure that the sponsor reviews and authorizes any site-specific ICF used in the trial 
before submission to the IRB.
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The investigators may discuss trial availability and the possibility for entry with a 
potential subject without first obtaining consent. However, informed consent must be 
obtained and documented prior to initiation of any procedures that are performed solely 
for the purpose of determining eligibility for research, including withdrawal from current 
medication(s).
Potential subjects are free to refuse entry into the trial, or withdraw from the trial at any 
time, without justification, and there will be no consequences to their further care.
Prospective trial participants will be provided with controlled access to the electronic ICF 
(eICF) application by trial site staff. When the trial site staff and the participant agree that 
the participant has enough information to make an informed decision to participate, the 
participant will electronically sign in the eICF application and an electronic date and 
timestamp will be applied to the signature. The subject will be given a printed, signed 
copy of the ICF. Any other parties required by the IRB (trial site staff, witnesses, or 
legally authorized representative) are also required to sign electronically and these 
signatures will be stored with the eICF in accordance with the ICH GCP guideline and 
local regulatory requirements/guidelines. These signatures cannot be altered, removed, or 
copied.
Subjects may be asked to sign additional ICFs if the protocol is amended and the changes 
to the protocol result in additional information that needs to be provided to the subjects, 
so that they can make a knowledgeable and voluntary decision on trial participation.
Eligible participants include adult subjects with a current diagnosis of schizophrenia 
being treated with aripiprazole, or for whom aripiprazole treatment would be appropriate, 
as determined by the treating physician. Subjects must also meet all of the inclusion 
criteria (Section 3.4.2) and none of the exclusion criteria (Section 3.4.3).
3.4.2
Inclusion Criteria
Subjects are required to meet the inclusion criteria presented in Table 3.4.2-1.
Table 3.4.2-1
Inclusion Criteria
1.
Subject must be willing and able to give written (signed and dated) informed consent, which 
includes adherence to trial requirements and restrictions before enrolling in the trial. Subject must 
be willing to adhere to trial procedures, including troubleshooting of the Abilify MyCite app by a 
third party if needed.
2.
Subject must be able to read and understand English.
3.
Male and female subjects 18 to 65 years of age, inclusive, at the time of informed consent.
4.
Subjects are deemed appropriate, per investigator judgment, to use Abilify MyCite and to enter this 
interventional trial.
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Table 3.4.2-1
Inclusion Criteria
5.
Subject must possess a smartphone and is familiar with its use and is willing to download and 
interact with the Abilify MyCite app, completing all tasks as well as adequately operating all 
devices, as applicable. Caregiver/support person or other third party assistance can be utilized
throughout participation in the trial. However, subjects should be encouraged to complete all tasks 
themselves. At the conclusion of the study, the caregiver/support person will be asked (where 
applicable) to provide feedback via the Caregiver Involvement Scale. A subject with a smartphone 
that is not compatible with the Abilify MyCite app will be offered a loaner phone for the trial 
period.
6.
Subject possesses the capacity to utilize the technology interfaces (eg, open and navigate software 
applications using the touch screen) and telephone features of a smartphone (Android or iOS). The 
subject has satisfactory mobile phone reception (preferably 3 bars or more or have Wi-Fi) at home 
and/or at work for wireless carrier.
7.
Subject is cooperative, able to ingest oral medication, willing to complete all aspects of trial, and 
capable of reporting AEs.
8.
Clinical diagnosis of schizophrenia (defined by DSM-5) with a PANSS total score between 60-90.
9.
Subjects currently prescribed oral atypical antipsychotic medication including aripiprazole or 
appropriate for aripiprazole treatment for 6 months or longer.
10.
Subjects are required to have had an inpatient hospitalization for schizophrenia within the last 
48 months prior to entering the trial.
11.
Subject’s general medical condition such that participation in the trial does not pose any additional 
risk as per investigator’s judgment.
12.
Skin on the anterior chest just above the lower edge of the rib cage that is free of any 
dermatological problems (eg, dermatosis or dermatitis, open wounds, or other skin disorders such 
as warts, rashes, atopic dermatitis, or irritations).
3.4.3
Exclusion Criteria
Subjects will be excluded if they meet any of the exclusion criteria in Table 3.4.3-1.
Table 3.4.3-1
Exclusion Criteria
1.
Females who are breast-feeding and/or who are pregnant at the time of trial enrollment, or who 
plan to become pregnant during the trial.
2.
Sexually active males or WOCBP who do not agree to practice 2 different methods of birth control 
or remain abstinent during the trial and for 30 days after the last dose of Abilify MyCite. If 
employing birth control, 2 of the following precautions must be used: vasectomy, tubal ligation, 
vaginal diaphragm, intrauterine device, birth control pill, birth control implant, birth control depot 
injection, condom with spermicide, or sponge with spermicide.
3.
Any subject who participated in another clinical trial within 30 days of enrollment into the current 
trial.
4.
Subjects who are currently being treated with an LAI antipsychotic or have been treated with an 
LAI in the retrospective 6-month phase.
5.
Subjects with a current DSM-5 diagnosis other than schizophrenia, including schizoaffective 
disorder, bipolar I disorder, MDD, delirium, dementia, amnestic, or other cognitive disorders. Also, 
subjects with borderline, paranoid, histrionic, or antisocial personality disorder.
6.
Subject with any disorder including but not limited to intellectual developmental delay or disorder, 
major neurocognitive disorder or other condition that may impact the subject’s ability to participate 
in the trial or interact with the smartphone application.
7.
Subject who is likely to be incapable of using the Abilify MyCite technology, even with assistance.
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Table 3.4.3-1
Exclusion Criteria
8.
Subject who has 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 usability during the course of the 
trial, including but not limited to, hepatic, renal, respiratory, cardiovascular, endocrine, neurologic, 
hematologic, or immunologic disease as determined by the clinical judgment of the investigator.
9.
Subject with a known allergy to adhesive tape or any pertinent components of the patch or 
aripiprazole tablet embedded with an IEM sensor (Abilify MyCite).
10.
Any subject who, in the opinion of the investigator or the medical monitor, should not participate in 
the trial.
LAI = long-acting injectable; WOCBP = women of childbearing potential.
Nonchildbearing potential is defined as male and female subjects who are surgically 
sterile (ie, male subjects who have undergone bilateral orchidectomy and female subjects 
who have undergone bilateral oophorectomy and/or hysterectomy) and female subjects 
who have been postmenopausal for at least 12 consecutive months.
Subjects must agree to restrictions to medications as described in Section 4.
3.5
Endpoints
3.5.1
Primary Endpoint
The primary endpoint is the comparison of inpatient psychiatric hospitalization rates 
(proportion of subjects with ≥ 1 inpatient psychiatric hospitalization) between the 
retrospective period (Month 1 to 3) while subjects are on oral standard-of-care
antipsychotic treatment and the prospective period (Month 1 to 3) after the subjects
switch to Abilify MyCite.
3.5.2
Secondary Endpoint
Improved adherence based on overall PDC with Abilify MyCite versus retrospective oral 
atypical antipsychotics.
3.5.3
Exploratory Endpoints
 
