Conditions: Schizophrenia Bipolar 1 Disorder Major Depressive Disorder
Keywords: Digital Medicine System
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 2
Healthy volunteers: no

Brief summary:
The primary objective of this pragmatic clinical trial (Main Study) was to assess the difference between all-cause hospitalizations in participants using Abilify MyCite versus virtual matched controls. In addition, secondary and exploratory objectives were to assess medication adherence, healthcare utilization and costs, and patient-reported outcomes.

Detailed description:
This was a phase 4, open-label, prospective, pragmatic clinical trial to assess the difference between all-cause hospitalizations in participants using Abilify MyCite (for Months 1-3, then prohibited for Months 4-6) versus virtual matched controls from baseline to Day 180. Virtual matched controls were to receive treatment as usual (that is, any product other than Abilify MyCite, which was oral aripiprazole or any other product). Eligible participants entered a screening period of up to 13 days. For participants enrolling into the study, those not on aripiprazole at screening used the screening period for conversion to aripiprazole from other antipsychotics. Virtual matched controls were not to be enrolled into the study, but identified from health insurance claims data and matched to the enrolled Abilify MyCite participants at the end of the study for analysis.

After the visit at Day 180, a second, optional interventional period (up to 6 months of Abilify MyCite) could have been initiated per the joint decision of the participants with their study physician; participants in this second, optional interventional period were to have a visit at Day 360. During this second, optional interventional period, participants may have started and stopped Abilify MyCite as clinically indicated.

A parallel exploratory study that would utilize a different set of physicians and participants from the main study was planned; however, that study was never initiated.

Arms:
arm 1: Participants received Abilify MyCite during Months 1-3. During Months 4-6 use of Abilify MyCite was to be prohibited. Thereafter, at Day 180, a second, optional interventional period (up to 6 months of Abilify MyCite) could have been initiated per the joint decision of the participants with their study physician. arm 2: Virtual matched controls were to receive treatment as usual (that is, any product other than Abilify MyCite, which could have been oral aripiprazole or any other product) throughout the duration of the trial. Virtual matched controls were not to be enrolled into the study, but identified from health insurance claims data and matched to the enrolled Abilify MyCite participants at the end of the study for analysis.

Interventions: intervention 1: Abilify MyCite - Digital Medicine System intervention 2: Aripiprazole or other oral antipsychotics
Intervention descriptions: intervention 1: 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 participants, healthcare providers, and potential caregivers. Abilify MyCite is intended to track drug ingestion and is indicated for the treatment of adults with schizophrenia (SCH), bipolar 1 disorder (BP1) (acute treatment of adults with manic and mixed episodes or maintenance treatment of adults), and adjunctive treatment of adults with major depressive disorder (MDD). intervention 2: For the treatment of adults with SCH, BP1 (acute treatment of adults with manic and mixed episodes or maintenance treatment of adults), and adjunctive treatment of adults with MDD.

Protocol document:
Prot_000.pdf: 
Protocol 316-13-217 
Confidential - Proprietary Information 
Protocol number: 316-13-217
Document title: A Multicenter, 180-day Pragmatic Clinical Trial to 
Measure the Difference in All-cause Hospitalizations for Patients 
Who Are Using Abilify MyCite Versus Virtual Matched Controls in 
Adults With Schizophrenia, Bipolar 1 Disorder, and Major 
Depressive Disorder  
Version number: 1.0
Date of the document: 08 March 2018
NCT number:    NCT03643159 


Otsuka Pharmaceutical
Development & Commercialization, Inc.
Medical Device
Abilify MyCite (OPC-14597 Digital, aripiprazole tablet with sensor)
PROTOCOL
A Multicenter, 180-day Pragmatic Clinical Trial to Measure the Difference in 
All-cause Hospitalizations for Patients who are Using Abilify MyCite versus 
Virtual Matched Controls in Adults with Schizophrenia, Bipolar 1 Disorder, and 
Major Depressive Disorder 
Protocol No. 316-13-217
NDA No. 207202
CONFIDENTIAL – PROPRIETARY INFORMATION
Clinical Development Phase:
4 
Study Type:
Pragmatic Clinical Trial 
Sponsor:
Otsuka Pharmaceutical Development & 
Commercialization, Inc.
2440 Research Boulevard
Rockville, Maryland 20850, United States
Sponsor Representatives: 
Associate Director, 
Global Clinical Development:
Phone: 
E-mail: 
Associate Director,
Clinical Management:
Phone: 
E-mail: 
Senior Manager,
Clinical Management:
Phone: 
Immediately Reportable Event:
Global Safety and Pharmacovigilance
Fax: 
E-mail:
 
Issue Date:
08 Mar 2018
PPD
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Protocol Synopsis
Name of Company: Otsuka Pharmaceutical
Development & Commercialization, Inc.
Name of Product: Medical Device Abilify MyCite 
(OPC-14597 Digital; aripiprazole tablet with sensor)
Protocol No. 316-13-217
Protocol Title:
A Multicenter, 180-day Pragmatic Clinical Trial to Measure 
the Difference in All-cause Hospitalizations for Patients who 
are Using Abilify MyCite versus Virtual Matched Controls in 
Adults with Schizophrenia, Bipolar 1 Disorder, and Major 
Depressive Disorder 
Clinical Development 
Phase:
4
Study Type:
Pragmatic Clinical Trial
Indication: 
Adults with schizophrenia (SCH), bipolar 1 disorder (BP1), 
and major depressive disorder (MDD)
Objective(s):
The primary objective of this study is to assess the difference 
in all-cause hospitalizations between patients using Abilify 
MyCite versus virtual matched controls at Day 180.
In addition, secondary and exploratory objectives will assess 
medication adherence, healthcare utilization and costs, and 
patient-reported outcomes.
Study Design/
Methodology:
Main Study
This is a phase 4, open-label, prospective, pragmatic clinical 
trial to assess the difference between all-cause hospitalizations
in patients using Abilify MyCite (for Months 1-3, then 
prohibited for Months 4-6) versus virtual matched controls 
from baseline to Day 180. Virtual matched controls 
 
 would be receiving treatment 
as usual (ie, any product other than Abilify MyCite, which 
may be oral aripiprazole or any other product).
Eligible patients will enter a screening period of up to 13 days.
For patients enrolling into the study, those not on aripiprazole 
at screening will use the screening period for conversion to 
aripiprazole from other antipsychotics according to the 
approved labels. At the baseline visit (which may be the same 
visit as the screening visit), Abilify MyCite onboarding will be 
provided in the office, with commercial informational 
materials and additional call center support; then, patients will 
initiate 3 months of treatment with Abilify MyCite at the 
baseline visit. 
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During the following 3 months (Months 4-6), use of Abilify 
MyCite will be prohibited (and the patient continues with oral 
aripiprazole or other appropriate treatment, per routine clinical 
care). The primary endpoint will be assessed at Day 180.
After the visit at Day 180, a second, optional interventional 
period (up to 6 months of Abilify MyCite) may be initiated per 
the joint decision of the patients with their study physician;
patients in this second, optional interventional period will have 
a visit at Day 360 (in addition to their regular visits as 
clinically indicated). During this second, optional 
interventional period, patients may start and stop Abilify 
MyCite as clinically indicated.
Enrolled patients will be matched to a virtual control group 
identified from 
 in a 1:3 ratio 
(enrolled patients on Abilify MyCite treatment versus virtual 
matched controls).
 
the matching will be performed after the Abilify 
MyCite arm has been completed. 
Exploratory Study
In addition, there will be a parallel exploratory study, which 
will utilize a different set of physicians and patients from the 
main study. Results from the exploratory study will be 
analyzed separately from the main study results.
Procedures for the exploratory study will be similar to those in 
the main study (see above), with the exception that there will 
be 1-month intervals of Abilify MyCite use (and 1-month 
intervals of prohibition of Abilify MyCite use). During periods 
of nonuse of Abilify MyCite, the patient continues with oral 
aripiprazole treatment, per routine clinical care.
In the exploratory study, each patient will receive Abilify 
MyCite per 1 one of 2 sequences over a 360-day period:

Sequence 1: Only in Months 1, 2, 5, and 10.

Sequence 2: Only in Months 1, 4, 7, and 10.
Sites will be randomized to 1 of the 2 sequences.
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For this exploratory study, the site visits will be at screening, 
baseline (which may be the same day as the screening visit), 
Day 180, and Day 360; additional visits are to occur as 
clinically indicated. The exploratory arm will begin after the 
main study is enrolled at approximately 50% (ie, staggered 
start).
Patient Population:
In both the main and exploratory studies, participants will be 
adult patients with SCH, BP1, or MDD who, within 60 days 
prior to study enrollment, had a hospitalization (all-cause or 
psychiatric, ie, for any reason) or at least 1 psychiatric partial 
hospital admission. To achieve balanced enrollment of the 
targeted diagnoses, a minimum enrollment of each diagnosis 
will be 25% for each study.
The main study will enroll approximately 640 total patients.
The exploratory study will enroll approximately 150 adult 
patients (75 per sequence), utilizing different sites from the 
main study (ie, a different set of patients and physicians).
Inclusion/Exclusion
Criteria:
Inclusion criteria

Patients are actively enrolled in an Anthem-affiliated 
commercial, Medicaid, or Medicare health plan with 
medical and pharmacy benefits. 

Male and female patients between the ages of 18 and 
63 years, inclusive at the time of consent.

Patients must have a smartphone with data plan. 

Patients must have a current diagnosis of SCH, BP1, or 
MDD.

Patients currently prescribed aripiprazole, or appropriate 
for aripiprazole treatment.

Within 60 days prior to study enrollment, patients are 
required to have had a hospitalization (all cause or 
psychiatric) or at least 1 psychiatric partial hospital 
admission. 

Patients are deemed appropriate, per the study physician 
judgment, to use Abilify MyCite per the package insert and 
to enter this interventional study.

Patients must be able to read and understand English.


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Exclusion criteria

Any patient who participated in another clinical trial within 
30 days of enrollment into the current study.

Females who are breast-feeding and/or who are pregnant at 
the time of study enrollment, or who plan to become 
pregnant during the study.

Patients who are currently being treated with a long-acting 
injectable antipsychotic.
Study Sites
Approximately 100 overall (main plus exploratory studies)
Device, Dose,
Dosage Regimen,
Treatment Period,
Formulation, Mode
of Administration:
Abilify MyCite® tracks drug ingestion and is composed of the 
following components:

Aripiprazole embedded with an ingestible event marker 
(IEM) sensor (Abilify MyCite);

MyCite® Patch (wearable sensor) that detects the signal 
from the IEM sensor after ingestion and transmits data to a 
smartphone;

MyCite App, a smartphone application (app), which is 
used with a compatible smartphone to display medication 
ingestion information for the patient;

Web-based portal or dashboard for healthcare providers 
(HCPs) and caregivers. 
The treatment medication dose decision will be determined by 
the study physicians independent from the protocol.
Treatment period - Main Study
Patients receive treatment with Abilify MyCite during Month 1 
through Month 3. During Months 4 through 6, use of Abilify 
MyCite will be prohibited (and the patient continues with oral 
aripiprazole or other appropriate treatment, per routine clinical 
care). Thereafter, at Day 180, a second, optional interventional 
period (up to 6 months of Abilify MyCite) may be initiated per 
the joint decision of the patients with their study physician.
Treatment period - Exploratory Study
In the exploratory study, each patient will receive Abilify 
MyCite per 1 one of the 2 sequences over a 360-day period:

Sequence 1: Only in Months 1, 2, 5, and 10.

Sequence 2: Only in Months 1, 4, 7, and 10.


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Study Assessments
 
 
 
 
 
 
Criteria for 
Evaluation:
Primary Endpoint (Main Study)
Difference in the proportion of patients with all-cause 
hospitalizations for patients using Abilify MyCite versus 
virtual matched controls from baseline to Day 180.
Secondary Endpoint (Main Study)
Difference between groups (Abilify MyCite versus virtual 
matched controls) in the proportion of patients with at least 
80% proportion of days covered (PDC) (with antipsychotic 
medication) from baseline to Day 180.
 