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treatment. This will be followed, at investigator discretion, to either change to standard-
of-care antipsychotic treatment (eg, oral or LAI) or remain on Abilify MyCite for the 
second 3-month period (Months 4 to 6), during the prospective phase. The final trial visit 
will be on Month 6/ET and will be followed by a 30-day (± 3 day) safety follow-up 
period for subjects continuing on Abilify MyCite. For subjects completing Months 4 to 6 
on standard of care, a 30-day safety follow-up period is not required. Total length of 
participation in the trial will vary depending on the screening duration and if the subjects 
remain on Abilify MyCite treatment.
At the screening visit, informed consent will be obtained before any trial-related 
assessments or procedures are performed. Initiation of the Abilify MyCite treatment will 
commence at the baseline visit (Day 1) for the subjects who meet all applicable eligibility 
criteria (Section 3.4), based on a series of assessments conducted at the screening visit.
The first dose of Abilify MyCite is to be taken at the baseline (Day 1) visit (in the clinic) 
during onboarding, unless they have already taken their daily dose. Subjects should not 
take their oral standard-of-care medication that morning before the baseline visit.
During screening visit, the investigator will provide training on the correct use and 
required procedures associated with Abilify MyCite. The subject will be provided with 
patches, aripiprazole tablet embedded with an IEM sensor (Abilify MyCite) product, 
other supplies, and instructions on the procedures to be followed over the coming weeks.
Subjects will be monitored on the technology by the investigators, who can review the 
physician dashboard data and make changes to current treatment plan and therapy at their 
discretion. The investigators may request that a subject return to the site for unscheduled 
visits as deemed appropriate. In the event of an unscheduled visit, data collected will be 
at the investigator discretion per allowed data collection points noted in the schedule of 
assessments (Table 3.7-1). By Day 14 of the trial, if it is the opinion of the investigator 
that it is not appropriate for a subject to continue using Abilify MyCite, then the subject 
may be discontinued from trial participation but will be followed on oral atypical 
antipsychotic medication through the Month 6/ET visit.
Subjects will also visit the clinic for dispensing patches, Abilify MyCite product, and 
other supplies at Months 1, 2, 4, and 5. Any treatment changes, including reason for the 
change, will be recorded in the eCRF. Additionally, clinical evaluations will occur at 
Month 3 visit.
At the Month 6/ET visit, designated assessments and procedures will be conducted. The 
Month 6/ET visit marks the end of the assessment period. The subject will stop taking 
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Abilify MyCite product and will restart his/her standard-of-care treatment (routine 
follow-up from care teams). All trial materials will be returned to the trial site.
For subjects continuing on Abilify MyCite, a follow-up telephone contact will be made 
30 days (± 3 days) after the last dose of aripiprazole tablet embedded with an IEM sensor 
(Abilify MyCite) product (for subjects who withdraw early and for those who complete 
the trial). The Month 6/ET visit will serve as the final safety visit for subjects who 
complete the study on standard-of-care treatment.
Trial assessment time points are summarized in Table 3.7-1.
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Table 3.7-1
Schedule of Assessments
Prospective Phase (Day 1 to Month 6/ET)a
Follow
-Upb
Abilify MyCite treatment required
(Months 1 to 3)
Abilify MyCite or PRN 
oral atypical 
antipsychotic treatment
(Months 4 to 6)
Screening
Baseline
Month 
1
Month 
2
Month 
3
Month 
4
Month 
5
Month 
6/ET
Month 
7
Assessments
Days -45
to -1
Day 1
- 3/ + 2 days
- 3/ + 2 days
± 3 
days
Notes
Record retrospective hospitalization 
and intervention data per protocol
Xc
Informed consent
X
Section 3.4.1
Inclusion/exclusion criteria
X
Section 3.4
Demographic information
X
Psychiatric history
X
Urine pregnancy test (WOCBP)d
X
X
Section 3.7.3.2
Confirmation of diagnosis 
of schizophrenia by DSM-5
X
C-SSRS (Baseline/Screening Version)
X
Section 3.7.3.5
C-SSRS (Since Last Visit Version)
X
X
X
Section 3.7.3.5
ECG collection
X
Section 3.7.3.4
Vital signs
X
X
X
X
Section 3.7.3.3
Adverse events
X
X
X
X
X
Section 5
Discontinue prohibited medications
X
Section 4
Smartphone verification
X
Onsite onboarding with Abilify MyCite; 
subject pairs/applies patch
X
Section 3.2.2.2
Dispense aripiprazole tablet embedded with 
an IEM sensor (Abilify MyCite), patches, and 
other supplies
X
X
X
X
Xe
Xe
Review Abilify MyCite dashboard data every 
2 weeks
X
--Xf--
--Xf--
--Xf--
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a Monthly assessments will follow a 28-day schedule.
b A follow-up phone call for subjects who conclude the study on Abilify MyCite will occur 30 days (± 3 days) after the Month 6/ET visit.
c Retrospective hospitalization and intervention data will be collected only after trial eligibility is confirmed. This includes all psychiatric interventions (ie, 
hospitalizations, emergency department visits, partial hospitalization visits, intensive outpatient visits, assertive community treatment visits, outpatient 
visits for psychotherapy and/or medication management, etc.).
d Urine pregnancy tests may be repeated if the investigator suspects that a subject is pregnant.
e Abilify MyCite components (aripiprazole tablet embedded with an IEM sensor [Abilify MyCite], patches, and other supplies) will be dispensed and 
accountability performed only if subjects remain on Abilify MyCite treatment during Months 4 to 6 of the prospective phase. Any treatment changes, 
including reason for the change, will be recorded in the eCRF.
f The trial physician is expected to regularly review the Abilify MyCite dashboard data during active Abilify MyCite use as consistent with routine care, 
approximately every 2 weeks. Note that “--x--” indicates an activity that occurs multiple times during the period.
g Scales will be administered at the Month 6/ET visit for subjects who used Abilify MyCite during Months 4 to 6.
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3.7.1
Schedule of Assessments
3.7.1.1
Retrospective Phase (6 Months)
Subjects must have been prescribed oral antipsychotic standard-of-care pharmacotherapy
for at least 6 months or longer, with evidence of prescription (ie, pharmacy records), 
during the retrospective phase and prior to screening. Subjects administered 
antipsychotics other than aripiprazole may cross-titrate onto oral aripiprazole during the 
screening period at the discretion of the investigator to be eligible for trial participation.
All hospitalizations and all interventions (psychiatric only) will be recorded in the source 
documentation.
3.7.1.2
Screening Visit
Eligible subjects will come to the trial site, on a day agreed upon by the subject (and his 
or her caregiver/support person, if applicable) and the investigator, to undergo screening
assessments.
At the screening visit, the following will be performed:

Retrospective hospitalization and intervention data will be collected only after trial 
eligibility is confirmed.

Informed consent (Section 3.4.1).

The subject must provide documented informed consent before any other trial 
assessments or procedures are performed.

If the subject has a caregiver/support person, that caregiver/support person also 
must provide written informed consent.

Eligibility Assessment (Section 3.4).

All protocol inclusion and exclusion criteria will be reviewed by the investigator; 
only subjects who meet all of the inclusion criteria and none of exclusion criteria 
may be considered for further participation in the trial.

Obtain demographic information and psychiatric history.

Obtain urine sample for pregnancy test (women of childbearing potential [WOCBP]; 
Section 3.7.3.2).

Confirm diagnosis of schizophrenia by DSM-5.

Administer the suicidality assessment (C-SSRS baseline version;
Section 3.7.3.5).

Perform electrocardiogram (ECG) collection (Section 3.7.3.4).

Perform vital signs assessment (Section 3.7.3.3).

Monitor AEs, including device-related nonserious AEs (Section 5).

Discontinue prohibited medications (Section 4).
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
Smartphone verification: Each subject will be asked to confirm the availability of a 
suitable smartphone for the trial, in addition to confirming a wireless local area 
networking (wireless fidelity [Wi-Fi]) connectivity option is available to them. A 
subject with a smartphone that is not compatible with the Abilify MyCite app will be 
offered a loaner phone for the trial period.

 (Section 3.7.2.1.2).
3.7.1.3
Prospective Phase (6 Months)
The prospective phase is 6 months from the baseline visit (Day 1) to the Month 6/ET 
visit. Subjects will have their final assessment visit at Month 6/ET. Monthly assessments 
will follow a 28-day schedule.
In the event a scheduled assessment period visit is missed by a subject, the trial site will 
contact the subject immediately and reschedule another visit as close to the original visit 
schedule date as possible. After at least 2 phone calls are attempted, a certified letter will 
be sent to the subject. If a rescheduled visit falls outside of the allowable time window, 
then the investigator will contact the sponsor (or designee) to determine whether the 
subject can continue in the trial and to obtain approval to continue or discontinue the 
subject.
3.7.1.3.1
Baseline (Day 1)
After completion of the screening visit assessments and procedures, the subject will 
return for the baseline visit.
At the baseline visit, the following will be performed:

Obtain urine sample for pregnancy test (WOCBP; Section 3.7.3.2).

Administer the suicidality assessment (C-SSRS Since Last Visit Version; 
Section 3.7.3.5).

Perform vital signs assessment (Section 3.7.3.3).

Monitor AEs, including device-related nonserious AEs (Section 5).

Abilify MyCite system onboarding (Section 3.2.2.2).

The following will be dispensed to the subject:

Abilify MyCite products (aripiprazole tablet embedded with an IEM sensor), 
supplies, and patches (prescribed dose is recorded) sufficient for 1 month (from 
baseline [Day 1] to Month 1).

Instructions on how to install the Abilify MyCite smartphone application.

User Guide for Abilify MyCite including introductory video and reference guides.

Contact information for the call center.
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
The first dose of Abilify MyCite is to be taken at the baseline (Day 1) visit (in the 
clinic) during onboarding, unless they have already taken their daily dose. 
Subjects should not take their oral standard-of-care medication that morning 
before the baseline visit.

Review subject and investigator dashboards with the subject.






3.7.1.3.2
Months 1 and 2 Visits
At the Months 1 and 2 visits (- 3/ + 2 days), the following will be performed:

Abilify MyCite products (aripiprazole tablet embedded with an IEM sensor), 
supplies, and patches (prescribed dose is recorded) sufficient for 1 month will be 
dispensed. Any treatment changes, including reason for the change, will be recorded 
in the eCRF.

Accountability of patches and Abilify MyCite product (aripiprazole tablet embedded 
with an IEM sensor) supplies performed.

Review Abilify MyCite dashboard data every 2 weeks.

3.7.1.3.3
Month 3 Visit
Month 3 (- 3/ + 2 days) will be an investigator visit for the subject. At the Month 3 visit, 
the following will be performed:

Administer the suicidality assessment (C-SSRS Since Last Visit Version; 
Section 3.7.3.5).

Perform vital signs assessment (Section 3.7.3.3).

Monitor AEs, including device-related nonserious AEs (Section 5).

Abilify MyCite products (aripiprazole tablet embedded with an IEM sensor), 
supplies, and patches (prescribed dose is recorded) sufficient for 1 month will be 
dispensed. Any treatment changes, including reason for the change, will be recorded 
in the eCRF.

Accountability of patches and Abilify MyCite product (aripiprazole tablet embedded 
with an IEM sensor) supplies performed.
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
Review Abilify MyCite dashboard data every 2 weeks.




Healthcare utilization record evaluation (Section 3.7.1.4).




3.7.1.3.4
Months 4 and 5 Visits
At the Months 4 and 5 visits (- 3/ + 2 days), the following will be performed for subjects 
remaining on Abilify MyCite treatment:

Abilify MyCite products (aripiprazole tablet embedded with an IEM sensor), 
supplies, and patches (prescribed dose is recorded) sufficient for 1 month will be 
dispensed. Any treatment changes, including reason for the change, will be recorded 
in the eCRF.

Accountability of patches and Abilify MyCite product (aripiprazole tablet embedded 
with an IEM sensor) supplies performed.

Review Abilify MyCite dashboard data every 2 weeks.
3.7.1.3.5
Month 6/Early Termination Visit
Month 6/ET (- 3/ + 2 days) will be an investigator visit for the subject. In addition, 
Month 6/ET visit evaluations are to be completed for any subject withdrawn from the 
trial at any time (for any reason other than full withdrawal of the consent). At the 
Month 6/ET visit, the following will be performed:

Administer the suicidality assessment (C-SSRS Since Last Visit Version; 
Section 3.7.3.5).

Perform vital signs assessment (Section 3.7.3.3).

Monitor AEs, including device-related nonserious AEs (Section 5).

Accountability of patches and Abilify MyCite product (aripiprazole tablet embedded 
with an IEM sensor) supplies performed for subjects remaining on Abilify MyCite 
treatment. Any treatment changes, including reason for the change, will be recorded 
in the eCRF.

Review Abilify MyCite dashboard data every 2 weeks for subjects remaining on 
Abilify MyCite treatment.
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3.7.3
Safety Assessments
3.7.3.1
Adverse Events
Refer to Section 5, Reporting of AEs.
3.7.3.2
Clinical Laboratory Assessments
Urine pregnancy for WOCBP will be conducted at screening and Day 1. If deemed 
appropriate, serum pregnancy test will be performed if positive urine screen is detected. 
Additional clinical laboratory assessments will be performed at screening and at the 
investigator’s discretion to ensure safety of the subject but are not required as part of this 
trial.
3.7.3.3
Vital Signs
Vital signs will be performed at screening, baseline (Day 1), Month 3, Month 6/ET, and
at the investigator’s discretion at subsequent visits to ensure safety of the subject but are 
not required as part of this trial.
3.7.3.4
Electrocardiogram Assessments
Electrocardiograms will be collected by the subjects at screening to confirm eligibility. 
Electrocardiogram recordings will be obtained after the subject has been at rest for at
least 5 minutes. All ECGs will be reviewed by the investigator to assess normal from 
abnormal results. Any screening ECG with abnormal result(s) considered to be clinically 
significant can be repeated to confirm the finding(s) prior to excluding the subject.
3.7.3.5
Suicidality
Suicidality will be monitored throughout the trial using the C-SSRS.22 The C-SSRS was 
developed by a team of researchers at Columbia University to address the need for 
standardized classification of suicide reports to assess suicide risk. This scale consists of 
a baseline evaluation that assesses the lifetime experience of the subject with suicide 
events and suicidal ideation and a post-baseline evaluation that focuses on suicidality 
since the last assessment. The Baseline/Screening Version and the Since Last Visit 
version of the C-SSRS will be completed by trained trial site staff at the time points 
presented in the Schedule of Assessments Table 3.7-1.
3.7.4
End of Trial
The end of trial date is defined as the last date of contact or the date of final contact 
attempt from the post-treatment follow-up visit for the last subject completing or 
withdrawing from the trial.
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3.8
Stopping Rules, Withdrawal Criteria, and Procedures
3.8.1
Entire Trial
If the sponsor terminates or suspends the trial for any reason, prompt notification will be 
given to investigators, IRB, and regulatory authorities in accordance with regulatory 
requirements.
3.8.2
Individual Site
Individual trial site participation may be discontinued by the sponsor, the investigator, or 
the IRB if judged to be necessary for medical, safety, regulatory, ethical or other reasons 
consistent with applicable laws, regulations, and GCP. The investigator will notify the 
sponsor promptly if the trial is terminated by the investigator or the IRB at the site.
3.8.3
Individual Subject Discontinuation
3.8.3.1
Treatment Discontinuation
After enrollment, a subject may stop Abilify MyCite treatment permanently for a variety 
of reasons. Treatment discontinuations may be initiated by a subject who is not satisfied 
with treatment or may become medically necessary due to AEs, device-related nonserious 
AEs, required treatment with a disallowed medication or therapy, or other issues, as 
determined by the investigator. For subjects who elect to discontinue early for any 
reason, the sponsor would like to follow the subject for the total trial duration to track 
healthcare utilization with and without use of Abilify MyCite.
By Day 14 of the trial, if it is the opinion of the investigator that it is not appropriate for a 
subject to continue using Abilify MyCite, then the subject may be discontinued from trial 
participation but will be followed on oral atypical antipsychotic medication through the 
Month 6/ET visit.
If any subject discontinues the trial early, every effort should be made to complete the 
Month 6/ET evaluations (see Table 3.7-1) at that visit. All subjects (completers and early 
withdrawals) will be contacted to monitor for safety events via telephone or investigator
visit at 1 month (± 3 days) after the Month 6/ET visit.
3.8.3.2
Documenting Reasons for Treatment Discontinuation
A subject may discontinue Abilify MyCite for a number of reasons including those listed 
below:

Reasons related to AE:
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
Subject decides to discontinue because of annoyance or discomfort due to a 
nonserious AE which is not otherwise determined to be an undue hazard.

Continuing Abilify MyCite places the subject at undue risk as determined by the 
investigator (eg, a safety concern that is possibly, probably, or likely related to 
Abilify MyCite).

SAE.

Other potentially Abilify MyCite-related safety concerns or AEs.

Death.

Reasons unrelated to medical condition (provide detail and review AE history with 
subject).

Withdrawal of informed consent (complete written withdrawal of consent form).

Lost to follow-up.

Pregnancy (see Section 5.5).

Termination of all or part of the trial by the sponsor.
If the subject discontinues Abilify MyCite due to an AE, the investigator, or other trial 
personnel, will make every effort to follow the event until it has resolved or stabilized.
3.8.3.3
Withdrawal of Consent
All subjects have the right to withdraw their consent from further participation in the trial 
at any time without prejudice. Subjects cannot withdraw consent for use of data already 
collected as part of the trial, but only for future participation. The investigator can also 
discontinue a subject’s participation in the trial at any time if medically necessary. Unless 
the subject provides their written withdrawal of consent or there is other written 
documentation by the investigator confirming the subject’s verbal intent to completely 
withdraw from the trial, subjects should be followed for all protocol-specified evaluations 
and assessments, if possible.
Complete withdrawal of consent requires a subject’s refusal of all of the following 
methods of follow-up (these methods of follow-up will also be noted in the trial ICF):

Participation in all follow-up procedures specified in the protocol (whether in-clinic, 
by telephone, or by an in-home visit).

Participation in a subset of protocol-specified follow-up procedures (by a frequency 
schedule and method, as agreed by subject and staff).

Contact of the subject by trial personnel, even if only by telephone, to assess current 
medical condition, and obtain necessary medical or laboratory reports relevant to the 
trial’s objectives.
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
Contact of alternative person(s) who have been designated in source records as being 
available to discuss the subject’s medical condition, even if only by telephone, mail, 
or email (eg, family, spouse, partner, legal representative, friend, neighbor, or
physician).

Access to medical information from alternative sources (eg, hospital/clinic medical 
records, referring doctor’s notes, public records, dialysis, transplantation or vital 
registries, social media sources).
Withdrawal of consent is a critical trial event and therefore should be approached with 
the same degree of importance and care as is used in initially obtaining informed consent. 
The reasons for a subject’s intended withdrawal need to be completely understood, 
documented, and managed to protect the rights of the subject and the integrity of the trial. 
A subject may initially express their desire to discontinue Abilify MyCite administration, 
which is not equivalent to a complete withdrawal of consent for further participation (see 
Section 3.8.3.1). A subject may, however, indicate that further trial participation is 
creating a burden on their work or social schedule. Therefore, the investigator should 
follow the procedures outlined in Section 3.8.3.2 to determine if the subject can continue 
participation in the trial if modifications to his/her treatment and/or schedule of 
assessments can be accommodated. Only subjects who withdraw their permission for all 
of the above degrees of follow-up are considered to have completely withdrawn their 
consent to participate in the trial.
3.9
Screen Failures
A screen failure subject is one from whom informed consent is obtained and is 
documented in writing (ie, subject signs an ICF), but who is not started on trial treatment. 
For the purposes of this trial, Abilify MyCite treatment begins with the first 
administration of Abilify MyCite on Day 1 of the prospective phase. Subjects who sign 
an eICF but who are not started on treatment are permitted to be re-screened. In the event 
that the subject is re-screened for trial participation, and the re-screening is not completed 
within the original screening window, a new eICF must be signed.
3.10
Definition of Completed Subjects
The treatment period is defined as the time period during which subjects are evaluated for 
primary and/or secondary objectives of the trial irrespective of whether or not the subject 
actually received all doses of Abilify MyCite. For the purposes of this trial, subjects who 
complete the Month 6/ET visit will be defined as treatment completers. Subjects who are 
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evaluated at the last scheduled visit during the treatment period will be defined as trial 
completers.
3.11
Definition of Subjects Lost to Follow-up
Subjects who cannot be contacted on or before the last scheduled trial visit during the 
treatment period and who do not have a known reason for discontinuation (eg, withdrew 
consent or AE) will be classified as “lost to follow-up” as the reason for discontinuation.
The site will make 3 documented attempts to contact the subject by telephone and in the 
event the site is unable to reach the subject by telephone, the site will attempt to contact 
the subject via certified mail or an alternative similar method, where appropriate, before 
assigning a “lost to follow-up” status.
3.12
Subject Compliance
Subjects will be required to have at least 3 months of Abilify MyCite medication.
Noncompliant subjects will be followed throughout the trial period and analysis will be 
performed as described in Section 7.4. Discontinuation of noncompliant subjects is at the 
discretion of the investigator.
3.13
Protocol Deviations
In the event of a significant deviation from the protocol due to an emergency, accident, or 
mistake (eg, violation of informed consent process, Abilify MyCite dispensing or subject 
dosing error, treatment assignment error, subject enrolled in violation of eligibility 
criteria or concomitant medication criteria), the investigator or designee will contact the 
sponsor at the earliest possible time by telephone. The investigator and sponsor will come 
as quickly as possible to a joint decision regarding the subject’s continuation in the trial. 
This decision will be documented by the investigator and the sponsor and reviewed by 
the site monitor.
4
Restrictions
4.1
Prohibited Medications
The investigator may continue subjects on their stable/current mood stabilizer(s) or 
antidepressant dose (must be stable for at least 14-days prior to Abilify MyCite) to 
maintain clinical stability of the subjects during the trial. Other oral non-aripiprazole 
antipsychotic medications may be allowed if approved by the medical monitor and 
sponsor; however, clozapine will not be allowed. Nonoral formulations of these 
antipsychotic medications are also not allowed. The use of varenicline beyond the 
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screening visit is not allowed. If a subject is receiving varenicline at the screening visit, 
attempts should be made to discontinue the medication, if clinically feasible, to allow 
potential subjects to enter the trial.
Subjects must stop all other prohibited concomitant medications prior to administration 
of Abilify MyCite and for the duration of the trial.
Subjects must wash out from the following prohibited concomitant medications/therapies 
for the time periods specified:

Use of approved long-acting antipsychotics within 6 months prior to signing the ICF.
Inhibitors and inducers of cytochrome P450 (CYP)3A4 and inhibitors of CYP2D6 
isozymes are not allowed within 14 days (with the exception of fluoxetine which needs to 
be discontinued at least 28 days prior) prior to administration of Abilify MyCite and for 
the duration of the trial, since these are the pathways in which aripiprazole is 
metabolized.
An example list of CYP3A4 and CYP2D6 inhibitors and CYP3A4 inducers prohibited 
during the trial is provided in Table 4.1-1.
Table 4.1-1
Example List of CYP3A4 and CYP2D6 Inhibitors and 
CYP3A4 Inducers Prohibited During the Trial
CYP3A4 Inhibitors
Amiodarone
Fluvoxamine
Amprenavir
Indinavir
Aprepitant
Itraconazole
Chloramphenicol
Ketoconazole
Cimetidine
Nefazodone
Clarithromycin
Nelfinavir
Clotrimazole (if used orally)
Quinupristin/Dalfopristin 
Delavirdine
Ritonavir
Diltiazem
Saquinavir
Erythromycin
Troleandomycin
Fluconazole
Verapamil
CYP2D6 Inhibitors
Celecoxib
Hydroxyzine
Chloroquine
Methadone
Chlorpheniramine
Moclobemide
Clemastine
Paroxetine
Clomipramine
Pyrilamine
Diphenhydramine
Quinidine
Fluoxetine
Terbinafine
Halofantrine
Tripelennamine
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Table 4.1-1
Example List of CYP3A4 and CYP2D6 Inhibitors and 
CYP3A4 Inducers Prohibited During the Trial
CYP3A4 Inducers
Carbamazepine
Phenytoin
Dexamethasone
Primidone
Efavirenz
Rifampin
Nevirapine
St. John's wort
Phenobarbital
Troglitazone
Note: The above is not an exhaustive list and there may be additional CYP3A4 and CYP2D6 inhibitors 
and CYP3A4 inducers that are prohibited during the trial.
4.2
Restricted Medications
Use and washout of any other therapy (prescription medication, over-the-counter, herbal 
medication, or vitamins) not listed in Section 4.1 must be approved by the sponsor and 
the medical monitor.
Benzodiazepine use is allowed up to a maximum of 6 mg/day lorazepam or equivalent, 
but not within 8 hours of any rating scales during the trial. The use of intramuscular
lorazepam is also permitted for emergent agitation, but only if deemed absolutely 
necessary by the investigator. The following guide should be used to determine 
approximate lorazepam equivalents: 1 mg lorazepam; = 5 mg diazepam; = 15 mg 
oxazepam; = 15 mg clorazepate. Subjects must not be on more than one benzodiazepine 
beyond the screening visit.
If a subject is receiving 2 benzodiazepines at the screening visit (eg, lorazepam and 
oxazepam), attempts should be made to discontinue one of the benzodiazepines, if 
clinically warranted, to allow potential subjects to enter the trial. The second 
benzodiazepine should be tapered off over an appropriate amount of time within the 
45-day screening period to prevent side effects, and the subject should be maintained on 
the remaining benzodiazepine for at least 14 days prior to the administration of Abilify 
MyCite. Benzodiazepine use is allowed during the trial to manage AEs such as agitation, 
anxiety, and insomnia; however, non-benzodiazepine sleep aids are recommended for 
insomnia. Combined use of both drug classes (ie, benzodiazepines and non-
benzodiazepine sleep aids) as treatment for insomnia is not allowed. Benzodiazepine use 
should be discontinued as soon as the AE for which it was initiated subsides, as per the 
investigator’s discretion to avoid any withdrawal effects.
Medications that are restricted during the trial are listed in Table 4.2-1.
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Table 4.2-1
Medications Restricted During the Trial
Medication
Screening
Treatment Period
Anticholinergicsa
4 mg/day benztropine or 
equivalent
4 mg/day benztropine or equivalent
Propranolol (for akathisia 
or tremor)b, c
Maximum 60 mg propranolol per 
day
Maximum 60 mg propranolol per day
Benzodiazepinesb
-
No more than one benzodiazepine and 
not in combination with other sleep 
aid medication
aAnticholinergics are not allowed within 12 hours of any rating scales during any phase of the trial.
bIs not allowed within 8 hours of any rating scales during any phase of the trial.
cSubjects receiving propranolol for heart disease may remain on stable, pretrial doses, as needed, 
throughout the trial, so long as the total dose does not exceed 60 mg/day.
5
Reporting of Adverse Events
The following describes the methods and timing for assessing, recording, and analyzing 
safety parameters, as well as the procedures for eliciting reports of and recording and 
reporting AEs and intercurrent illnesses and the type and duration of the follow-up of 
subjects after AEs.
5.1
Definitions
An AE is defined as any untoward medical occurrence in a subject or clinical trial subject 
administered a medicinal product and which does not necessarily have a causal 
relationship with this treatment. Adverse events would not include information recorded 
as psychiatric history at screening for pre-planned procedures for which the underlying 
condition was known and no worsening occurred. An adverse reaction is any untoward 
and unintended response to Abilify MyCite related to any dose administered.
A suspected adverse reaction is any AE for which there is a reasonable possibility that 
Abilify MyCite caused the AE. For the purpose of Investigational New Drug (IND) 
safety reporting, “reasonable possibility” means there is evidence to suggest a causal 
relationship between Abilify MyCite and the AE. Suspected adverse reaction implies a 
lesser degree of certainty about causality.
An SAE includes any event that results in any of the following outcomes:

Death.

Life-threatening; ie, the subject was, in the opinion of the investigator, at 
immediate risk of death from the event as it occurred. It does not include an event 
that, had it occurred in a more severe form, might have caused death.
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
Persistent or significant incapacity/disability or substantial disruption of the 
ability to conduct normal life functions.

Requires inpatient hospitalization or prolongs hospitalization.

Hospitalization itself should not be reported as an SAE; whenever possible the 
reason for the hospitalization should be reported.

Hospitalizations or prolonged hospitalizations for social admissions (ie, those 
required for reasons of convenience or other non-medical need) are not 
considered SAEs.

Congenital anomaly/birth defect.

Other medically significant events that, based upon appropriate medical 
judgment, may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed above; eg, allergic 
bronchospasm requiring intensive treatment in an emergency room or home, 
blood dyscrasias or convulsions that do not result in hospitalization, or the 
development of drug dependency or drug abuse.
A device-related SAE includes any event that results in any of the following outcomes:

An event that reasonably suggests that a device has or may have caused or 
contributed to a death or serious injury.

Contributed to is defined as a death or serious injury that was or may have 
been attributed to a medical device, or that a medical device was or may have 
been a factor in a death or serious injury, including events occurring as a 
result of any of the following:

Failure.

Malfunction.

Improper or inadequate design.

Manufacture.

Labeling.

User error.

Serious injury means an injury or illness that includes any of the following:

Is life-threatening.

Results in permanent impairment of a body function or permanent damage to 
a body structure.

Necessitates medical or surgical intervention to preclude permanent 
impairment of a body function or permanent damage to a body structure. 
Permanent means irreversible impairment or damage to a body structure or 
function, excluding trivial impairment or damage.

Any of the following events that manufacturers or importers become aware of that 
reasonably suggests that one of their marketed devices:
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
May have caused or contributed to a death or serious injury.

Has malfunctioned and that the device or a similar device marketed by the 
manufacturer or importer would be likely to cause or contribute to a death or 
serious injury if the malfunction were to recur.
For the purpose of this trial, device-related SAEs include any event that is related to the 
IEM, patch, or the phone and app (reported to Otsuka).
If an AE is related to the patch, then the skin irritation scoring system will be completed 
by the investigator. Patch-related AEs Grade 2 or above will be considered medically 
significant for purposes of this trial.
Nonserious AEs are all AEs that do not meet the criteria for a "serious" AE.
Device-related nonserious AEs are considered skin reactions caused by patch graded 
lower than Grade 2.
Immediately Reportable Event (IRE):

Any SAE.

Any AE related to occupational exposure.

Any nonserious AE related to the Abilify MyCite Patch.

Potential serious hepatotoxicity (see Section 5.4). 

Pregnancies are also defined as IREs. Although normal pregnancy is not an AE, it 
will mandate Abilify MyCite discontinuation and must be reported on an IRE 
form to the sponsor. Pregnancy will only be documented on the AE eCRF if there 
is an abnormality or complication.
Severity: AEs will be graded on a 3-point scale and reported as indicated on the eCRF. 
The intensity of an adverse experience is defined as follows:
1 = Mild:
Discomfort noticed, but no disruption to daily activity.
2 = Moderate:
Discomfort sufficient to reduce or affect normal daily activity.
3 = Severe:
Inability to work or perform normal daily activity.
Causality: Assessment of causal relationship of an AE to the use of Abilify MyCite is 
defined as follows:
Related: 
There is a reasonable possibility of a temporal and causal 
relationship between Abilify MyCite and the AE.
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Not Related: 
There is no temporal or causal relationship between Abilify 
MyCite and the AE.
5.2
Eliciting and Reporting Adverse Events
The investigator will periodically assess subjects for the occurrence of AEs from the time 
the eICF is signed until the end of the trial. For this trial, information on AEs will be 
followed for up to 7 months (including the safety follow-up period) after the first dose of 
Abilify MyCite has been administered. To avoid bias in eliciting AEs, subjects should be 
asked the non-leading question: “How have you felt since your last visit?” All AEs 
(serious and nonserious) reported by the subject must be recorded on the source 
documents and eCRFs provided by the sponsor. Serious AE collection is to begin after a 
subject has signed the eICF.
Use medical terminology in AE reporting. Adverse events should be reported as a single 
unifying diagnosis whenever possible or, in the absence of a unifying diagnosis, as 
individual signs or symptoms. Exacerbation or disease progression should be reported as 
an AE only if there are unusual or severe clinical features that were not present, or 
experienced earlier, or not expected based on the course of the condition.
In addition, the sponsor must be notified immediately by telephone, fax, or email of any 
IREs according to the procedure outlined below, in Section 5.3. Special attention should 
be paid to recording hospitalization and concomitant medications.
5.3
Immediately Reportable Events
The investigator must immediately report after either the investigator or site personnel 
become aware of any SAE, potential serious hepatotoxicity, or confirmed pregnancy, by 
telephone, fax, or email to the sponsor using the contact information on the cover page of 
this protocol. An IRE form must be completed and sent by email, fax, or overnight 
courier to the sponsor (please note that the IRE form is NOT the AE eCRF).
Subjects experiencing SAEs should be followed clinically until their health has returned 
to baseline status, or until all parameters have returned to normal or have otherwise been 
explained. It is expected that the investigator will provide or arrange appropriate 
supportive care for the subject and will provide prompt updates on the subject’s status to 
the sponsor.
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5.4
Potential Serious Hepatotoxicity
For a subject who experiences an elevation in aspartate aminotransferase (AST) or 
alanine aminotransferase (ALT) that is ≥ 3 times the upper limit of normal (ULN), a total 
bilirubin level should also be evaluated. If the total bilirubin is ≥ 2 times the ULN, 
complete an IRE form with all values listed and also report as an AE on the eCRF.
5.5
Pregnancy
Women of childbearing potential are defined as female subjects for whom menstruation 
has started and who are not documented as sterile (ie, have had a bilateral oophorectomy 
and/or hysterectomy or who have been postmenopausal for at least 12 months).
For WOCBP and for men who are sexually active, there must be a documented 
agreement that the subject and/or their partner will take effective measures (ie, double 
barrier method) to prevent pregnancy during the course of the trial and for 30 days after 
the last dose of Abilify MyCite. Unless the subject is sterile (ie, women who have had a 
bilateral oophorectomy and/or hysterectomy or who have been postmenopausal for at 
least 12 consecutive months; or men who have had a bilateral orchidectomy) or remains 
abstinent, 2 of the following precautions must be used: vasectomy, tubal ligation, vaginal 
diaphragm, intrauterine device, birth control pills, birth control depot injection, birth 
control implant, condom with spermicide, or sponge with spermicide. Any single method 
of birth control, including vasectomy and tubal ligation, may fail, leading to pregnancy. 
The contraceptive method will be documented at each trial visit.
Before enrolling WOCBP in this clinical trial, investigators must review the below 
guidelines about trial participation with all WOCBP. The topics should generally include:

General information.

ICF.

Pregnancy prevention information.

Drug interactions with hormonal contraceptives.

Contraceptives in current use.

Guidelines for the follow-up of a reported pregnancy.
Before trial enrollment, WOCBP must be advised of the importance of avoiding 
pregnancy during trial participation and the potential risk factors for an unintentional 
pregnancy. The subject must sign an ICF stating that the above-mentioned risk factors 
and the consequences were discussed with her.
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A urine and/or serum pregnancy test for human chorionic gonadotropin will be performed 
at screening and Day 1 on all WOCBP. If a urine test is performed and is positive, the 
investigator will follow-up with a confirmatory serum test.
During the trial, all WOCBP should be instructed to contact the investigator immediately 
if they suspect they might be pregnant (eg, missed or late menstrual cycle).
If a subject is suspected to be pregnant before she receives Abilify MyCite, the Abilify 
MyCite administration must be withheld until the results of serum pregnancy tests are 
available. If the pregnancy is confirmed, the subject must not receive Abilify MyCite and 
must not be enrolled in the trial. If pregnancy is suspected while the subject is taking 
Abilify MyCite, it must be withheld immediately (if reasonable, taking into consideration 
any potential withdrawal risks) until the result of the pregnancy test is known. If 
pregnancy is confirmed, Abilify MyCite will be permanently discontinued in an 
appropriate manner (eg, dose tapering if necessary for subject safety) and the subject will 
be withdrawn from the trial. [Exceptions to trial discontinuation may be considered for 
life-threatening conditions only after consultations with the Clinical Safety and 
Pharmacovigilance department (see the cover page of this protocol for contact 
information).]
The investigator must immediately notify the sponsor of any pregnancy associated with 
Abilify MyCite exposure during the trial and for 30 days after the last dose of Abilify 
MyCite and record the event on the IRE form and forward it to the sponsor. The sponsor 
will forward Pregnancy Surveillance Form(s) for monitoring the outcome of the 
pregnancy. 
Protocol-required procedures for trial discontinuation and follow-up must be performed 
on the subject unless contraindicated by pregnancy (eg, x-ray studies). Other appropriate 
pregnancy follow-up procedures should be considered, if indicated. In addition, the 
investigator must report to the sponsor, on appropriate Pregnancy Surveillance Form(s), 
follow-up information regarding the course of the pregnancy, including perinatal and 
neonatal outcome. Infants will be followed for a minimum of 6 months from the date of 
birth.
5.6
Procedure for Breaking the Blind
Not applicable, this is an open-label trial.
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5.7
Follow-up of Adverse Events
5.7.1
Follow-up of Nonserious Adverse Events
Nonserious AEs that are identified at any time during the trial must be recorded on the 
AE eCRF with the current status (ongoing or resolved/recovered) noted. All nonserious 
events (that are not IREs) that are ongoing at the last scheduled contact will be recorded 
as ongoing on the eCRF. For any AE having been identified throughout the trial, during 
analysis, additional relevant psychiatric history information may be requested by the 
sponsor to further ascertain causality (including, but not limited to, information such as 
risk related behavior, family history, and occupation).
5.7.2
Follow-up of Serious Adverse Events and Immediately 
Reportable Events
This trial requires that subjects be actively monitored for SAEs and IREs up to 1 month 
after the last dose of Abilify MyCite is administered.
Serious AEs and nonserious IREs that are identified or ongoing at the last scheduled 
contact must be recorded as such on the AE eCRF page. If updated information (eg, 
resolved status) on SAE or IRE status becomes available after a subject’s last scheduled 
contact (up to the last in-clinic visit for the entire trial), this must be reported to the 
sponsor and recorded on the AE eCRF page, according to the appropriate reporting 
procedures. The investigator will follow SAEs until the events are resolved, stabilized, or 
the subject is lost to follow-up or has died. Resolution means that the subject has returned 
to the baseline state of health and stabilized means that the investigator does not expect 
any further improvement or worsening of the subject’s condition. The investigator will 
continue to report any significant follow-up information to the sponsor up to the point the 
event has resolved or stabilized, or the subject is lost to follow-up or has died.
5.7.3
Follow-up and Reporting of Serious Adverse Events and 
Immediately Reportable Events Occurring after Last Scheduled 
Contact
Any new SAEs or IREs reported to the investigator, which occur after the last scheduled 
contact and are determined by the investigator to be reasonably associated with the use of 
Abilify MyCite, should be reported to the sponsor. This may include SAEs or IREs that 
are captured on follow-up telephone contact or at any other time point after the defined 
trial period. The investigator should follow SAEs or IREs identified after the defined trial 
period and continue to report any significant follow-up information to the sponsor until 
the events are resolved or stabilized, or the subject is lost to follow-up or has died.
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6
Pharmacokinetic Analysis
Not applicable, no pharmacokinetic assessments will be performed in this trial.
7
Statistical Analysis
7.1
Sample Size
The primary endpoint of this trial compares the paired proportions of inpatient psychiatric 
hospitalization during the retrospective period (Month 1 to 3) and the prospective period 
(Month 1 to 3), which will be analyzed using a McNemar test.
Based on published results of other similar studies for the particular time periods 
(retrospective Month 1 to 3 and prospective Month 1 to 3)23,24 we are evaluating, it is 
reasonable to assume that 15.5% of subjects are hospitalized during retrospective 
Month 1 to 3 and 7% are hospitalized during prospective Month 1 to 3; about 5% of 
subjects who are not hospitalized retrospective will be hospitalized prospective, while 
13.5% of subjects who are hospitalized retrospective will not be hospitalized. With this 
assumption, 200 completed subjects will provide 80% power (alpha = 0.05 two-sided) to 
detect a difference of 8.5% in 2 paired hospitalization proportions between pre-switch 
and post-switch periods while the proportion of total discordant pairs is 18.5%. In 
addition, this sample size will provide 80% power for the comparison of retrospective 
Month 4 to 6 vs prospective Month 4 to 6, assuming 30% of the subjects are hospitalized 
pre-switch (12.5% subjects will be hospitalized post-switch and another 17.5% won’t 
have hospitalization post-switch) and, overall, 20% are hospitalized post-switch (among 
them, 12.5% subjects are hospitalized both pre-switch and post-switch and 7.5% have no 
hospitalization pre-switch).
Two interim analyses are planned at when 50% and 70% of subjects have completed the 
prospective period (Month 1 to 3); in order to conserve the overall Type I error at 0.05 
level, 224 to 300 evaluable subjects are needed to complete the 3-month treatment to 
maintain 80% power. This sample size assumes the 3 sequential tests are made using 
LanDeMets Spending Function25 with O’Brien-Fleming boundary, a futility conditional 
power of 15% is built in the sample size calculation to allow the trial to stop for futility. 
Based on the conditional power and the alpha level at the interim analysis, the trial could 
stop for efficacy or futility, continue with initially planned 224 sample size or increase to 
up to 300 if the conditional power fall between 30% to 80% (Section 7.4.4). The 2-sided 
alpha levels for these 2 interim analyses are 0.00312 and 0.0139 respectively, and the 
alpha left for the final analysis will be 0.04528.
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7.2
Datasets for Analysis
The safety dataset includes all subjects that were administered at least one dose of Abilify 
MyCite.
The following analysis samples are defined for this trial:

Enrolled Sample: comprises all subjects who sign an eICF for the trial.

Prospective Safety Sample: comprises all subjects who receive at least one dose of
Abilify MyCite in the prospective phase.