 
 
 
 
 
 
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Statistical Methods:
For the main study, the primary analysis will be a comparison 
of proportions between the Abilify MyCite cohort and virtual 
matched control group based on standard formulas.
Study Duration:
The main study, the expected maximum study duration per 
patient from screening to their last visit will be 373 days 
(ie, up to 13 days screening, plus an expected maximum of 
360 days in the study if the patient participates in the optional 
second interventional period).
For the exploratory study, the expected maximum study
duration per patient will be 373 days (ie, the same as the main 
study).
Since the main and exploratory studies will utilize different 
physicians and patients, the expected maximum study duration 
for any patient will be 373 days. 
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Table of Contents
Protocol Synopsis...........................................................................................2
Table of Contents...........................................................................................9
List of In-text Tables ...................................................................................13
List of In-text Figures..................................................................................14
List of Appendices........................................................................................15
List of Abbreviations and Definitions of Terms .......................................16
1
Introduction ........................................................................................17
1.1
Rationale for Development of Abilify MyCite .................................................17
1.2
Components.......................................................................................................19
2
Study Rationale and Objectives ........................................................21
2.1
Study Rationale .................................................................................................21
2.2
Study Objectives................................................................................................21
3
Study Design........................................................................................22
3.1
Type/Design of Study........................................................................................22
3.1.1
Main Study......................................................................................................25
3.1.2
Exploratory Study...........................................................................................26
3.2
Study Population ...............................................................................................26
3.2.1
Main Study......................................................................................................26
3.2.2
Exploratory Study...........................................................................................27
3.3
Eligibility Criteria for Physicians and Patients (Main and Exploratory 
Studies)..............................................................................................................27
3.3.1
Informed Consent ...........................................................................................27
3.3.2
Physician Practice Eligibility..........................................................................27
3.3.3
Patient Recruitment and Eligibility ................................................................28
3.3.4
Patient Inclusion Criteria ................................................................................28
3.3.5
Patient Exclusion Criteria...............................................................................28
3.4
Outcome Variables............................................................................................29
3.4.1
Primary Endpoint (Main Study) .....................................................................29
3.4.2
Secondary Endpoints (Main Study)................................................................29


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3.4.3
Exploratory Endpoints (Main Study)..............................................................29
3.4.4
Endpoints for the Exploratory Study..............................................................30
3.5
Study Procedures...............................................................................................30
3.5.1
Main Study: Schedule of Assessments...........................................................30
3.5.1.1
35
3.5.1.2
Main Study: Enrollment Procedures...........................................................35
3.5.1.3
Main Study: Screening................................................................................35
3.5.1.4
Main Study: Baseline..................................................................................35
3.5.1.5
Main Study: Treatments..............................................................................35
3.5.1.6
Main Study: Interventional Phase (Day 1 to Day 180)...............................36
3.5.1.7
Main Study: Day 180 Mid-study (or End-of-study) Visit...........................36
3.5.1.8
Main Study: Second Interventional Period (Day 180 to Day 360).............36
3.5.1.9
37
3.5.2
Exploratory Study: Schedule of Assessments ................................................37
3.5.3
Assessments (Main and Exploratory Studies)................................................41
3.5.3.1
Adverse Events............................................................................................41
3.5.3.2
......................41
3.5.3.3
41
3.5.3.4
41
3.5.3.5
42
3.5.3.6
42
3.5.4
Virtual Matched Control Group (Main Study Only)......................................42
3.5.5
End of Study ...................................................................................................43
3.6
Stopping Rules, Withdrawal Criteria, and Procedures......................................43
3.6.1
Entire Study ....................................................................................................43
3.6.2
Individual Site.................................................................................................43
3.6.3
Individual Patient............................................................................................43
3.6.4
 
44
3.7
Protocol Deviations...........................................................................................44
4
Reporting of Adverse Events.............................................................44
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4.1
Definitions.........................................................................................................45
4.1.1
Drug-related Serious Adverse Events.............................................................45
4.1.2
Device-related Serious Adverse Events..........................................................45
4.1.3
Nonserious Adverse Events............................................................................46
4.1.4
Immediately Reportable Event .......................................................................46
4.1.5
Abnormal Clinical Laboratory Test Changes.................................................47
4.1.6
Severity...........................................................................................................47
4.1.7
Abilify MyCite Causality ...............................................................................47
4.2
Eliciting and Reporting Serious Adverse Events ..............................................48
4.3
Immediately Reportable Events ........................................................................48
4.4
Potential Drug-induced Liver Injury.................................................................48
4.5
Pregnancy..........................................................................................................49
4.6
Follow-up of Serious Adverse Events...............................................................50
4.6.1
Follow-up and Reporting of Serious Adverse Events Occurring after 
Last Scheduled Contact ..................................................................................50
5
Data Collection....................................................................................50
5.1
Data Sources......................................................................................................50
5.2
Electronic Case Report Forms and Electronic Data Collection ........................51
6
Quality Control and Quality Assurance...........................................51
6.1
Monitoring.........................................................................................................51
6.2
Auditing/Inspections .........................................................................................51
7
Statistical Methods and Planned Analyses.......................................52
7.1
Sample Size.......................................................................................................52
7.2
Analysis of Demographic and Baseline Characteristics....................................52
7.3
Effectiveness Analyses......................................................................................53
7.3.1
Primary Endpoint............................................................................................53
7.3.2
Secondary Endpoint........................................................................................54
7.3.3
Exploratory Endpoints....................................................................................54
7.4
Safety Analyses .................................................................................................54
7.5
Other Analyses ..................................................................................................54
7.6
Source Documents.............................................................................................54


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7.7
Data Collection..................................................................................................55
7.8
File Management and Records Retention at the Study Site..............................55
8
Ethics and Responsibility...................................................................55
8.1
Institutional Review Board / Independent Ethics Committee...........................55
9
Confidentiality ....................................................................................55
9.1
Publication of Study Results .............................................................................56
10
Amendment Policy..............................................................................56
11
References............................................................................................56
Appendices....................................................................................................58


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List of In-text Tables
Table 1.2-1
Overview of Abilify MyCite System.............................................20
Table 3.3.4-1
Inclusion Criteria ...........................................................................28
Table 3.3.5-1
Exclusion Criteria ..........................................................................28
Table 3.5.1-1
Main Study: Schedule of Assessments (for Patients Enrolled 
at Sites)
................................................................................32
Table 3.5.2-1
Exploratory Study: Schedule of Assessments (for Patients 
Enrolled at Sites)............................................................................39


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List of In-text Figures
Figure 1.2-1
Abilify MyCite Components..........................................................19
Figure 3.1-1
Overview of Pragmatic Study 316-13-217: Main Study and 
Exploratory Study..........................................................................22
Figure 3.1-2
Study Design Schematic (Main Study)..........................................23
Figure 3.1-3
Study Design Schematic (Exploratory Study) ...............................24


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List of Appendices
Appendix 1
Names of Sponsor Personnel .........................................................58
Appendix 2
Safety Reporting ............................................................................59
Appendix 3
Abilify MyCite Contents................................................................60
Appendix 4
Patient Usability and Satisfaction Scale (v2.0)..............................61
Appendix 5
Physician Utility Survey (v2.0)......................................................64
Appendix 6
Caregiver/Support Person Involvement Scale (v2.0).....................68
Appendix 7
Patient Activation Measure - Mental Health Scale........................70
Appendix 8
PROMIS Ability to Participate in Social Roles and Activities 
– Short Form 8a .............................................................................73
Appendix 9
Skin Irritation Scoring System.......................................................74


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List of Abbreviations and Definitions of Terms
Abbreviation
Definition
AE
Adverse event
DILI
Drug-induced liver injury
eCRF
Electronic case report form
EDC
Electronic data capture
ET
Early termination
FDA
United States Food and Drug Administration
FOCBP
Females of childbearing potential
HA
Alternative hypothesis
HCP
Healthcare provider
HIPAA
Health Insurance Portability and Accountability Act
ICF
Informed consent form
ID
Identifier
IEC
Independent ethics committee
IEM
Ingestible event marker
IRB
Institutional review board
IRE
Immediately reportable event
MDD
Major depressive disorder
PDC
Proportion of days covered
 
OPDC
Otsuka Pharmaceutical Development & Commercialization, Inc.
SAE
Serious adverse event
SAP
Statistical analysis plan
SCH
Schizophrenia
Seq
Sequence
ULN
Upper limit of normal
US
United States
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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 (SCH);

Treatment of bipolar 1 disorder (BP1): 

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 embedded with an IEM sensor (Abilify MyCite);

MyCite® Patch (wearable sensor) that detects the signal from the IEM sensor after 
ingestion and transmits data to a smartphone;

MyCite App, a smartphone application (app), which is used with a compatible 
smartphone to display medication ingestion information for the patient;

Web-based portal or dashboard for HCPs and caregivers.
This trial will utilize commercially available Abilify MyCite.
The Abilify MyCite system has been tested in patients 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 patients 
and HCPs/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
 
1.1
Rationale for Development of Abilify MyCite
The Abilify MyCite system is a drug-device combination product comprised of 
aripiprazole (an atypical antipsychotic) tablets embedded with a sensor that 
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communicates with a patch (wearable sensor) and a medical software application with 
collected information (ingestion, mood, activity, rest) tracked and summarized for 
patients, HCPs, and potentially caregivers. Abilify MyCite is intended to track drug 
ingestion and is indicated for the treatment of adults with SCH, BP1 (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 patient 
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 patients 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 patients.
Currently available methods for monitoring adherence have limitations; as such, an 
unmet need exists for a simple, accurate solution for adherence monitoring to enable 
HCPs to objectively measure whether a patient was adherent to treatment. Increasing 
HCP awareness of patient nonadherence and its role in suboptimal response may allow 
for better treatment decision making and allow an opportunity for more HCP/patient 
engagement in care. The available evidence suggests that patient engagement or 
activation in serious mental illness, while not a main focus in clinical practice, may 
provide substantial benefit to patient health outcomes, including management of 
comorbid conditions, and should be encouraged. 
The Abilify MyCite system may be used by HCPs 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 HCPs 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 patients, 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 patient and HCP (and caregivers with patient 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 patient 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 


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antipsychotics and antidepressants, respectively, compared with an adherence rate of 76% 
for nonpsychiatric medications.12 This finding is problematic due to the relationship 
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
1.2
Components
 an overview of the 
Abilify MyCite system is shown in Table 1.2-1.
Also see Appendix 3 (Abilify MyCite Contents).
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Table 1.2-1
Overview of Abilify MyCite System
Characteristic
Description
Components 

Aripiprazole tablet embedded with an IEM sensor (Abilify MyCite)

MyCite Patch (wearable sensor) that detects the signal from the IEM sensor after 
ingestion and transmits data to a smartphone

MyCite App (a smartphone application [app] which is used with a compatible 
smartphone to display information for the patient)

Web-based portal for HCPs 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 SCH; treatment of BP1 (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.
Limitations of 
use

The ability of Abilify MyCite to improve patient 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.
Also see Appendix 3 (Abilify MyCite Contents).
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 patient 
and to web-based software that can display information for an HCP or caregiver. The 
Abilify MyCite system is composed of the following components (Figure 1.2-1 and
Table 1.2-1.)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 MyCite Patch (wearable 
sensor) to track aripiprazole ingestion.

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 patient 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.

MyCite App (a smartphone app which is used with a compatible smartphone to 
display information for the patient) to allow patients to review their medication 
ingestion as well as enter their behavioral data (patient rated mood and quality of 


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rest). These data can be shared with healthcare providers (HCPs) and caregivers with 
the patient’s consent.

Web-based portal for HCPs and caregivers provides an interface to review data 
shared by a patient.
2
Study Rationale and Objectives
2.1
Study 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 patients and 
consumers that may improve health management and medication compliance.14
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 patient’s torso. The patch transmits data to the 
patient’s mobile device (ie, smartphone), which uploads data to a secure, cloud-based 
server. Use of Abilify MyCite will allow patients to view their aripiprazole ingestion data 
on their mobile device; in this way, the patient can learn about their medication-ingestion 
patterns, which could enable greater patient awareness and self-management of their 
disease.
In addition, the patients’ HCPs and elected caregivers can view data via a web-based 
portal served by the cloud-based server.1 With Abilify MyCite tracking drug ingestion, 
all-cause hospitalizations (ie, hospitalizations for any reason) should be reduced when 
compared to virtual matched controls; this reduction is anticipated to be driven by an 
improvement in timely and appropriate treatment decisions based on objective data. 
The main and exploratory studies will explore different use-patterns of Abilify MyCite to 
determine the durability of the system effect over time.
2.2
Study Objectives
The primary objective of this study is to assess the difference in all-cause hospitalizations 
between patients using Abilify MyCite versus virtual matched controls at Day 180. 
In addition, secondary and exploratory objectives will assess medication adherence, 
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3
Study Design
3.1
Type/Design of Study
An overview of the main and exploratory studies is provided in Figure 3.1-1.
Study design schematics are provided in Figure 3.1-2 (main study) and in Figure 3.1-3
(exploratory study). 
Figure 3.1-1
Overview of Pragmatic Study 316-13-217: Main Study and 
Exploratory Study
The exploratory arm will begin after the main study is enrolled at approximately 50% (ie, staggered 
start). Virtual matched controls 
 would be receiving 
treatment as usual (ie, any product other than Abilify MyCite, which may be oral aripiprazole or any 
other product).
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Figure 3.1-2
Study Design Schematic (Main Study)
The second, optional interventional period (up to 6 months of Abilify MyCite) may be initiated per the joint decision of the patients with their study physician.
During this second, optional interventional period, patients may start and stop Abilify MyCite as clinically indicated.