Efficacy Sample: the core dataset for all efficacy analyses is the modified Intent-to-
Treat (mITT) dataset which will consist of data from all subjects entering the 
prospective phase who have completed the first 3-months of dosing on Abilify 
MyCite. However, as will be described below, in order to handle missing data and 
restrictions imposed by different types of analyses (eg, change from baseline 
analysis), other datasets derived from the ITT dataset will be used for the efficacy 
analyses.
7.3
Handling of Missing Data
For the primary variable, the analysis will be based on the proportion of days with good 
patch coverage during the trial and no imputation will be performed for missing data. For 
analysis of change from baseline (Day 1), last-observation-carried-forward (LOCF) and 
observed-cases (OC) methods will be used, as considered applicable. No imputation will 
be performed for other missing data, unless specified otherwise.
7.4
Primary and Secondary Endpoint Analyses
7.4.1
Primary Endpoint Analysis
The primary endpoint of this trial is the comparison of inpatient psychiatric 
hospitalization rates (proportion of subjects with ≥ 1 inpatient psychiatric 
hospitalization[s]) between the retrospective period (Months 1 to 3) while on oral 
standard-of-care antipsychotic treatment and the prospective period (Months 1 to 3) after 
the switch to Abilify MyCite. This will be achieved by testing for statistically significant 
(at 2-sided overall alpha = 0.05). The analysis will be performed using a McNemar test 
on those who have hospitalization data during Months 1 to 3 prior to the screening period 
and during Months 1 to 3 after switch to Abilify MyCite.
7.4.2
Secondary Endpoint Analysis
The secondary endpoint is:
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7.4.4
Interim Analysis
Two interim analysis are planned when 50% and 70% of subjects have completed the 
prospective phase (3 months). At the end of the interim analysis, a decision will be made 
to continue with/without sample size increase, stop for efficacy or stop for fertility based 
on the p-value and conditional power from the interim data (as described in 
Table 7.4.4-1). Subjects will continue to be enrolled into the trial during the interim 
analysis; if the trial is stopped due to futility, all randomized subjects will be terminated; 
however, if the interim analysis stops the trial for efficacy, then all randomized subjects 
will continue until the last observation. Subjects in screening will be discontinued and no 
further randomization will occur. The 2-sided alpha levels for these 2 interim analyses are 
0.00312 and 0.0139 respectively, and the alpha left for the final analysis will be 0.04528. 
The sample size will be re-estimated only based on the conditional power determined at 
the interim analysis. The adaptive designs methodology published by Chen, Dements and 
Lan (2004)26 will be used to increase the sample size based on the estimate of the 
treatment effect size of the primary efficacy endpoint at interim, possibly combined with 
other external information, without inflating the Type I error. Should the timing or 
frequency of the interim analysis be different from the previously specified, stopping 
boundary would be re-calculated using the alpha spending function.
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The Interim Analysis Plan and the statistical analysis plan will be developed to document 
the details of data flow, statistical methods and other logistical considerations relating to 
the interim analyses. Based on the interim analysis results, the trial sample size will be 
adjusted according to Table 7.4.4-1.
Table 7.4.4-1
Sample Size Re-estimation Schemes
Interim Results
Interim Analysis 
Recommendation
Sample Size (completers)
P – value less than specified 
alpha level at interim
Stop for efficacy
About 100 or 157
Conditional power ≥ 80%
No adaption to the planned 
sample size
224
Conditional power ≥30% and 
< 80%
Increase sample size up to 300
300
Conditional power ≥15% and 
< 30%
No adaption to the planned 
sample size
224
Conditional power < 15%
Stop the trial for futility
About 100 or 157
7.5
Analysis of Demographic and Baseline Characteristics
Baseline demographic characteristics including age, race, ethnicity, gender, weight, 
height and body mass index will be summarized by descriptive statistics (frequency, 
mean, median, SD, maximum, minimum, and percentage when applicable).
Baseline disease severity and psychiatric history will be also be summarized by 
descriptive statistics.
7.6
Safety Analysis
In general, baseline measurements of safety variables are defined as the last 
measurements prior to the first dosing of Abilify MyCite for the prospective phase of the 
trial. All safety summaries will be descriptive in nature.
7.6.1
Adverse Events
All AEs will be coded by system organ class and Medical Dictionary for Regulatory 
Activities (MedDRA) preferred term. The incidence of the following events will be 
summarized:

Treatment-emergent AEs (TEAEs).

TEAEs by severity.

TEAEs potentially causally related to Abilify MyCite.

Device-related TEAEs.

TEAEs with an outcome of death.
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
Serious TEAEs.

TEAEs leading to discontinuation of Abilify MyCite.
7.6.2
Clinical Laboratory Data
The urine pregnancy test and confirmatory serum test (if applicable) at screening on all 
WOCBP will be provided in a listing.
7.6.3
Vital Signs Data
Vital sign data (observed and change from baseline data) and the incidence of potentially 
clinically relevant vital signs will be summarized. Vital sign data will be presented in a 
listing.
7.6.4
Electrocardiogram Data
Electrocardiogram data will be presented in a listing.
7.6.5
Suicidality Assessment
The suicidality assessment data will be analyzed for evidence of any treatment-emergent 
issues related to suicidal ideation or behavior.
8
Management of Investigational Medicinal Product
8.1
Packaging and Labeling
Abilify MyCite will be provided to the investigators and the persons designated by the 
investigator(s) or institution(s) by the sponsor or designated agent. The aripiprazole tablet 
embedded with an IEM sensor (Abilify MyCite) products will be supplied in bottles. 
Each bottle used in the dosing period will be labeled to clearly disclose the subject 
identification (ID), compound ID, trial number, sponsor’s name and address, instructions 
for use, route of administration, appropriate precautionary statements, and other 
information as required by local regulatory authorities.
8.2
Storage
The aripiprazole tablet embedded with an IEM sensor (Abilify MyCite) products and 
patches will be stored in a securely locked cabinet or enclosure. Access will be limited to 
investigators and their designees. Neither investigators nor any designees may provide 
medical device to any subject not participating in this protocol.
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The medical device should be stored with, and in the same conditions as, the aripiprazole 
tablets embedded with an IEM sensor. The investigator or designee will maintain a 
temperature log in the storage area recording the temperature at least once each working 
day.
8.3
Accountability
The investigator or designee must maintain an inventory record of Abilify MyCite 
(patches and aripiprazole tablet embedded with an IEM sensor) received, dispensed, 
administered, and returned. Any treatment changes, including reason for the change, will 
be recorded in the eCRF.
8.4
Returns and Destruction
Upon completion or termination of the trial, all unused and/or partially used aripiprazole 
tablets embedded with an IEM sensor (Abilify MyCite) products and patches must be 
destroyed at the trial site(s). The assigned investigator or designee will facilitate the 
destruction of unused and/or partially used aripiprazole tablets embedded with an IEM 
sensor (Abilify MyCite) products and patches.
8.5
Reporting of Product Quality Complaints
A Product Quality Complaint (PQC) is any written, electronic, or verbal communication 
by a healthcare professional, consumer, subject, medical representative, Competent 
Authority, regulatory agency, partner, affiliate or other third party that alleges 
deficiencies or dissatisfaction related to identity, quality, labeling, packaging, reliability, 
safety, durability, tampering, counterfeiting, theft, effectiveness or performance of a drug 
product or medical device after it is released for distribution. Examples include, but are 
not limited to, communications involving:

Failure/malfunction of a product to meet any of its specifications.

Incorrect or missing labeling.

Packaging issues (eg, damaged, dirty, crushed, missing product).

Bottle defects (eg, under/over-fill, no safety seal).

Vial defects.

Product defect (eg, odor, chipped, broken, embossing illegible).

Loss or theft of product.
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8.5.1
Eliciting and Reporting Product Quality Complaints
The investigator or designee must record all PQCs identified through any means from the 
receipt of Abilify MyCite from the sponsor, or sponsor’s designee, through and including 
reconciliation and up to destruction, including subject dosing. The investigator or 
designee must notify the sponsor (or sponsor’s designee) by telephone within 24 hours of 
becoming aware of the PQC according to the procedure outlined below.

Phone - Abilify MyCite dedicated team at 
.
Identification of a PQC by the subject should be reported to the site investigator, who 
should then follow one of the reporting mechanisms above.
8.5.2
Information Required for Reporting Purposes

Description of complaint.

Reporter identification (eg, subject, investigator, site, etc.).

Reporter contact information (eg, address, phone number, email address).

ID of material (product/compound name, coding).

Clinical protocol reference (number and/or trial name).

Dosage form/strength (if known).

Pictures (if available).

Availability for return.
8.5.3
Return Process
Indicate during the report of the PQC if the complaint sample is available for return. If 
complaint sample is available for return, return it in the product retrieval package, which 
will be provided by the sponsor.
It must be documented in the site accountability record that a complaint sample for a 
dispensed kit has been forwarded to the sponsor for complaint investigation.
8.5.4
Assessment/Evaluation
Assessment and evaluation of PQCs will be handled by the sponsor.
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9
Records Management
9.1
Source Documents
Source documents are defined as the results of original observations and activities of a 
clinical investigation. Source documents will include but are not limited to progress 
notes, electronic data, screening logs, and recorded data from automated instruments. All 
source documents pertaining to this trial will be maintained by the investigators and made 
available for direct inspection by authorized persons.
Investigator(s)/institution(s) will permit trial-related monitoring, audits, IRB review, and 
regulatory inspection(s) by providing direct access to source data/documents by 
authorized persons as defined in the ICF. In all cases, subject confidentiality must be 
maintained in accordance with local regulatory requirements.
9.2
Data Collection
During each subject’s visit to the clinic, a clinician participating in the trial will record 
progress notes to document all significant observations. At a minimum, these notes will 
contain:

Documentation of the informed consent process, including any revised consents.

Documentation of the investigator’s decision to enroll the subject into the trial, the 
review of all inclusion/exclusion criteria prior to Abilify MyCite administration, and 
confirmation of the subject’s actual participation in the trial.

The date of the visit and the corresponding visit or day in the trial schedule.

General subject status remarks, including any significant medical findings. The 
severity, frequency, duration, action taken, and outcome of any AEs and the 
investigator's assessment of relationship to Abilify MyCite must also be recorded.

Any changes in concomitant medications or dosages.

A general reference to the procedures completed.

The signature (or initials) and date of all clinicians who made an entry in the progress 
notes.
In addition, any contact with the subject via telephone or other means that provides 
significant clinical information will also be documented in the progress notes as 
described above.
Source documents and source data will be captured electronically in this trial and will 
meet the same fundamental elements of data quality (eg, attributable, legible, 
contemporaneous, original, and accurate) as paper records. These data will be collected 
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into a system that is fully validated. Changes to the data will be captured by an automatic 
audit trail.
The trial site will be given a tablet to directly record subject data and clinical 
observations on electronic forms. Designated trial site staff will not be given access to the 
system until they have been appropriately trained. Information to be originally captured 
and reviewed electronically shall include details of the subject visit and the 
protocol-required assessments performed as a part of these visits, psychiatric history, 
AEs, and concomitant medications. Because this trial is using an electronic source record 
as the original point of data capture, there is no additional data entry step for the trial site 
for data collected directly into the application – rather, the electronic source record 
directly populates the trial database.
Some data may be captured via paper and then entered into the eSource system. These 
and any other data treated in this manner will be source data verified by the trial clinical 
research associate, and the location of the source data (ie, eSource, paper, or a local 
electronic system) will be documented before the trial start. Any changes to information 
in paper source documents will be initialed and dated on the day the change is made by a 
trial site staff member authorized to make the change. Changes will be made by striking a 
single line through erroneous data (so as not to obliterate the original data), and clearly 
entering the correct data (eg, wrong data right data). If the reason for the change is not 
apparent, a brief explanation for the change will be written in the source documentation 
by the clinician.
Another exception will be safety laboratory, where the official source documentation will 
be considered the report issued by the analyzing laboratory.
Remote monitoring of the original electronic source records will take place; however, 
on-site monitoring inspections will continue to take place in order to review data entry of 
source documentation directly captured on paper and transcribed into the system, to 
ensure protocol adherence, to assess trial site operational capabilities, and to perform 
other monitoring activities that cannot be performed remotely.
At the end of the trial, the investigator must certify that the data entered into the eSource 
application are complete and accurate. After database lock, the investigator will receive 
an electronic copy of the subject data.
9.3
File Management at the Trial Site
The investigator will ensure that the trial site file is maintained in accordance with 
Section 8 of the ICH GCP Guideline E6 and as required by applicable local regulations. 
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The investigator/institution will take measures to prevent accidental or premature 
destruction of these documents.
9.4
Records Retention at the Trial Site
Food and Drug Administration regulations require all investigators participating in 
clinical drug trials to maintain detailed clinical data for one of the following periods:

A period of at least 2 years after the date on which a New Drug Application is 
approved by the FDA.