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Figure 3.1-3
Study Design Schematic (Exploratory Study)


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3.1.1
Main Study
The study design schematic for the main study in provided in Figure 3.1-2.
This is a phase 4, open-label, prospective, pragmatic clinical trial to assess the difference 
between all-cause hospitalizations in patients using Abilify MyCite (for Months 1-3, then 
prohibited for Months 4-6) versus virtual matched controls from baseline to Day 180. 
Virtual matched controls 
 would be receiving 
treatment as usual (ie, any product other than Abilify MyCite, which may be oral 
aripiprazole or any other product).
Eligible patients will enter a screening period of up to 13 days. For patients enrolling into 
the study, those not on aripiprazole at screening will use the screening period for 
conversion to aripiprazole from other antipsychotics according to the approved labels. At 
the baseline visit (which may be the same visit as the screening visit), Abilify MyCite 
onboarding will be provided in the office, with commercial informational materials and 
additional call center support; then, patients will initiate 3 months of treatment with 
Abilify MyCite at the baseline visit.
During the following 3 months (Months 4 through 6), use of Abilify MyCite will be 
prohibited (and the patient continues with oral aripiprazole or other appropriate treatment, 
per routine clinical care). The primary endpoint will be assessed at Day 180. The final 
study visit will be on Day 180 for patients not continuing in the second, optional 
interventional period.
After the visit at Day 180, a second, optional interventional period (up to 6 months of 
Abilify MyCite) may be initiated per the joint decision of the patients with their study 
physician; patients in this second, optional interventional period will have a visit at 
Day 360 (in addition to their regular visits as clinically indicated). During this second, 
optional interventional period, patients may start and stop Abilify MyCite as clinically 
indicated.
Enrolled patients will be matched to a virtual control group identified from 
 
 in a 1:3 ratio (enrolled patients on Abilify MyCite treatment versus 
virtual matched controls).
 
the matching will be performed after the 
Abilify MyCite arm has been completed. 
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3.1.2
Exploratory Study
The study design schematic for the parallel exploratory study in provided in Figure 3.1-3. 
The parallel exploratory study will utilize a different set of physicians and patients from 
the main study. Results from the exploratory study will be analyzed separately from the 
main study results.
Procedures for the exploratory study will be similar to those in the main study 
(see Section 3.1.1), with the exception that there will be 1-month intervals of Abilify 
MyCite use (and 1-month intervals of prohibition of Abilify MyCite use), as diagrammed 
in the study schematic (Figure 3.1-3). During periods of nonuse of Abilify MyCite, the 
patient continues with oral aripiprazole, per routine clinical care.
In the exploratory study, each patient will receive Abilify MyCite per 1 one of 
2 sequences over a 360-day period:

Sequence 1: Only in Months 1, 2, 5, and 10.

Sequence 2: Only in Months 1, 4, 7, and 10.
Sites will be randomized to 1 of the 2 sequences.
For this exploratory study, the site visits will be at screening, baseline (which may be the 
same day as the screening visit), Day 180, and Day 360; additional visits are to occur as
clinically indicated. The exploratory arm will begin after the main study is enrolled at 
approximately 50% (ie, staggered start).
3.2
Study Population
Enrollment is described in Section 3.2.1 (main study) and Section 3.2.2 (exploratory 
study).
For information on the virtual matched control group, see Section 3.5.4.
3.2.1
Main Study
The main study will enroll approximately 640 adult patients with SCH, BP1, or MDD 
who, within 60 days prior to study enrollment, had a hospitalization (all-cause or 
psychiatric, ie, for any reason) or at least 1 psychiatric partial hospital admission. To 
achieve balanced enrollment of the targeted diagnoses, a minimum enrollment of each 
diagnosis will be 25% or approximately 160 total patients.


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3.2.2
Exploratory Study
The exploratory study will utilize different physicians and patients from the main study.
The exploratory study will enroll approximately 150 adult patients (75 per sequence) with 
SCH, BP1, or MDD who, within 60 days prior to study enrollment, had a hospitalization 
(all-cause or psychiatric) or at least 1 psychiatric partial hospital admission. 
As with the main study, to achieve balanced enrollment of the targeted diagnoses, a 
minimum enrollment of each diagnosis will be 25%, or approximately 37 patients. The 
exploratory arm will begin after the main study is enrolled at approximately 50% 
(ie, staggered start).
3.3
Eligibility Criteria for Physicians and Patients (Main and 
Exploratory Studies)
All of Section 3.3 applies to both the main study and the exploratory study. The 
procedures refer to physicians and patients at the study sites; for information on the
virtual matched control group, see Section 3.5.4.
3.3.1
Informed Consent
An informed consent form (ICF) fully describing the purpose, procedures, and potential 
risks and benefits of the study will be developed and approved by the Institutional 
Review Board / Independent Ethics Committee (IRB/IEC) prior to study initiation. The 
study physician must ensure that each study patient is fully informed of the study and 
authorizes release of health information prior to study enrollment. Written informed 
consent will be obtained prior to initiation of any study-related procedures. The patient 
will receive a copy of the signed ICF. The study physician will retain the original signed 
ICF for each patient. The IRB/IEC must prospectively approve the ICF and any changes 
to the ICF during the course of the study before use.
3.3.2
Physician Practice Eligibility
Enrollment of approximately 100 physician sites overall (ie, main study plus exploratory
study) from the Anthem Network of providers in the United States (US) is planned for 
this study. HealthCore will identify potential physicians for the study by analyzing 
 
 to 
identify physicians who provide care for a high volume of patients who potentially meet 
basic inclusion criteria sufficient to support study enrollment goals.
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Physicians (and patients) in the main study will be distinct from those in the exploratory 
study.
3.3.3
Patient Recruitment and Eligibility
Patients will be recruited for enrollment when they interact with their physician as part of 
their standard of care. Eligible participants include adult patients with a current diagnosis 
of SCH, BP1, or MDD being treated with aripiprazole, or for whom aripiprazole 
treatment would be appropriate, as determined by the treating physician. Patients must 
also meet all of the inclusion criteria (Section 3.3.4) and none of the exclusion criteria 
(Section 3.3.5).
3.3.4
Patient Inclusion Criteria
For enrollment into the study, patients are required to meet the following inclusion 
criteria: 
Table 3.3.4-1
Inclusion Criteria
1.
Patients are actively enrolled in an Anthem-affiliated commercial, Medicaid, or Medicare health 
plan with medical and pharmacy benefits. 
2.
Male and female patients between the ages of 18 and 63 years, inclusive at the time of consent.
3.
Patients must have a smartphone with data plan. 
4.
Patients must have a current diagnosis of SCH, BP1, or MDD.
5.
Patients currently prescribed aripiprazole, or appropriate for aripiprazole treatment.
6.
Within 60 days prior to study enrollment, patients are required to have had a hospitalization (all 
cause or psychiatric) or at least 1 psychiatric partial hospital admission.
7.
Patients are deemed appropriate, per the study physician judgment, to use Abilify MyCite per the 
package insert and to enter this interventional study.
8.
Patients must be able to read and understand English.
3.3.5
Patient Exclusion Criteria
For enrollment into the study, patients will be excluded if they fall under any of the 
following exclusion criteria.
Table 3.3.5-1
Exclusion Criteria
1.
Any patient who participated in another clinical trial within 30 days of enrollment into the current 
study.
2.
Females who are breast-feeding and/or who are pregnant at the time of study enrollment, or who 
plan to become pregnant during the study.
3.
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3.4
Outcome Variables
3.4.1
Primary Endpoint (Main Study)
The primary endpoint is the difference in the proportion of patients with all-cause 
hospitalizations for patients using Abilify MyCite versus virtual matched controls from 
baseline to Day 180.
3.4.2
Secondary Endpoints (Main Study)
The secondary endpoint is the difference between groups (Abilify MyCite versus virtual 
matched controls) in the proportion of patients with at least 80% proportion of days 
covered (PDC) (with antipsychotic medication) from baseline to Day 180.
3.4.3
Exploratory Endpoints (Main Study)
 
 
 
 
 
 
 
 
 
 
).
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3.4.4
Endpoints for the Exploratory Study
For the exploratory study, as applicable, endpoints described in Section 3.4.1, 
Section 3.4.2, and Section 3.4.3 will be assessed for Sequence 1 vs Sequence 2 as a 
post-hoc analysis. Results from the exploratory study will be analyzed separately from 
the main study results.
3.5
Study Procedures
3.5.1
Main Study: Schedule of Assessments
Study assessment time points for enrolled patients are summarized for the main study in
Table 3.5.1-1.
Procedures for enrolling patients into the study are described in Section 3.5.1.2. 
 
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Table 3.5.1-1
Main Study: Schedule of Assessments (for Patients Enrolled at Sites)
Screeninga
Interventional Phaseb
Mid-study 
(or End-of-study) 
Visitc,d
Optional 2nd 
Abilify MyCite 
Treatmentd
End-of-
study
Visite
 
 
≤13 daysa
Baseline 
(Day 1)a
Day 30±7
Day 60±7
Day 90±7
Day 180±7
Days 180-≤360
Day 
≤360±7
Days 1- 360
Study site visit
X
X
X
Xe
Informed consent
X
Inclusion/exclusion 
criteria assessment
X
Smartphone and data 
plan verification 
X
Demographic 
information and 
medical / psychiatric 
history
X
Height and weight
measured
X
Vital signs
X
Onsite onboarding with
Abilify MyCite; patient 
pairs and applies patch
X
Dispense patches, 
aripiprazole + IEM, and 
other supplies
X
X
Physician reviews
Abilify MyCite 
dashboard data every 
2 weeksf
-----xf----
-----xf----
-----xf----
----------xf---------
--------xf-------
-----xf---
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Table 3.5.1-1
Main Study: Schedule of Assessments (for Patients Enrolled at Sites)
Screeninga
Interventional Phaseb
Mid-study 
(or End-of-study) 
Visitc,d
Optional 2nd 
Abilify MyCite 
Treatmentd
End-of-
study
Visite
 
 
≤13 daysa
Baseline 
(Day 1)a
Day 30±7
Day 60±7
Day 90±7
Day 180±7
Days 180-≤360
Day 
≤360±7
Days 1- 360
 
 
 
 
 
Concomitant 
medications
Xh
Hospitalizations (all-
cause and psychiatric)
Xh
 
aThe screening and baseline visits can be combined. 
bThe interventional period begins with the baseline visit and ends at the Day 180 visit (or early termination [ET] if the patient withdraws or is withdrawn from 
the study prematurely). Clinical data will be collected as part of routine clinical practice, not as a requirement for the protocol.
cAll patients will complete the Day 180 visit. If a patient withdraws or is withdrawn from the study prematurely (eg, before completing the scheduled Day 180
visit), then an early ET visit should be performed, at which time all assessments and procedures that were to have been performed at the Day 180 visit 
should be completed. In such cases, the reason for the ET must be recorded.
dAt the Day 180 visit, a second, optional interventional period (up to 6 months of Abilify MyCite; Days 180-≤360) may be initiated per the joint decision of 
the patients with their study physician. If the patient is not continuing in the optional second Abilify MyCite treatment period (Days 180-≤360), then the 
Day 180 visit is the final visit. Patients need to be on aripiprazole to use the system for the optional second treatment period.
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eThe Day 360 visit (and activities) are only completed for patients in the optional second Abilify MyCite treatment period (Days 180-≤360). If a patient 
withdraws or is withdrawn from the study prematurely (eg, before completing the scheduled Day 360 visit), then an early ET visit should be performed, at 
which time all assessments and procedures that were to have been performed at the Day 360 visit should be completed. In such cases, the reason for the ET 
must be recorded.
fThe study 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.
gIf a patient does not have a routine care visit at Day 30, Day 60, or Day 90, the scale will be administered by phone.
hData collected if available per routine clinical practice 
 at completion of the study (plus 3 months to allow for 
lag in 
 patient data from baseline through end of study will be included.
 