A period of 2 years after the sponsor has notified the FDA that investigation with this 
drug is discontinued.
The investigator must not dispose of any records relevant to this trial without either 
(1) written permission from the sponsor or (2) provision of an opportunity for sponsor to 
collect such records. The investigator will be responsible to maintain adequate and 
accurate electronic or hard copy source documents of all observations and data generated 
during this trial including any data clarification forms received from the sponsor. Such 
documentation is subject to inspection by the sponsor and relevant regulatory authorities. 
If the investigator withdraws from the trial (eg, due to relocation or retirement), all 
trial-related records should be transferred to a mutually agreed-upon designee within a 
sponsor-specified timeframe. Notice of such transfer will be given to the sponsor in 
writing.
10
Quality Control and Quality Assurance
10.1
Monitoring
The sponsor has ethical, legal, and scientific obligations to follow this trial in accordance 
with established research principles, the ICH E6 GCP: Consolidated Guidance, and 
applicable regulatory requirements and local laws. As part of a concerted effort to fulfill 
these obligations (maintain current personal knowledge of the progress of the trial), the 
sponsor's monitors will visit the site during the trial, as well as communicate frequently 
via telephone, email, and written communications. In addition, all investigators and 
clinical site personnel will undergo initial and ongoing training for this particular trial, 
and this training will be clearly documented.
10.2
Auditing
The sponsor's Quality Assurance Unit (or representative) may conduct trial site audits. 
Audits will include, but are not limited to, Abilify MyCite supply, presence of required 
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documents, the informed consent process, and comparison of case report forms (CRFs)
with source documents. The investigator agrees to participate with audits.
Regulatory authorities may inspect the investigator site during or after the trial. The 
investigator will cooperate with such inspections and will contact the sponsor 
immediately if such an inspection occurs.
11
Ethics and Responsibility
This trial must be conducted in compliance with the protocol, FDA regulations, ICH GCP 
Guideline (E6), international ethical principles derived from the Declaration of Helsinki 
and Council for International Organizations of Medical Science (CIOMS) guidelines, and 
applicable local laws and regulations. Each trial site will seek approval/favorable opinion 
by an IRB according to regional requirements, and the investigator will provide that 
documentation to the sponsor. The IRB will evaluate the ethical, scientific and medical 
appropriateness of the trial. Further, in preparing and handling CRFs, the investigator, 
sub-investigator and their staff will take measures to ensure adequate care in protecting 
subject privacy. To this end, a subject number and subject identification code will be used 
to identify each subject.
Financial aspects, subject insurance and the publication policy for the trial will be 
documented in the agreement between the sponsor and the investigator.
12
Confidentiality
All information generated in this trial will be considered confidential and will not be 
disclosed to anyone not directly concerned with the trial without the sponsor’s prior 
written permission. Subject confidentiality requirements of the region(s) where the trial is 
conducted will be met. However, authorized regulatory officials and sponsor personnel 
(or their representatives) may be allowed full access to inspect and copy the records, 
consistent with local requirements. All IMPs, subject bodily fluids, and/or other materials 
collected shall be used solely in accordance with this protocol, unless otherwise agreed to 
in writing by the sponsor.
Subjects will be identified only by unique subject numbers in CRFs. If further subject 
identification is required, subjects’ full names may be made known to a regulatory 
agency or other authorized officials if necessary, subject to local regulations.
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13
Amendment Policy
The investigator will not make any changes to this protocol without the sponsor’s prior 
written consent and subsequent approval/favorable opinion by the IRB. Any permanent 
change to the protocol, whether an overall change or a change for specific trial site(s), 
must be handled as a protocol amendment. Any amendment will be written by the 
sponsor. Each amendment will be submitted to the IRB, as required by local regulations. 
Except for “administrative” or “non-substantial” amendments, investigators will wait for 
IRB approval/favorable opinion of the amended protocol before implementing the 
change(s). Administrative amendments are defined as having no effect on the safety of 
subjects, conduct or management of the trial, trial design, or the quality or safety of 
Abilify MyCite used in the trial. A protocol change intended to eliminate an apparent 
immediate hazard to subjects should be implemented immediately after agreement by the 
sponsor and investigator, followed by IRB notification within local applicable timelines. 
The sponsor will submit protocol amendments to the applicable regulatory agencies 
within local applicable timelines.
When the IRB, investigators, and/or the sponsor conclude that the protocol amendment 
substantially alters the trial design and/or increases the potential risk to the subject, the 
currently approved written ICF will require similar modification. In such cases, after 
approval/favorable opinion of the new ICF by the IRB, repeat written informed consent 
will be obtained from subjects enrolled in the trial before expecting continued 
participation and before the amendment-specified changes in the trial are implemented.
14
Publication Authorship Requirements
Authorship for any Otsuka-sponsored publications resulting from the conduct of this trial 
will be based on International Committee of Medical Journal Editors (ICMJE) authorship 
criteria (http://www.icmje.org/recommendations). According to ICMJE guidelines, one 
may be considered an author only if the following criteria are met:
1. Substantial contributions to the conception or design of the work; or the 
acquisition, analysis, or interpretation of data for the work; AND
2. Drafting the work or revising it critically for important intellectual content; AND
3. Final approval of the version to be published; AND
4. Agreement to be accountable for all aspects of the work in ensuring that questions 
related to the accuracy or integrity of any part of the work are appropriately 
investigated and resolved.
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All authors must meet the above criteria, and all who qualify for authorship based on the 
above criteria should be listed as authors.
Investigators or other trial participants who do not qualify for authorship may be 
acknowledged in publications resulting from the trial. By agreeing to participate in the 
trial, investigators or other trial participants consent to such acknowledgement in any 
publications resulting from its conduct.
15
References
1
ABILIFY MYCITE (aripiprazole tablets with sensor) US Prescribing 
Information. Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan, Proteus Digital Health, 
Inc., Redwood City, CA, and Otsuka America Pharmaceutical, Inc, Rockville MD; 
2017.
2
Rohatagi S, Profit D, Hatch A, Zhao C, Docherty JP, Peters-Strickland TS. 
Optimization of a Digital Medicine System in Psychiatry. J Clin Psychiatry. 
2016;77(9):e1101-e1107.
3
Peters-Strickland T. A formative usability study of the Otsuka MIND1 prototype by 
subjects with bipolar disorder or major depressive disorder. Otsuka Clinical Study 
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Peters-Strickland T. A multicenter, 8-week, open-label, single-arm, exploratory trial 
to assess the functionality of an integrated call center for the digital medicine system 
by adult subjects with schizophrenia (SCH), major depressive disorder (MDD), or 
bipolar 1 disorder (BP1) who are treated with oral aripiprazole. Otsuka Clinical Study 
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Peters-Strickland T. Phase 1, open-label trial to evaluate the skin irritation potential 
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Peters-Strickland T. A multicenter, 8-week, open-label study to assess usability of the 
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14-220, issued 21 Oct 2015.
7
Data on file. Abilify MyCite.  Human factors engineering/usability engineering 
report: HCP/caregiver interface. NDA 207202. Otsuka Pharmaceutical Development 
& Commercialization, Inc. 2015b.
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Peters-Strickland T, Pestreich L, Hatch A, Rohatagi S, Baker RA, Docherty JP, et al. 
Usability of a novel digital medicine system in adults with schizophrenia treated with 
sensor-embedded tablets of aripiprazole. Neuropsychiatr Dis Treat. 2016;12:2587-94.
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Profit D, Rohatagi S, Zhao C, Hatch A, Docherty JP, Peters-Strickland TS. 
Developing a Digital Medicine System in Psychiatry: Ingestion Detection Rate and 
Latency Period. J Clin Psychiatry. 2016;77(9):e1095-e1100.
10 Kopelowicz A, Baker RA, Zhao C, Brewer C, Lawson E, Peters-Strickland T. A 
multicenter, open-label, pilot study evaluating the functionality of an integrated call 
center for a digital medicine system to optimize monitoring of adherence to oral 
aripiprazole in adult patients with serious mental illness. Neuropsychiatr Dis Treat. 
2017;13:2641-51.
11 Peters-Strickland T, Hatch A, Adenwala A, Atkinson K, Bartfeld B. Human factors 
evaluation of a novel digital medicine system in psychiatry. Neuropsychiatric Disease 
and Treatment. 2018.
12 Cramer JA, Rosenheck R. Compliance with medication regimens for mental and 
physical disorders. Psychiatr Serv. 1998;49:196-201.
13 Proteus Digital Health. Wearable Sensor Investigator’s Brochure, Edition 7. Issued 22 
Mar 2016.
14 Otsuka Pharmaceutical Development and Commercialization. Aripiprazole 
Investigator's Brochure, Edition 22. Issued 07 Aug 2018.
15 Bloss CS, Wineinger NE, Peters M, Boeldt DL, Ariniello L, Kim JY, et al. A 
prospective randomized trial examining health care utilization in individuals using 
multiple smartphone-enabled biosensors. Peer J. 2016;4:e1554.
16 Correll CU. Real-life switching strategies with second-generation antipsychotics. J 
Clin Psychiatry. 2006;67:160-1.
17 Sullivan G, Bienroth M, Jones M, Millar H, Ratna L, Taylor D. Practical prescribing 
with aripiprazole in schizophrenia: consensus recommendations of a UK 
multidisciplinary panel. Curr Med Res Opinion. 2007;23:1733-44.
18 Kay SR, Opler LA, Fiszbein A. Positive and Negative Syndrome Scale (PANSS) 
Rating Criteria. North Tonawanda, NY: Multi-Health Systems; 1999.
19 Naber D, Moritz S, Lambert M, Pajonk F, Holzbach R, Mass R, et al. Improvement of 
schizophrenic patients' subjective well-being under atypical antipsychotic drugs. 
Schizophr Res. 2001;50:79-88.
20 Guy W. ECDEU Assessment Manual for Psychopharmacology. US Department of 
Health, Education, and Welfare publication (ADM) 76-338. Rockville, MD: National 
Institute of Mental Health; 1976.
21 Administration and Policy in Mental Health and Mental Health Services Research. 
2010 Jul; 37(4): 327-333.
22 Oquendo MA, Halberstam B, Mann JJ. Risk factors for suicidal behavior: utility and 
limitations of research instruments. In: First MB, ed. Standardized Evaluation in 
Clinical Practice. Washington, DC: American Psychiatric Publishing; 2003:103-30.
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23 Chue P, Llorca PM, Duchesne I, Leal A, Rosillon D, Mehnert A. Hospitalization 
Rates in Patients During Long-Term Treatment With Long-Acting Risperidone 
Injection. J Applied Research. 2005;5(2):266-74.
24 Kane J, Zhao, C, Johnson B, Baker R, Eramo A, McQuade B, Duca A, Sanchez R, 
Peters-Strickland, T J Med Econ. 2015 Feb;18(2):145-54.
25 Lan KKG and DeMets DL (1983). Discrete sequential boundaries for clinical trials. 
Biometrika, 70, 659-663.
26 Chen JYH, DeMets DL, Lan KKG.(2004). Increasing the sample size when the 
unblinded interim result is promising. Statistics in Medicine, 23(7), 1023-1038.
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Appendix 1
Names of Sponsor Personnel
 PhD
Phone: 
Email: 
Phone: 
Email: 
Phone: 
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Appendix 2
Safety Reporting
Report IREs (SAEs, confirmed pregnancies, and any device-related nonserious AEs [eg, 
skin irritation that is Grade 2 or worse]) to: 
IQVIA Lifecycle Safety
Fax: 
Email: 
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Appendix 3
Abilify MyCite Contents
Abilify MyCite Contents
Abilify MyCite Component
Description
Aripiprazole + IEM
Aripiprazole tablet with sensor will be dispensed to the subjects during 
the trial. Tablets will be taken as prescribed by the healthcare provider, 
with approximately 120 mL of water.
Patch
Patches will be dispensed to a subject for use.
The current Abilify MyCite DW5 patch is a one-piece unit. The patch 
has an adhesive backing that adheres to the user’s body and requires the 
patch to be changed approximately once per week. The updated patch 
(RW2) is made up of two parts; (1) a data pod and (2) an adhesive strip. 
As with the DW5 patch, the adhesive strip needs to be replaced 
approximately once per week, but the data pod is for extended use and 
needs to be inserted into the adhesive strip whenever it is changed. The 
updated patch was designed to eliminate the step of having to press a 
button to pair the patch with the app. The data pod only needs to be 
paired with the app on initial use and does so without the need to press a 
button, unlike the DW5 patch that needed to be paired with every 
application of a new patch. The new pod/strip combination also allows 
for an expanded area for patch placement.
Computing Device & 
Accessories
Subjects will use their own smartphone and required accessories. 
Subjects will be requested to carry their smartphone with them as much 
as possible and to plug in the device at a dedicated location at home 
where they could have easy and frequent access when not being carried. 
The preferred location is on a nightstand or a location immediately 
adjacent to where the subject sleeps.
Abilify MyCite Reference 
Guide
A printed reference guide will provide explicit directions for normal use 
and troubleshooting.
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Version 2.0, 11 Feb 2019
Appendix 4
Protocol Amendment
Amendment Number:
1
Issue Date:
11 Feb 2019
PURPOSE:
The protocol was amended to revise the secondary and exploratory endpoints and to add 
an exploratory endpoint for the 
. In addition, minor 
clarifications to the monthly assessments and corresponding trial days, assessment 
window, endpoints, inclusion and exclusion criteria, schedule of assessments, and ECG 
assessment language were incorporated.
BACKGROUND:
The intention of this protocol amendment was to revise the trial endpoints to better match 
the intended study objectives. These changes to clinical trial protocol 031-201-00301, 
issued 04 Jan 2019, are listed below in detail.
MODIFICATIONS TO PROTOCOL:
Sectional Revisions:
Description of Change
Sections Affected by Change
Clarified assessment window of - 3/ + 2 days for 
Months 1 through 6 globally
Global change
Clarified monthly assessments will follow a 28-day 
schedule and revised study days accordingly
Protocol synopsis
Section 3.1 Type/Design of Trial
Figure 3.1-1 Trial Design Schematic
Section 3.5.3 Exploratory Endpoints
Table 3.7-1 Schedule of Assessments
Section 3.7.1.3 Prospective Phase (6 Months)
Clarified in the inclusion criteria that caregiver 
support may be utilized throughout the trial and that 
the caregiver/support person will be asked (where 
applicable) to provide feedback via the Caregiver 
Involvement Scale
Protocol synopsis
Table 3.4.2-1 Inclusion Criteria
Removed exclusion criterion #4 regarding 
hospitalization during the screening period
Protocol synopsis
Table 3.4.3-1 Exclusion Criteria
Clarified the secondary endpoint for the trial
Protocol synopsis
Section 3.5.2 Secondary Endpoint
Section 7.4.2 Secondary Endpoint Analysis
Revised several secondary endpoints to exploratory 
endpoints and clarified the exploratory endpoint 
analysis for the 
Protocol synopsis
Section 3.5.3 Exploratory Endpoints
Section 7.4.3 Exploratory Endpoint Analysis
Removed Abilify MyCite product, supplies, and 
patch dispensation at Month 6/ET
Table 3.7-1 Schedule of Assessments
Section 3.7.1.3.5 Month 6/Early Termination Visit
Clarified language regarding ECG assessments
Section 3.7.3.4 Electrocardiogram Assessments
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ADDITIONAL RISK TO THE SUBJECT:
There is no additional risk to the subjects.
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Agreement
I, the undersigned principal investigator, have read and understand the protocol (including the 
Investigator's Brochure) and agree that it contains all the ethical, legal and scientific information 
necessary to conduct this trial in accordance with the principles of GCPs and as described herein 
and in the sponsor's (or designee's) Clinical Trial Agreement.
I will provide copies of the protocol to all physicians, nurses, and other professional personnel to 
whom I delegate trial responsibilities. I will discuss the protocol with them to ensure that they are 
sufficiently informed regarding the IND, aripiprazole, the concurrent medications, the efficacy and 
safety parameters and the conduct of the trial in general. I am aware that this protocol must be 
approved by the Institutional Review Board (IRB) responsible for such matters in the clinical trial 
facility where aripiprazole will be tested prior to commencement of this trial. I agree to adhere 
strictly to the attached protocol (unless amended in the manner set forth in the sponsor's Clinical 
Trial Agreement, at which time I agree to adhere strictly to the protocol as amended).
I understand that this IRB-approved protocol will be submitted to the appropriate regulatory 
authority/ies by the sponsor. I agree that clinical data entered on case report forms by me and my 
staff will be utilized by the sponsor in various ways, such as for submission to governmental 
regulatory authorities and/or in combination with clinical data gathered from other research sites, 
whenever applicable. I agree to allow sponsor and designee monitors and auditors full access to 
all medical records at the research facility for subjects screened or enrolled in the trial.
I agree to await IRB approval before implementation of any substantial amendments to this 
protocol. If, however, there is an immediate hazard to subjects, I will implement the amendment 
immediately, and provide the information to the IRB within the required local applicable timelines. 
Administrative changes to the protocol will be transmitted to the IRB for informational purposes 
only, if required by local regulations.
I agree to provide all subjects with ICFs, as required by the applicable regulations and by ICH 
guidelines. I agree to report to the sponsor any adverse experiences in accordance with the terms 
of the sponsor's Clinical Trial Agreement and the relevant regional regulation(s) and guideline(s). 
I further agree to provide all required information regarding financial certification or disclosure to 
the sponsor for all investigators and sub-investigators in accordance with the terms of the 
relevant regional regulation(s). I understand that participation in the protocol involves a 
commitment to publish the data from this trial in a cooperative publication before publication of 
efficacy and safety results on an individual basis may occur, and I consent to be acknowledged in 
any such cooperative publications that result.
____________________________
_____________________________
___________
Principal Investigator Print Name
Signature
Date
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16.1.1 Protocol and Protocol Amendments
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This page is a manifestation of an electronically captured signature
SIGNATURE PAGE
Document Name: 031-201-00301 Protocol Amendment 1
Document Number: 1000021943
Document Version: 3.0
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:min) -
UTC timezone
Clinical Approval
11-Feb-2019
19:25:59
Biostatistics Approval
11-Feb-2019
17:03:20
Clinical Study Report 031-201-00301
16.1.1 Protocol and Protocol Amendments
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confidential information and should not be duplicated or re-distributed without prior written consent of Otsuka.
95