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3.5.1.1
 
 
 
 
 
Data will also be collected from a virtual matched control group, as described in 
Section 3.5.4. 
3.5.1.2
Main Study: Enrollment Procedures
The study physician will make the decision regarding the patient’s suitability for the 
study. The determination that a patient is appropriate for treatment with aripiprazole 
(regardless of whether or not they would switch from current treatment) and initiation of 
Abilify MyCite will be made prior to and independent of study initiation. Following the 
treating physician’s determination of eligibility, patients will be approached for 
enrollment. As part of their routine office visits, patients will be approached for potential 
enrollment into the study by their treating physician.
3.5.1.3
Main Study: Screening
Eligibility assessment per the treating physician’s decision and informed consent will be 
conducted during a screening visit up to 13 days prior to and including the baseline visit.
For patients enrolling into the study, those not on aripiprazole at screening will use the 
screening period for conversion to aripiprazole from other antipsychotics according to the 
approved labels.
3.5.1.4
Main Study: Baseline
The baseline visit marks the beginning of the interventional phase. Patients will receive 
training and onboarding with Abilify MyCite as outlined in Table 3.5.1-1. Training will 
be based on the commercial training materials for Abilify MyCite to reflect real-world 
practice. Baseline assessments will include: demographic data, medical and psychiatric 
history, height, weight, vital signs, and hospitalization history (all-cause and psychiatric). 
3.5.1.5
Main Study: Treatments
Patients will initiate Abilify MyCite upon study enrollment (at the baseline visit) and will 
continue use through Day 90 (with an optional second use period over Days 180-≤360),
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as deemed clinically appropriate by their treating physician. Abilify MyCite may be 
started and stopped as clinically appropriate based on physician judgment. Ability 
MyCite metrics will be captured throughout use.
During periods of nonuse of Abilify MyCite, the patient continues with oral aripiprazole 
or other appropriate treatment, per routine clinical care.
3.5.1.6
Main Study: Interventional Phase (Day 1 to Day 180)
After the baseline visit, there are no mandated visits until Day 180. However, it is 
anticipated that patients will undergo medical evaluation at regular intervals. Data 
collected at these routine care visits, such as Abilify MyCite use changes and AEs (as 
described in Section 4), will be entered into the study database. Physicians are expected
to regularly review the Abilify MyCite dashboard data during active Abilify MyCite use 
as consistent with routine care, approximately every 2 weeks.
At the time points indicated in Table 3.5.1-1, the patient, caregiver (if applicable), and 
physician outcomes scales will be completed.
3.5.1.7
Main Study: Day 180 Mid-study (or End-of-study) Visit
The Day 180 visit marks the end of the interventional phase. All patients will complete 
the Day 180 visit. Data collected at the Day 180 visit, such as Abilify MyCite use 
changes and certain AEs (as described in Section 4), will be entered into the study 
database. 
At the Day 180 visit, a second, optional interventional period (up to 6 months of Abilify 
MyCite; Days 180-≤360) may be initiated per the joint decision of the patients with their 
study physician; if the patient is not continuing into the optional period, then the Day 180 
visit is the final visit. During this second, optional interventional period, patients may 
start and stop Abilify MyCite as clinically indicated.
If a patient withdraws or is withdrawn from the study prematurely (eg, before completing 
the scheduled Day 180 visit), then an early ET visit should be performed, at which time 
all assessments and procedures that were to have been performed at the Day 180 visit 
should be completed. In such cases, the reason for the ET must be recorded. 
3.5.1.8
Main Study: Second Interventional Period (Day 180 to Day 360)
At the Day 180 visit (or later during the Day 180-<360 period), patients will decide 
jointly with their study physician whether to restart Abilify MyCite for a second 
interventional period (Days 180-≤360). Patients will re-initiate Abilify MyCite at 
Day 180 (or later during the Day 180-<360 period) and the second interventional period 
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will proceed similarly to the interventional period described in Section 3.5.1.6. Data 
collected at routine care visits between Day 180 and Day 360, such as Abilify MyCite use 
changes and AEs (as described in Section 4), will be entered into the study database. 
Physicians are 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 patients need to be on aripiprazole to use the system for the optional second 
treatment period.
 
If a patient withdraws or is withdrawn from the study prematurely (eg, before completing 
the scheduled Day 360 visit), then an early ET visit should be performed, at which time 
all assessments and procedures that were to have been performed at the Day 360 visit 
should be completed. In such cases, the reason for the ET must be recorded.
3.5.1.9
 
 
 
 
Additional patient data will be collected if available per routine clinical practice, eg, prior 
(up to 12 months) hospitalizations (all-cause and psychiatric) and concomitant 
medications.
3.5.2
Exploratory Study: Schedule of Assessments
Study assessment time points for enrolled patients are summarized for the exploratory 
study in Table 3.5.2-1. 
Procedures for the exploratory study will be similar to those in the main study 
(Section 3.5.1.1 through Section 3.5.1.5, and Section 3.5.1.9), with the exception that 
there will be 1-month intervals of Abilify MyCite use (and 1-month intervals of 
prohibition of Abilify MyCite use), as diagrammed in the study schematic (Figure 3.1-3). 
During periods of nonuse of Abilify MyCite, the patient continues with oral aripiprazole, 
per routine clinical care. If the patient goes on another (non-aripiprazole) treatment, data 
will be collected, but the patient will not return to Abilify MyCite if that treatment is not 
appropriate.
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For the exploratory study, the site visits will be at screening, baseline (which may be the 
same day as the screening visit), Day 180, and Day 360; additional visits are to occur as
clinically indicated, and assessments will occur at the times indicated in Table 3.5.2-1. 


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Table 3.5.2-1
Exploratory Study: Schedule of Assessments (for Patients Enrolled at Sites)
Screeninga
Interventional Phaseb
End-of-
study Visitc
 
≤13 daysa
Baseline 
(Day 1)a
Day 30±7
Day 60±7
Day 180±7
Day 300±7
Day 360±7
Days 1- 360
Study site visit
X
X
X
X
Informed consent
X
Inclusion/exclusion criteria 
assessment
X
Smartphone and data plan 
verification 
X
Demographic information and 
medical / psychiatric history
X
Height and weight measured
X
Vital signs
X
Onsite onboarding with Abilify 
MyCite; patient pairs and applies 
patch
X
Dispense patches, aripiprazole + 
IEM, and other suppliesd
X
-----x----
-----x----
-----x----
-----x----
-----x----
Physician reviews Abilify MyCite 
dashboard data every 2 weekse
-----x----
-----x----
-----x----
-----x----
-----x----
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 3.5.2-1
Exploratory Study: Schedule of Assessments (for Patients Enrolled at Sites)
Screeninga
Interventional Phaseb
End-of-
study Visitc
 
≤13 daysa
Baseline 
(Day 1)a
Day 30±7
Day 60±7
Day 180±7
Day 300±7
Day 360±7
Days 1- 360
Concomitant medications
Xg
Hospitalizations (all-cause and 
psychiatric)
Xg
 
Seq = Sequence.
aThe screening and baseline visits can be combined. 
bThe interventional period begins with the baseline visit and ends at the Day 360 visit (or ET if the patient withdraws or is withdrawn from the study 
prematurely). Clinical data will be collected as part of routine clinical practice, not as a requirement for the protocol.
cAll patients will complete the Day 360 visit. If a patient withdraws or is withdrawn from the study prematurely (eg, before completing the scheduled Day 360
visit), then an early ET visit should be performed, at which time all assessments and procedures that were to have been performed at the Day 360 visit 
should be completed. In such cases, the reason for the ET must be recorded.
dThe physician will dispense Abilify MyCite supplies (patches, aripiprazole + IEM, and other supplies) during routine visits as required during the study per 
Sequences 1 and 2. Note that “----x----” indicates the activity can occur multiple times during the period.
eThe study 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 that the activity will occur multiple times during the period.
fIf a patient does not have a routine care visit at the given visit, the scale will be administered by phone.
gData collected will be collected 
 at completion of the study (plus 3 months to allow for lag in 
 
 patient data from baseline through end of study will be included. CCI
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3.5.3
Assessments (Main and Exploratory Studies)
3.5.3.1
Adverse Events
Refer to Section 4 (Reporting of Adverse Events).
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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3.5.4
Virtual Matched Control Group (Main Study Only)
 
 
 
 
 
 
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The virtual matched control group is not applicable for the exploratory study.
3.5.5
End of Study
The End of Study Date is defined as the last Date of Contact or the Date of Final Contact 
Attempt for the last patient completing or withdrawing from the study, plus a 3-month lag 
time to allow for 
The End of Study Date will be the last date overall (main study or exploratory study). 
3.6
Stopping Rules, Withdrawal Criteria, and Procedures
3.6.1
Entire Study
Otsuka and/or the IRB/IEC reserve the right to terminate the study at any time. In this 
event, all data collection will end. After the collected data is received, study physicians 
will be compensated as contractually agreed. If Otsuka terminates or suspends the study 
for safety or unanticipated other reasons, prompt notification will be given to study sites, 
IRBs/IECs, and regulatory authorities in accordance with regulatory requirements.
3.6.2
Individual Site
The IRB/IEC reserves the right to terminate participation of individual study sites at any 
time. Individual study sites may also be terminated for cause by Otsuka per contractual 
agreement. In such cases, all data collection at terminated study sites will end. After the 
collected data is received, the study physicians will be compensated as contractually 
agreed.
The sponsor should be notified promptly if the study is terminated by the physician or the 
IBR/EC at the site. 
3.6.3
Individual Patient
Patient withdrawal from the study will be based upon physician clinical determination 
and/or patient decision. Participation in the study is voluntary, and all patients are free to 
terminate their participation at any time. In the event of study withdrawal, the study 
physician will record the reason for study withdrawal and continue to follow-up with the 
patient for any unresolved SAEs. Upon patient withdrawal from the study, all data
collection will end, but all study data collected up to withdrawal will be included in the 
study database.
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In addition, patients falling under the following criteria must be withdrawn from the 
study:

occurrence of any intercurrent illness or abnormality in a laboratory assessment 
which, in the opinion of the physician, warrants the patient’s permanent withdrawal 
from the study;

at the request of the patient or physician;

patient becomes pregnant; or

patient is lost to follow-up.
3.6.4
 
3.7
Protocol Deviations
As this is a real-world study, the chances of protocol deviations occurring in this study 
are minimal and limited to data breaches, deviations to Good Clinical Practice, or 
treatment outside of the parameters of the Abilify MyCite US package insert.
In the event of a significant deviation from the protocol due to an emergency, accident, or 
mistake (eg, violation of informed consent process or patient enrolled in violation of 
eligibility criteria), the study physician will notify HealthCore, who will contact the 
sponsor at the earliest possible time by telephone. The study physician and sponsor will 
come as quickly as possible to a joint decision regarding the patient’s continuation in the 
study. This decision will be documented by the study physician and the sponsor.
4
Reporting of Adverse Events
In this phase 4 study, all SAEs (ie, drug-related SAEs and device-related SAEs), 
device-related nonserious AEs (ie, related to the device component of Abilify MyCite 
treatment, including those leading to withdrawal from Abilify MyCite), potential 
hepatotoxicity cases, and pregnancies will be monitored and collected. For device-related 
AEs leading to withdrawal from Abilify MyCite, the reason for withdrawal will be 
collected.
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4.1
Definitions
4.1.1
Drug-related Serious Adverse Events
A serious adverse event (SAE) includes any event that results in any of the following 
outcomes:

Death

Life-threatening; eg, the patient was, in the opinion of the HCP, 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.

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 (eg, 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 patient 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.
4.1.2
Device-related Serious Adverse Events
A device-related SAE is defined as:

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;

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
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:

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 study, device-related SAEs include any event that is related to the 
IEM, patch, or the phone and application (reported to Otsuka).
4.1.3
Nonserious Adverse Events 
Nonserious AEs are all AEs that do not meet the criteria for a "serious" AE (Section 4.1.1
and Section 4.1.2). As described above, only nonserious AEs that are related to the device 
(ie, related to the device component of Abilify MyCite, including those leading to 
withdrawal from Abilify MyCite) will be collected in this study.
4.1.4
Immediately Reportable Event
Immediately reportable events (IREs) include the events discussed in Section 4.1.1, 
Section 4.1.2, and any of the following outcomes:

Any SAEs;

Any AEs related to occupational exposure;

Any device-related nonserious AEs, including skin irritation that is Grade 2 or worse 
(see Appendix 9), ie, definite erythema that is readily visible; minimal (or worse) 
edema or minimal (or worse) papular response;

Potential drug-induced liver injury (DILI) case (see Section 4.4);

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 as an AE in the data collection tool,
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If a patch-related nonserious AE occurs, the skin irritation scale should be completed; 
Grade 2 or above on the scale are considered medically significant for purposes of 
reporting.  
4.1.5
Abnormal Clinical Laboratory Test Changes
Clinical laboratory assessments will be conducted at the HCPs’ discretion to ensure 
safety of the patient. Ongoing clinical laboratory assessments are not required for this 
study. 
In the event that the HCP orders a laboratory test in the interest of patient safety, it is the 
HCP’s responsibility to review the results of all laboratory tests as they become available. 
Abnormal laboratory tests that a physician deems related to the product would be 
considered a SAE and/or IRE if they fit the criteria set forth in Section 4.1.1, 
Section 4.1.2, and Section 4.1.4.
4.1.6
Severity
Adverse events will be graded on a 3-point scale and reported as indicated in the data 
collection tool. 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.
4.1.7
Abilify MyCite Causality
Assessment of causal relationship of an SAE or device-related nonserious 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 SAE or 
device-related nonserious AE.
Not Related:
There is no temporal or causal relationship between Abilify 
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4.2
Eliciting and Reporting Serious Adverse Events
The HCP will assess patients for the occurrence of SAEs. To avoid bias in eliciting 
SAEs, patients should be asked the non-leading question: “How have you felt since your 
last visit?” All SAEs reported by the patient must be recorded on the source documents 
and data collection tool provided by the sponsor. Serious AE collection is to begin after a 
patient has signed the ICF. All SAEs will be collected starting from the signing of the 
ICF until the end of the study.
Use medical terminology in SAE reporting. Serious 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 SAE 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. An SAE that 
undergoes a change in severity, seriousness, or toxicity should be reported as a new SAE.
In addition, Clinical Safety and Pharmacovigilance must be notified immediately by 
telephone, fax, or e-mail of any IREs according to the procedure outlined below, in 
Section 4.3. Special attention should be paid to recording hospitalization and concomitant 
medications.
4.3
Immediately Reportable Events 
The HCP must immediately report after becoming aware of any SAE, potential DILI, 
confirmed pregnancy, or any device-related nonserious AEs (which include skin irritation 
that is Grade 2 or worse per Appendix 9, ie, definite erythema that is readily visible; 
minimal [or worse] edema or minimal [or worse] papular response) by telephone, fax, or 
e-mail to Clinical Safety and Pharmacovigilance using the contact information on the 
cover page of this protocol (see also Appendix 2). An IRE form must be completed and 
sent by e-mail, fax, or overnight courier to Clinical Safety and Pharmacovigilance. 
Patients 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 HCP will provide or arrange appropriate supportive care 
for the patient and will provide prompt updates on the patient’s status to Clinical Safety 
and Pharmacovigilance.
4.4
Potential Drug-induced Liver Injury
For a patient who receives laboratory tests, if the test indicates an elevation in aspartate 
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(ULN), a total bilirubin level should also be evaluated. If the total bilirubin is 2 times 
the ULN, an IRE form for be completed, with all values listed.
4.5
Pregnancy
Females of childbearing potential (FOCBP) are defined as female patients or female 
partners of the male patients for whom menstruation has started and who are not 
documented as sterile (eg, have had a bilateral oophorectomy and/or hysterectomy or 
who have been postmenopausal for at least 12 months).
Before study enrollment, FOCBP must be advised of the importance of avoiding 
pregnancy during study participation and the potential risk factors for an unintentional 
pregnancy. The patient must sign an ICF stating that the risks and consequences were 
discussed with her.
During the study, all FOCBP should be instructed to contact the HCP immediately if they 
suspect they might be pregnant (eg, missed or late menstrual cycle).
If a female patient is suspected to be pregnant before the patient receives Abilify MyCite, 
the investigator can recommend the patient undergo a pregnancy test with their general 
practitioner or primary care physician. If the pregnancy is confirmed, the patient must not 
receive Abilify MyCite and must not be enrolled in the study. If pregnancy is suspected 
while the patient is taking Abilify MyCite, Abilify MyCite may be continued at HCP 
discretion until the result of the pregnancy test is known. If pregnancy is confirmed, 
Abilify MyCite may be continued at HCP discretion based on treatment guidelines for the 
medication administered. If the HCP discontinues the patient from Abilify MyCite, it 
must be performed in an appropriate manner (eg, dose tapering if necessary for patient
safety) and the patient will be withdrawn from the study. (Exceptions to study
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 HCP must immediately notify the sponsor of any pregnancy associated with Abilify 
MyCite exposure during the study and for 30 days for a female patient, 90 days for 
female partner of a male patient, after the last dose of Abilify MyCite, and record the 
event on the IRE form and forward it to the sponsor. Pregnancies of patients or their 
partners will be followed to term. In the event of pregnancy of a patient’s partner, consent 
to follow the pregnancy will be obtained. The sponsor will forward Pregnancy 
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Protocol-required procedures for study discontinuation and follow-up must be performed 
on the patient unless contraindicated by pregnancy (eg, x-ray studies). Other appropriate 
pregnancy follow-up procedures should be considered, if indicated. In addition, the HCP 
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. 
4.6
Follow-up of Serious Adverse Events
Serious AEs that are identified or ongoing at the last scheduled contact must be 
recorded in the data collection tool and reported to the Clinical Safety and 
Pharmacovigilance department according to the reporting procedures outlined in 
Section 4.3. This may include unresolved previously reported SAEs, or new SAEs. 
The HCP will follow SAEs until the events are resolved, stabilized, or the patient is lost 
to follow-up. Resolution means that the patient has returned to the baseline state of health 
and stabilized means that the HCP does not expect any further improvement or worsening 
of the patient’s condition. The HCP will continue to report any significant follow-up 
information to Clinical Safety and Pharmacovigilance up to the point the event has been 
resolved.
4.6.1
Follow-up and Reporting of Serious Adverse Events Occurring 
after Last Scheduled Contact
Any new SAEs reported by the patient to the HCP that occur after the last scheduled 
contact, and are determined by the HCP to be reasonably associated with the use of 
Abilify MyCite, should be reported to Otsuka Pharmaceutical Development and 
Commercialization, Inc (OPDC). 
This may include SAEs that are captured on follow-up telephone contact or at any other 
time point after the defined study period (eg, up to last scheduled contact). The HCP 
should follow SAEs identified after the last scheduled contact until the events are 
resolved, stabilized, or the patient is lost to follow-up. The HCP should continue to report 
any significant follow-up information to OPDC up to the point the event has been 
resolved or stabilized.
5
Data Collection
5.1
Data Sources
Data sources for this study include demographic and clinical data collected prospectively 
by study sites, data collected from Abilify MyCite, 
 
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 In order to maintain patient confidentiality, 
each patient will be assigned a unique study-specific patient ID upon study enrollment to 
use in place of the patient name or any other identifying information (eg, medical record 
number). Data collected from Abilify MyCite will be transferred to HealthCore and 
integrated with prospectively collected study data, 
 will be 
leveraged for analysis.
For data through the electronic case report forms (eCRFs), the study physician has the 
ultimate responsibility for the collection and reporting of all clinical and patient data and 
ensuring that the data are accurate and complete.
5.2
Electronic Case Report Forms and Electronic Data Collection
All clinical study data will be collected at the physician office or over the phone and 
entered into eCRF by trained site study personnel through a fully validated, 21 Code of 
Federal Regulations 11 and Health Insurance Portability and Accountability Act 
(HIPAA)-compliant EDC system. 
All study personnel involved in data entry will be trained on patient confidentiality and 
the EDC system prior to beginning data entry. Site users will be provided eCRF 
Completion Guidelines to assist with study data collection and entry. Study personnel 
will access the EDC system through a secure study website.
6
Quality Control and Quality Assurance
6.1
Monitoring
The sponsor has ethical, legal, and scientific obligations to follow this study in an orderly 
manner in accordance with pragmatic research principles, applicable regulatory 
requirements, and local laws. 
6.2
Auditing/Inspections
This study may be subject to audits or evaluations by regulatory authorities or Otsuka (or 
its designee). To enable such evaluations and/or audits, the study physician must agree to 
maintain and allow reasonable access to required patient and study records. The study 
physician agrees to keep the identity of all participating patients (sufficient information to 
link records, eg, hospital records), all original signed ICFs, SAE Forms, source 
documents, detailed records of treatment disposition, and adequate documentation of 
relevant correspondence (eg, letters, meeting minutes, telephone calls, reports). 
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Regulatory requirements for the archival of records for this study necessitate that 
participating physicians maintain detailed clinical data for a period of 3 years after the 
end of this study.
7
Statistical Methods and Planned Analyses
Complete details of the planned statistical analysis will be presented in the statistical 
analysis plan (SAP).
7.1
Sample Size
The primary endpoint for the study is the proportion of patients with at least 1 all-cause 
hospitalization from study start date to Day 180. The assumptions for the sample size 
calculation were based on input from 
 for patients diagnosed 
with SCH, BP1, or MDD who had at least 1 all-cause hospitalization or partial 
psychiatric hospitalization within the 60 days prior to enrollment. A control group event 
rate of 36.3% was estimated, weighted based on an expected study distribution of 25% 
patients with SCH, 25% with BP1, and 50% with MDD. Sample size calculations were 
based on testing 2 proportions using the Z-test with unpooled variance. The study sample 
size of 447 patients was calculated based on the following assumptions, informed from 
 20% reduction in the proportion of patients with all-cause hospitalizations in 
the Abilify MyCite group versus the virtual matched control group (29.04% Abilify 
MyCite versus 36.30% virtual matched control), 1:3 (Abilify MyCite : virtual matched 
controls) matching, 80% power, and maintaining an overall alpha level of 0.05 with the 
level of significance in a superiority hypothesis of 0.025. Sample size calculations will be 
documented in the SAP. Using a 30% dropout rate at 6 months, a sample size of 
640 patients will need to be enrolled to ensure completion of 447 patients. 
A virtual control group of approximately 1350 patients will be identified from the 
 
and matched to the final sample of Abilify MyCite patients. This will create 3 controls for 
every 1 Abilify MyCite patient, which reduces the required Abilify MyCite sample size 
as compared to a 1:1 match while maintaining statistical power. Controls will be matched 
to Abilify MyCite patients using a propensity score derived from 
 
 This process has been shown to minimize bias associated with sample selection. 
Further details on the matching process will be included in the SAP.
7.2
Analysis of Demographic and Baseline Characteristics
Demographic and baseline characteristics will be summarized for the study population 
overall and by treatment (Abilify MyCite versus virtual matched controls). Discrete 
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variables will be reported as count (frequency) and percent for each category. Continuous 
level variables (interval, ratio) will be reported as mean and standard deviation. Where 
applicable, range, minimum, maximum, and median will also be reported. Other 
statistics, measures of central tendency, and measures of dispersion may also be reported 
as outlined in the SAP.
It is likely that the virtual matched controls will lack some variables that are available to 
the Abilify MyCite sample. As a result, a comprehensive list of each variable in the 
Abilify MyCite sample will be listed, while "N/A" will be listed for each variable that is 
not available in the virtual matched control cohort. Balance in baseline characteristics 
across the 2 cohorts will be evaluated prior to analysis.
The details of this analysis will be fully described in the SAP.
7.3
Effectiveness Analyses
Effectiveness analysis for this study refers to the difference in the study endpoints within 
the Abilify MyCite cohort and the virtual matched controls. This analysis is further 
outlined in the primary endpoint and secondary endpoints sections (Section 7.3.1 and 
Section 7.3.2). A summary table will be presented reporting the difference between 
cohorts at Day 180. Potential adjustment for baseline values or differences that exist in 
the samples will be further outlined in the SAP.
7.3.1
Primary Endpoint
The primary endpoint compares the proportion of patients with all-cause hospitalizations 
between the Abilify MyCite and virtual matched control cohorts. The primary endpoint 
analysis will be a test of independent proportions. Standard methods for these analysis 
methods were developed by Fleiss and others15 and included in all statistical software 
systems. 
These tests are directional in nature since the alternative hypothesis is that the proportions 
in the Abilify MyCite cohort will be lower than the proportions in the virtual controls. 
Adjustments will be made to the alpha level to account for the one-tail nature of the 
alternative hypothesis (HA).

H0: P1 – P2 ≥ 0 versus HA: P1 – P2 < 0
Where:

P1 = proportion of Abilify MyCite patients with all-cause hospitalization from study 
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
P2 = proportion of virtual control patients with all-cause hospitalization from study 
start date to Day 180
7.3.2
Secondary Endpoint
The secondary endpoint compares the difference between groups (Abilify MyCite versus 
virtual matched controls) in the proportion of patients with at least 80% PDC (with
antipsychotic medication) from baseline to Day 180. 
This analysis will be a test of independent proportions between the Abilify MyCite and 
virtual matched control groups. 
7.3.3
Exploratory Endpoints
Details for the analysis of all exploratory endpoints (see Section 3.4.3 and Section 3.4.4) 
will be outlined in the SAP. It is understood that the list of variables might not be 
inclusive at this point and that alterations to these variables may be performed.
7.4
Safety Analyses
All safety summaries will be descriptive in nature. A detailed description of the 
summaries for the safety exploratory endpoint (see Section 3.4.3 [main study] and 
Section 3.4.4 [exploratory study]) will be described in the SAP.
7.5
Other Analyses
There are no plans to include any other analysis other than what has been described 
above. Any post-hoc testing that might arise from the results or findings will be discussed 
and conducted in accordance with standard and accepted statistical procedures.
7.6
Source Documents
Source documents are defined as the results of original observations and activities of a 
clinical investigation. Source documents may include, but are not limited to progress 
notes, electronic data, and recorded data from automated instruments. In this pragmatic 
trial, source documents will reside in the patient’s medical record. All source documents 
pertaining to this study will be maintained by the study physicians and made available for 
direct inspection by authorized persons. Study physicians will permit study-related 
monitoring, audits, IRB/IEC review, and regulatory inspection(s) by providing direct 
access to source data/documents by authorized persons as defined in the ICF.


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7.7
Data Collection
See Section 5 for study procedures relating to data collection. 
7.8
File Management and Records Retention at the Study Site
In this pragmatic trial, the majority of study documents will be site medical records. 
Regulatory requirements for the archival of records for this study necessitate that 
participating physicians maintain detailed clinical data for a period of 3 years after the 
end of this study. The study physician will take measures to prevent accidental or 
premature destruction of these documents.
Record retention at the study site is also addressed in Section 6.2.
8
Ethics and Responsibility
All study activities will be conducted in accordance with regulatory guidelines for 
real-world, pragmatic research. Study personnel at physician sites will be provided 
training on the study protocol, the ICF, data collection, and data entry to ensure both the 
protection of potential study patients as well as the scientific integrity of the study. Sites 
will be monitored remotely, with onsite monitoring employed only for cause.
8.1
Institutional Review Board / Independent Ethics Committee
The study physician must obtain prospective approval of the study protocol, ICF, and any 
patient information or recruiting materials, if applicable, prior to commencement of any 
study activities. All changes in research activity and all unanticipated problems involving 
risk to human patients or others must be reported promptly to the IRB/IEC.
The study physician will obtain continued review of the study at intervals not to exceed 
one year or otherwise specified by the IRB/IEC.
9
Confidentiality
All information generated in this study will be considered highly confidential and will not 
be disclosed to anyone not directly concerned with the study without the sponsor’s prior 
written permission. However, authorized regulatory officials and sponsor personnel (or 
their representatives) will be allowed full access to inspect and copy the records. All 
drugs, patient 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.


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Patients will be identified only by initials and unique patient numbers in eCRFs. Their 
full names may, however, be made known to a regulatory agency or other authorized 
officials if necessary.
9.1
Publication of Study Results
All information related to this study is considered confidential information belonging to 
Otsuka Pharmaceutical Development & Commercialization, Inc. and HealthCore as 
consistent with contractual agreement. A final study report will be generated following 
completion of data collection and analysis. Results and findings will be submitted to 
conferences and for publication in peer-reviewed scientific journals with authorship 
following the International Committee of Medical Journal Editors guidelines.
10
Amendment Policy
The study physician will not make any changes to this protocol without the sponsor’s 
prior written consent and subsequent approval by the IRB/IEC. Any permanent change to 
the protocol, whether it be an overall change or a change for specific study site(s), must 
be handled as a protocol amendment written by the sponsor or its designee. In the case of 
a protocol amendment, the study physician must sign the revised protocol and the 
amendment will be submitted to the IRB/IEC and approval prior to implementation of 
any changes specified in the protocol amendment.
When the IRB/IEC, study physicians, and/or the sponsor conclude that the protocol 
amendment substantially alters the study design and/or increases the potential risk to the 
patient, the ICF must be revised and submitted to the IRB/IEC for review and approval 
prior to implementation. The revised ICF must then be used to obtain consent from new 
patients entering the study as well as from currently enrolled patients if they are affected 
by the amendment, per IRB/IEC guidance.
11
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
 A formative usability study of the Otsuka MIND1 prototype by 
subjects with bipolar disorder or major depressive disorder. Otsuka Clinical Study 
Report for Protocol 316-13-204, issued 28 Jul 2014.
PPD


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4
 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 Report for Protocol 316-13-215, issued 18 Nov 2016.
5
 Phase 1, open-label trial to evaluate the skin irritation potential
and extent of adhesiveness of the RP4 patch following application to the skin of 
healthy, adult subjects. Otsuka Clinical Study Report for Protocol 316-13-205, issued 
26 Feb 2014.
6
 A multicenter, 8-week, open-label study to assess usability of the 
Medical Information Device #1 (MIND1) System in adult subjects with schizophrenia 
who are treated with oral aripiprazole. Otsuka Interim Synopsis Clinical Study Report 
for Protocol 316-14-220, issued 27 Feb 2015.
7
Data on file. Abilify MyCite. Human factors engineering/usability engineering report: 
HCP/caregiver interface. NDA 207202. Otsuka Pharmaceutical Development & 
Commercialization, Inc. 2015b.
8
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.
9
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 Rev 7. Issued 
22 Mar 2016.
14 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.
15 Fleiss JL. Statistical methods for rates and proportions. John Wiley & Sons; 1981.
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Appendices
Appendix 1
Names of Sponsor Personnel
Phone: 
E-mail: 
 
Phone: 
E-mail: 
 
Phone: 
 HealthCore
Phone: 
 or 
E-mail: 
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Appendix 2
Safety Reporting
For medical emergencies, the physician can contact the Global Safety and 
Pharmacovigilance department via a 24-hour telephone number: 
 A 
call to this telephone number does not alleviate the investigator’s responsibility to report 
an SAE in writing, via fax. 
Report Immediately Reportable Events (SAEs, potential DILI, confirmed pregnancies, 
and any device-related nonserious AEs [eg, skin irritation that is Grade 2 or worse per
Appendix 9]) to the Global Safety and Pharmacovigilance department as follows:
Global Safety and Pharmacovigilance
Fax: 
E-mail: 
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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 patients 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 patient for use. Each patch is designed 
for 7-day wear; extra devices are provided should the patients desire to 
change the patch more frequently during the period of familiarization 
or in case of sensor malfunction.
Computing Device & 
Accessories
Patients will use their own smartphone and required accessories. 
Patients 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 patient sleeps.
Abilify MyCite 
Reference Guide
A printed reference guide will provide explicit directions for normal 
use and troubleshooting.


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For you
For your patient
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Appendix 9
Skin Irritation Scoring System
Dermal Response:
Grade
Skin Event
0
No evidence of irritation
1
Minimal erythema, barely perceptible
2
Definite erythema, readily visible; minimal edema or minimal papular response
3
Erythema and papules
4
Definite edema
5
Erythema, edema, and papules
6
Vesicular eruption
7
Strong reaction spreading beyond the test site
Source: US Department of Health and Human Services, FDA Center for Drug Evaluation and Research, 
December 1999.


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Investigator Agreement
I have read the protocol, A Multicenter, 180-day Pragmatic Clinical Trial to Measure the 
Difference in All-cause Hospitalizations for Patients who are Using Abilify MyCite 
versus Virtual Matched Controls in Adults with Schizophrenia, Bipolar 1 Disorder, and 
Major Depressive Disorder and agree to ensure that all staff members involved in the 
conduct of this study are informed of their obligations in meeting the commitments in 
accordance with it.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described pragmatic trial.
________________________________________________
Signature and Date
________________________________________________
Print Name


Otsuka Pharmaceutical Development & Commercialization, Inc.
This page is a manifestation of an electronically captured signature
                                                                                                                                
SIGNATURE PAGE
Document Name:
Document Number:
Document Version:
Signed by
Meaning of Signature
Server Date
(dd-MMM-yyyy HH:mm ‘GMT’Z)
MIND1
316-13-217 Protocol
0001286660
2.0
Biostatistics Approval
08-Mar-2018 16:04 GMT+00
Clinical Approval
08-Mar-2018 16:25 GMT+00
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SAP_001.pdf: 
Protocol 316-13-217 
Confidential - Proprietary Information 
Protocol number: 316-13-217
Document title: A Multicenter, 180-day Pragmatic Clinical Trial to 
Measure the Difference in All-cause Hospitalizations for Patients 
Who Are Using Abilify MyCite Versus Virtual Matched Controls in 
Adults With Schizophrenia, Bipolar 1 Disorder, and Major 
Depressive Disorder  
Version number: 3.0 
Date of the document: 11 October 2019
NCT number:    NCT03643159 


Statistical Analysis Plan for A Multicenter, 180-day Pragmatic Clinical Trial to 
Measure the Difference in All-cause Hospitalizations for Patients who are Using 
Abilify MyCite versus Virtual Matched Controls in Adults with Schizophrenia, 
Bipolar 1 Disorder, and Major Depressive Disorder
Protocol No. 316-13-217
Otsuka Pharmaceutical
Development & Commercialization, Inc.
Otsuka Pharmaceutical Development & Commercialization, Inc.
2440 Research Boulevard
Rockville, Maryland 20850
October 11, 2019
Version Final
This document and its contents are the property of Otsuka Pharmaceutical Development & 
Commercialization, Inc. and are confidential.  Unauthorized copying or use is prohibited


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TABLE OF CONTENTS
TABLE OF CONTENTS ..................................................................................................................2
List of Abbreviations .........................................................................................................................4
1.0
INTRODUCTION..................................................................................................................6
2.0
STUDY OBJECTIVES..........................................................................................................9
2.1
Primary Objective ..........................................................................................................................9
2.2
Secondary Objective.......................................................................................................................9
2.3
9
3.0
STUDY INVESTIGATIONAL PLAN.................................................................................9
3.1
Study Design Overview ..................................................................................................................9
3.2
Study Population and Sites..........................................................................................................10
3.3
Randomization..............................................................................................................................10
3.4
Virtual Matched Control Group.................................................................................................10
3.5
Evaluation Schedule and Definitions..........................................................................................12
3.5.1
Baseline......................................................................................................................................12
3.5.2
Interventional Period..................................................................................................................12
3.5.3
Mid-Study (or End of Study) visit (Day 180) ............................................................................13
3.5.4
Optional Second Interventional Period ......................................................................................13
3.5.5
End of Study (Day 360) .............................................................................................................13
3.5.6
Early Terminations.....................................................................................................................13
4.0
STATISTICAL METHODOLOGY...................................................................................14
4.1
General Considerations................................................................................................................14
4.2
Sample Size Estimation................................................................................................................14
4.3
Analysis of Demographic and Baseline Characteristics............................................................15
4.4
Primary Endpoint.........................................................................................................................15
4.5
Secondary Endpoint .....................................................................................................................15
4.6
16
4.1
Missing data ..................................................................................................................................16
4.2
Safety Analysis..............................................................................................................................16
4.3
Other Analysis ..............................................................................................................................16
5.0
STATISTICAL ANALYSES ..............................................................................................16
5.1
Study Populations.........................................................................................................................16
5.1.1
Enrolled Population....................................................................................................................16
5.1.2
Analysis Population ...................................................................................................................16
5.1.3
Safety Population .......................................................................................................................16
5.2
Efficacy Analysis...........................................................................................................................16
5.3
Safety Analysis..............................................................................................................................17
5.3.1
AEs.............................................................................................................................................17
5.3.2
SAEs...........................................................................................................................................17
5.3.3
Potential Hepatotoxicity Cases...................................................................................................17
5.3.4
Pregnancy...................................................................................................................................17
6.0
17
7.0
21
8.0
25
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9.0
27
10.0
 
.29
11.0
APPENDIX F: Coding tables..............................................................................................30
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List of Abbreviations
Abbreviation
Definition 
AE
Adverse event
BP1
Bipolar 1 disorder
BMI
Body mass index
CI
Confidence interval
ClinRO
Clinician reported outcomes
E&M
Evaluation and management
ET
Early termination
GLM
General Linear Model
GPI
Generic product identifier
HCP
Healthcare provider
HCPCS
Healthcare common procedure coding system
HR
Hazard Ratio
ICD-10-CM
International Classification of Diseases, Tenth Revision, Clinical Modification
LAIs
Long-acting injectable antipsychotics
LOS
Length of stay
MedDRA
Medical Dictionary for Regulatory Activities
MDD
Major depressive disorder
OR
Odds ratio
OV
Office visit
PCT
Pragmatic clinical trial
PDC
Proportion days covered
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PT
Preferred Term
SAE
Serious adverse event
SCH
Schizophrenia
SD
Standard deviation
SOC
System organ class
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1.0 INTRODUCTION
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 patient 
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.1 This finding is 
problematic due to the relationship 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.1,2
Currently available methods for monitoring adherence have limitations; as such, an unmet need 
exists for a simple, accurate solution for adherence monitoring to enable healthcare providers
(HCPs) to objectively measure whether a patient was adherent to treatment. Increasing HCP 
awareness of patient nonadherence and its role in suboptimal response may allow for better 
treatment decision making and allow an opportunity for more HCP/patient engagement in care. The 
available evidence suggests that patient engagement or activation in serious mental illness, while 
not a main focus in clinical practice, may provide substantial benefit to patient health outcomes, 
including management of comorbid conditions, and should be encouraged.
Abilify MyCite® (aripiprazole tablets with sensor) was developed to fulfill these unmet needs. The 
Abilify MyCite system is a drug-device combination product comprised of aripiprazole (an atypical 
antipsychotic) tablets embedded with an ingestible event marker (IEM) sensor that communicates 
with a patch (wearable sensor) and a medical software application with collected information 
(ingestion, mood, activity, rest) tracked and summarized for patients, HCPs, and potentially 
caregivers. Abilify MyCite is intended to track drug ingestion and is indicated for the treatment of 
adults with schizophrenia (SCH), bipolar 1 disorder (BP1) (acute treatment of manic and mixed 
episodes or maintenance treatment), and major depressive disorder (MDD) (adjunctive 
treatment).3Abilify MyCite can provide objective patient 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 patients to engage in taking a more 
active role in their personal wellbeing. The Abilify MyCite system and indications are summarized 
in Table 1-1.
                                                
1 Cramer JA, Rosenheck R. Compliance with 
medication regimens for mental and physical disorders. Psychiatry
Serv. 1998;49:196-201.
2 Proteus Digital Health Wearable Sensor Investigator's Brochure Rev 7. Issued 22 Mar 2016.
3 ABILIFY MYCITE (aripiprazole tablets with sensor) US Prescribing Informa
tion. Otsuka Pharmaceutical Co., 
Ltd., Tokyo, Japan, Proteus Digital Health, Inc., Redwood City, CA, and Otsuka America Pharmaceutical, Inc, 
Rockville MD; 2017.
  


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Table 1-1: Overview of the Abilify MyCite System
Characteristic
Description
Components

Aripiprazole tablet embedded with an IEM sensor (Abilify 
MyCite)

MyCite Patch (wearable sensor) that detects the signal from the 
IEM sensor after ingestion and transmits data to a smartphone

MyCite App (a smartphone application [app] which is used with 
a compatible smartphone to display information for the patient)

Web-based portal for HCPs 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 SCH; 
treatment of BP1 (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.
Limitations of use

The ability of Abilify MyCite to improve patient 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 has been tested in patients 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 patients and 


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HCPs/caregivers.4,5,6,7,8,9,10,11,12 The current pragmatic clinical trial (PCT) is designed to evaluate the 
impact of Abilify MyCite use on antipsychotic medication adherence, all-cause hospitalizations, 
healthcare resource utilization (HCRU), and patient-reported outcomes (PROs) in a community 
practice-based setting.
                                                
4 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.
5
 A formative usability study of the Otsuka MIND1 prototype by subjects with bipolar 
disorder or major depressive disorder. Otsuka Clinical Study Report
for Protocol 316
-13-204, issued 28 Jul 2014.
6
 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 Schizop
nia 
(SCH), Major Depressive Disorder (MDD), or Bipolar 1 Disorder (BP1) Who Are Treated With Oral Aripipraz
Otsuka Clinical Study Report for Protocol 316
-13-215, issued 18 Nov 2016.
7
 Phase 1, open
-label trial to evaluate the skin 
irritation potential and extent of adhesiveness 
of the RP4 patch following application to the skin of healthy, adult subjects. Otsuka Clinical Study Repo
Protocol 316
-13-205, issued 26 Feb 2014.
8
 A multicenter, 8
-week, open-label study to assess usability of the Medical Information 
Device #1 (MIND1) System in adult subjects with schizophrenia who are treated with oral aripiprazole. O
Interim Synopsis Clinical Study Report for Protocol 316
-14-220, issued 27 Feb 2015.
9 Data on file. Abilify MyCite. Human factors engineering/usability engineering report: HCP/caregiver inter
NDA 207202. Otsuka Pharmaceutical Development & Commercialization, Inc. 2015b.
10 Peters-Strickland T, Pestreich L, Hatch A, Rohatagi S, Baker RA, Doch
erty 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.
11 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.
12 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. Neuropsychi
Treat. 2017;13:2641-51.
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2.0 STUDY OBJECTIVES
2.1 Primary Objective
The primary objective of this study is to assess the difference in all-cause hospitalizations between 
patients using Abilify MyCite versus virtual matched controls at Day 180.
2.2 Secondary Objective
The secondary objective is to assess the difference in medication adherence, as measured by the 
proportion of patients with at least 80% proportion of days covered (PDC) with antipsychotic 
medication, between patients using Abilify MyCite versus virtual matched controls between 
baseline and Day 180.
2.3
 
 
 
 
3.0 STUDY INVESTIGATIONAL PLAN
3.1 Study Design Overview
This is a 180-day, phase 4, open-label, prospective, PCT to assess the difference between all-cause 
hospitalizations in patients using Abilify MyCite (for Months 1-3, then prohibited for Months 4-6) 
versus virtual matched controls. Virtual matched controls 
will be receiving treatment as usual (i.e., any product other than Abilify 
MyCite, which may be oral aripiprazole or any other product). An exploratory study with a 
different set of physician sites and patients is planned in conjunction with this study, however this 
document describes the analyses for the main study only.
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3.2 Study Population and Sites
The target population for this study consists of adult patients with SCH, BPI, or MDD, being 
treated with aripiprazole or for whom treatment with aripiprazole would be deemed appropriate by 
their treating physician, who have had at least one all-cause (including psychiatric) hospitalization 
or at least one psychiatric partial hospitalization within 60 days prior to study enrollment. Patient 
inclusion and exclusion criteria are outlined in sections 3.3.4 and 3.3.5 of the study protocol, 
respectively. Enrollment of a total of 640 patients is planned. To achieve balanced enrollment of the 
targeted diagnoses, a minimum enrollment of each diagnosis will be 25% or approximately 160 
patients.
Participation of approximately 80 US physician sites 
 
hat provide care for a high volume of patients in the target population 
is anticipated.
3.3 Randomization
Not applicable.
3.4 Virtual Matched Control Group
Enrolled patients will be matched to a virtual control group in a 1:3 ratio (enrolled patients on 
Abilify MyCite treatment : virtual matched controls).
 
 The 
matching process will be conducted after 6-month study data (or early termination data, if 
applicable) is collected for all Abilify MyCite patients. The virtual matched control group identified 
in this process will be used for all study analyses with a small amount of attrition expected for the 
12-month analyses for controls who no longer have Anthem insurance coverage.
A pool of potential controls will first be identified using the following criteria:

≥1 day of enrollment in an Anthem-affiliated commercial, Medicaid, or Medicare health 
plan with medical and pharmacy benefits during the observation period (from date of First 
Patient In up until date of Last Patient In)13.

≥1 pharmacy claim for any atypical antipsychotic (excluding Abilify MyCite, clozapine, and 
long-acting injectable antipsychotics [LAIs]14)15 during the observation period (Appendix F, 
Tables 2a and 2b).
                                                
13 Timeframe may 
be extended if additional sample is needed.
14 LAIs include: Aripiprazole monohydrate (Abilify Mantenna), Aripiprazole lauroxil (Aristada), Olanzapi
pamoate (Zyprexa Relprevv), Paliperidone palmitate (Invega Sustenna), Paliperidone palmitate (Invega Trinz
a), 
Risperidone microspheres (Risperdal Consta)
15 Drugs include: Aripiprazole, Asenapine
Maleate, Brexpiprazole, Cariprazine
HCl, , Iloperidone,  Paliperidone, 
PimavanserinTartrate,  Quetiapine
Fumarate, Risperidone,  Ziprasidone
HCl, Ziprasidone Mesylate
.
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
≥1 all-cause hospitalization or partial psychiatric hospitalization16 that occurs at most 60 
days prior to a pharmacy claim for any atypical antipsychotic (excluding Abilify MyCite, 
clozapine, and LAIs).
o
The earliest such pharmacy claim observed after the earliest observed hospitalization 
will be set as the initial (temporary) index date for each potential control.
o
For patients with ≥2 qualifying hospitalization/pharmacy claim episodes, an iterative 
process will be used to find the best match, and the final index date will be assigned 
accordingly.

Age 18 to 63 on index date.

≥1 claim for SCH, BP1, or MDD on or before index date.

No claims for pregnancy during the observation period.

No claims for any LAI during the observation period.

≥180 days of medical and pharmacy enrollment prior to index date

≥180 days of medical and pharmacy enrollment following index date
Prior to matching, the pool of potential controls and the Abilify MyCite cohort will be stratified by 
psychiatric diagnosis (SCH, BP1, MDD). The Abilify MyCite cohort psychiatric diagnosis will be 
based on the psychiatric diagnosis recorded in the eCRF. The potential controls psychiatric 
diagnosis will be based on the psychiatric diagnosis identified 
 In the event 
that more than one of the qualifying psychiatric diagnoses is identified 
, the following 
hierarchy will be applied to potential controls: SCH>BP1>MDD.
From this pool of patients, combined with the active arm, logistic regression will be used within 
each psychiatric diagnosis to estimate a propensity score for each patient, where propensity refers to 
a patient’s pre-index likelihood to be in the active arm. The dependent variable equals 1 for patients 
in the active arm and 0 for the controls. The following variables may be considered for inclusion in 
the propensity score model; a final determination will be made using descriptive study results on 
patient baseline characteristics.

Age

Gender

Month of index date

Plan type (commercial, Medicaid, or Medicare health plan with medical and pharmacy 
benefits)

Number of fills for any atypical antipsychotic over 6-12 months prior to index date

 

Occurrence/number of visits with a psychiatrist over 6-12 months prior to index date

Comorbidities over 6-12 months prior to index date
                                                
16 Defined as a medical claim with place of service code = 52 (“Psychiatric Facility
-Partial Hospitalization”), or 
with HCPCS codes H0035 or S0201.
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
Region of patient residence (Northeast, South, Midwest, West)
The estimated propensity scores will be used to match active arm patients to the virtual controls in a 
1:3 ratio. Prior to assessing outcomes, the validity of the propensity score adjustment will be 
assessed by (1) graphically examining the overlap in propensity scores across treatment and control 
groups17, and (2) comparing balance in all baseline characteristics across the cohorts via 
standardized mean differences. A standardized mean difference >10% in absolute value will be 
used to indicate potential imbalance that may warrant further investigation or adjustment (e.g. 
through regression analysis).18 Propensity score models will be finalized prior to the assessment of 
outcomes.
3.5 Evaluation Schedule and Definitions
Patients will be followed from baseline until Day 180. Following Day 180, a second optional 
interventional period from Day 180 to Day 360 may be initiated per the joint decision of the 
patients with their study physician.
3.5.1
Baseline
The baseline visit marks the beginning of the interventional phase. Patients will receive training and 
onboarding with Abilify MyCite based on the commercial training materials for Abilify MyCite to 
reflect real-world practice. Baseline assessments include: demographic data, medical and 
psychiatric history, height, weight, and corresponding calculated body mass index (BMI), vital 
signs, and hospitalization history (all-cause and psychiatric). 
 
 
For analysis, baseline includes assessments conducted and patient data collected at or prior to the 
baseline visit and before first use of Abilify MyCite.
3.5.2
Interventional Period
The interventional period is from baseline to Day 180. Patients will use Abilify MyCite from 
baseline through Day 90. Day 91 through Day 180 is an Abilify MyCite nonuse period during 
which patients will continue with oral aripiprazole or other appropriate treatment, per routine 
clinical care.
After the baseline visit, there are no mandated visits until Day 180. However, it is anticipated that 
patients will undergo medical evaluation at regular intervals. Data collected at these routine care 
visits include Abilify MyCite use changes and adverse events (AEs).
 
 
                                                
17 Garrido MM, Kelley AS, Paris J, Roza K, Meier DE, Morrison RS, Aldridge MD. Methods for constructing 
assessing propensity scores. Health services research. 2014 Oct 1;49(5):1701
-20
18 Austin PC. Optimal caliper widths for propensity
-score matching when
estimating differences in means and 
differences in proportions in observational studies. Pharm Stat. 2011 Mar
-Apr;10(2):150-61
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3.5.3
Mid-Study (or End of Study) visit (Day 180)
The Day 180 (± 7) visit marks the end of the interventional phase. All patients will complete the 
Day 180 visit. Data collected at the Day 180 visit includes Abilify MyCite use changes and AEs. 
At the Day 180 visit, a second, optional interventional period (up to 6 months of Abilify MyCite; 
Day 180 through up to Day 360) may be initiated per the joint decision of the patients with their
study physician; if the patient is not continuing into the optional second interventional period
(section 3.5.4), then the Day 180 visit is the final visit.
3.5.4
Optional Second Interventional Period
At the Day 180 visit (or later during the Day 180 through up to 360 period), patients will decide 
jointly with their study physician whether to restart Abilify MyCite for a second interventional 
period (Day 180 through up to 360). Patients will re-initiate Abilify MyCite and the second 
interventional period will proceed similarly to the interventional period (section 3.5.2). During this 
second, optional interventional period, patients may start and stop Abilify MyCite as clinically 
indicated.
Data collected at routine care visits between Day 180 and Day 360 will include Abilify MyCite use 
changes and AEs.
3.5.5
End of Study (Day 360)
The Day 360 visit marks the end of the second optional interventional phase. Data collected at the 
Day 360 visit includes Abilify MyCite use changes and AEs. 
 
 
3.5.6
Early Terminations
If a patient withdraws or is withdrawn from the study prematurely (e.g., before completing the 
scheduled Day 180 or Day 360 visit, if applicable), then an early termination (ET) visit should be 
performed, at which time all assessments and procedures that were to have been performed at the 
Day 180 or Day 360 (if applicable) visit should be completed. In such cases, the reason for the ET 
must be recorded.
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4.0 STATISTICAL METHODOLOGY
4.1 General Considerations
Statistical analyses will be performed using SAS® version 9.4 or higher computer software. 
Analyses will utilize prospectively collected clinical data from study sites, data collected from 
Abilify MyCite, 
 
 Data from all sources will be integrated into one dataset 
for analysis.
Patient characteristics, treatments and outcomes will be tabulated and summarized with descriptive 
statistics. All descriptive summaries will include means, medians, standard deviation (SD) and 
ranges for continuous variables and absolute/relative frequencies for categorical data. Statistics will 
be summarized for the study population overall and by treatment arm.
Raw data (i.e., minimum and maximum values presented for range in continuous variables) will be 
reported out to the precision with which it was collected. Means will be reported to 1 decimal place 
more than the raw data. SD will be reported to 1 decimal place more than the mean. Percentages 
will be reported to 1 decimal place. Trailing zeros will be presented to maintain a consistent level of 
precision, e.g. 2.0 rather than 2.
Inferential tests will be performed at the 5% level of significance. All p-values will be rounded to 3 
decimal places. If a rounded p-value is 0.000 (i.e., the actual p-value is less than 0.0005), then the 
p-value will be presented as ‘< 0.001.’
4.2 Sample Size Estimation
The primary endpoint for the study is the difference in the proportion of patients with at least 1 all-
cause hospitalization for the Abilify MyCite versus virtual matched control cohorts from baseline to 
Day 180. The sample size calculation assumptions were based on input 
 
 for patients diagnosed with SCH, BP1, or MDD who had at least 1 all-cause 
hospitalization or partial psychiatric hospitalization within the 60 days prior to enrollment. A 
control group event rate of 36.3% was estimated, weighted based on an expected study distribution 
of 25% patients with SCH, 25% with BP1, and 50% with MDD. Sample size calculations were 
based on testing 2 proportions using the Z-test with unpolled variance.
The study sample size of 447 patients was calculated based on the following assumptions, 
 
: 20% reduction in the proportion of patients with all-cause hospitalizations in the 
Abilify MyCite group versus the virtual matched control group (29.04% Abilify MyCite versus 
36.30% virtual matched control), 1:3 (Abilify MyCite:virtual matched controls) matching, 80% 
power, and maintaining an overall alpha level of 0.05 with the level of significance in a superiority 
hypothesis of 0.025. Using a 30% dropout rate at 6 months, a sample size of 640 patients will need 
to be enrolled to ensure completion of 447 patients.
A virtual control group of approximately 1350 patients will be identified 
 and 
matched to the final sample of Abilify MyCite patients. This will create 3 controls for every 1 
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Abilify MyCite patient, which reduces the required Abilify MyCite sample size as compared to a 
1:1 match while maintaining statistical power. Controls will be matched to Abilify MyCite patients 
using a propensity score (please see section 3.4) 
. If a
sufficient population of controls is not identified to support matching in a 1:3 (Abilify 
MyCite:virtual matched controls) ratio, the matching ratio will be decreased sequentially to 1:2 
followed by 1:1 if necessary.
4.3 Analysis of Demographic and Baseline Characteristics
Demographic and baseline characteristics will be summarized for the study population overall and 
by treatment (Abilify MyCite versus virtual matched controls). Discrete variables will be reported 
as count (frequency) and percent for each category. Continuous level variables (interval, ratio) will 
be reported as mean and standard deviation. Where applicable, range, minimum, maximum, and 
median will also be reported.
It is likely that the virtual matched controls will lack some variables that are available to the Abilify 
MyCite sample. As a result, a comprehensive list of each variable in the Abilify MyCite sample will 
be listed, while "N/A" will be listed for each variable that is not available in the virtual matched 
control cohort. Balance in baseline characteristics across the 2 cohorts will be evaluated prior to 
analysis.
4.4 Primary Endpoint
The primary endpoint is the difference in the proportion of patients with at least 1 all-cause 
hospitalization for the Abilify MyCite versus virtual matched control cohorts from baseline to Day 
180. The primary endpoint analysis will be a McNemar’s paired sample chi-square test between the 
treatment cohorts.
This test is directional in nature as it is testing the alternative hypothesis (HA) that the proportion 
patients hospitalized will be lower in the Abilify MyCite cohort than the virtual control cohort. 
Adjustments will be made to the alpha level to account for the one-tail nature of the alternative 
hypothesis.

H0: P1 – P2 ≥ 0 versus HA: P1 – P2 < 0
Where:

P1 = proportion of Abilify MyCite patients with all-cause hospitalization from baseline to 
Day 180

P2 = proportion of virtual control patients with all-cause hospitalization from baseline to 
Day 180
4.5 Secondary Endpoint
The secondary endpoint compares the difference between groups (Abilify MyCite versus virtual 
matched controls) in the proportion of patients with at least 80% PDC (with antipsychotic 
medication) from baseline to Day 180.
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4.6 Exploratory Endpoint
NA.
4.1 Missing data
Except where otherwise noted, missing data will not be imputed and will be excluded from the 
calculation of percentages.
It is likely that the virtual matched controls will lack some variables that are available to the Abilify 
MyCite sample. As a result, a comprehensive list of each variable in the Abilify MyCite sample will 
be listed, while "N/A" will be listed for each variable that is not available in the virtual matched 
control cohort.
4.2 Safety Analysis
All safety summaries will be descriptive in nature.
4.3 Other Analysis
There are no plans to include any other analysis other than what has been described above. Any 
post-hoc testing that might arise from the results or findings will be discussed and conducted in 
accordance with standard and accepted statistical procedures.
5.0 STATISTICAL ANALYSES
The study was earlier terminated after two subjects have enrolled and treated in the study; no 
efficacy assessment was obtained for these two subjects.  Thus, only patient baseline information of 
the two subjects is summarized.
5.1 Study Populations
5.1.1
Enrolled Population
The enrolled population includes all patients who signed informed consent and were enrolled in the 
study.
5.1.2
Analysis Population
The analysis population includes all patients who met all of the inclusion criteria and none of the 
exclusion criteria and completed a Day 180 study visit.
5.1.3
Safety Population
The safety population includes all patients who enrolled in the study and initiated use of Ability 
MyCite.
5.2 Efficacy Analysis
NA.


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5.3 Safety Analysis
All safety analyses for this study will be descriptive in nature and apply only to the Abilify MyCite 
group. Drug-related SAEs, device-related AEs including those leading to withdrawal from Abilify 
MyCite, potential hepatotoxicity cases, pregnancies, pregnancy-related outcomes will be coded 
Medical Dictionary for Regulatory Activities (MedDRA) using and descriptively summarized by 
System Organ Class (SOC) and Preferred Term (PT). Pregnancies and pregnancy-related outcomes 
will be summarized by those occurring in female patients versus those occurring in female partners 
of male patients.
5.3.1
AEs
For the purpose of this study, AEs that do not meet the definition for a “serious” AE (section 4.1.1 
and section 4.1.2 of the protocol) will only be collected if they are device-related (i.e., related to the
device component of Abilify MyCite, including those leading to withdrawal from Abilify MyCite.)
5.3.2
SAEs
All AEs meeting the definition of drug-related SAE (section 4.1.1 of the protocol) and device-related 
SAE (section 4.1.2 of the protocol) will be collected.
5.3.3
Potential Hepatotoxicity Cases
Potential hepatotoxicity cases will be collected with other AEs.
5.3.4
Pregnancy
Pregnancies occurring in female patients taking Ability MyCite during the study and within 30 days 
of the last dose of Abilify MyCite will be collected. Additionally, pregnancies occurring in female 
partners of male patients taking Ability MyCite during the study and within 90 days of the last dose 
of Abilify MyCite will be collected. Pregnancy, perinatal, and neonatal outcomes will be collected.  
6.0
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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7.0
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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_______________
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8.0
 
 
 
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9.0
 
 
 
 
 
 
 
 
 
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10.0
 
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11.0 APPENDIX F: Coding tables
Table 1: Mental health ICD diagnosis codes 
Condition
ICD-10 dx
Schizophrenia
F20.1x, F20.2x, F20.0x, F21.x, F20.5x, 
F20.89x, F20.3x, F20.9x
Depression
F32.x, F33.x
Bipolar 
disorder
F30.9x, F30.10x, F31.0x, F31.1x, F31.2x, 
F31.3x, F31.4x, F31.5x, F31.6x, F31.9x, 
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Table 2a: Non-LAI atypical antipsychotic GPI Codes
Brand Name
Generic Name
GPI Code
FANAPT
Iloperidone
59070035000310
59070035000320
59070035000340
59070035000360
59070035000380
59070035000385
59070035000390
FANAPT TITRATION PACK
Iloperidone
59070035006320
INVEGA
Paliperidone
59070050007505
59070050007510
59070050007520
59070050007530
PALIPERIDONE ER
Paliperidone                                        59070050007505
59070050007510
59070050007520
59070050007530
RISPERDAL
Risperidone
59070070000303
59070070000306
59070070000310
59070070000320
59070070000330
59070070000340
59070070002010
RISPERDAL M-TAB
Risperidone
59070070007220
59070070007230
59070070007240
59070070007250
59070070007260
RISPERIDONE
Risperidone
59070070000303
59070070000306
59070070000310
59070070000320
59070070000330
59070070000340
59070070002010
RISPERIDONE M-TAB
Risperidone
59070070007220
59070070007230
59070070007240
59070070007250
59070070007260


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RISPERIDONE ODT
Risperidone
59070070007210
59070070007220
59070070007230
59070070007240
59070070007250
59070070007260
QUETIAPINE FUMARATE
Quetiapine Fumarate
59153070100310
59153070100314
59153070100320
59153070100330
59153070100340
59153070100350
QUETIAPINE FUMARATE ER
Quetiapine Fumarate                           59153070107505
59153070107515
59153070107520
59153070107530
59153070107540
SEROQUEL
Quetiapine Fumarate
59153070100310
59153070100314
59153070100320
59153070100330
59153070100340
59153070100350
SEROQUEL XR
Quetiapine Fumarate
59153070107505
59153070107515
59153070107520
59153070107530
59153070107540
SAPHRIS
Asenapine Maleate                              59155015100710
59155015100720
59155015100730
OLANZAPINE
Olanzapine
59157060000305
59157060000310
59157060000315
59157060000320
59157060000330
59157060000340
59157060002120
OLANZAPINE ODT
Olanzapine                                          59157060007210
59157060007220
59157060007230
59157060007240


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ZYPREXA
Olanzapine
59157060000305
59157060000310
59157060000315
59157060000320
59157060000330
59157060000340
59157060002120
ZYPREXA ZYDIS
Olanzapine
59157060007210
59157060007220
59157060007230
59157060007240
ABILIFY
Aripiprazole
59250015000305
59250015000310
59250015000320
59250015000330
59250015000340
59250015000350
59250015002020
59250015002050
ABILIFY DISCMELT
Aripiprazole
59250015007220
59250015007230
ABILIFY MAINTENA
Aripiprazole                                        5925001500E430
5925001500E440
5925001500G230
5925001500G240
ARIPIPRAZOLE
Aripiprazole                                        59250015000305
59250015000310
59250015000320
59250015000330
59250015000340
59250015000350
59250015002020
ARIPIPRAZOLE ODT
Aripiprazole                                        59250015007220
59250015007230
REXULTI
Brexpiprazole                                      59250020000310
59250020000320
59250020000330
59250020000340
59250020000350
59250020000360
VRAYLAR
Cariprazine HCl                                  59400018100120
59400018100130


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59400018100140
59400018100150
5940001810B220
LATUDA
Lurasidone HCl
59400023100310
59400023100320
59400023100330
59400023100340
59400023100350
NUPLAZID
Pimavanserin Tartrate                         59400028200320
GEODON
Ziprasidone HCl
59400085100120
59400085100130
59400085100140
59400085100150
ZIPRASIDONE HCL
Ziprasidone HCl
59400085100120
59400085100130
59400085100140
59400085100150
GEODON
Ziprasidone Mesylate                          59400085202120


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Table 2b: LAI atypical antipsychotic GPI Codes
Brand Name
Generic Name
GPI Code
INVEGA SUSTENNA
Paliperidone Palmitate
59070050101837
59070050101838
59070050101839
59070050101840
59070050101845
INVEGA TRINZA
Paliperidone Palmitate                                 59070050101850
59070050101860
59070050101870
59070050101880
RISPERDAL CONSTA
Risperidone Microspheres
59070070101910
59070070101920
59070070101930
59070070101940
ZYPREXA RELPREVV
Olanzapine Pamoate
59157060101950
59157060101960
59157060101970
ABILIFY MAINTENA
Aripiprazole                                                59250015001920
59250015001930
ARISTADA
Aripiprazole Lauroxil                                   5925001520E420
5925001520E430
5925001520E440
5925001520E450


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