Clinical trial NCT06372210
Conditions: Mental Disorder Schizophrenia Major Depressive Disorder Bipolar I Disorder
Keywords: D-Tect patch
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Start date: 2023-06-26; Completion date: 2023-07-19
Enrollment: 54 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary purpose of the study is to evaluate the positive detection accuracy (PDA) and detection latency measures of the D-Tect patch.

Detailed description:
This is an open-label study to determine the accuracy of ingestible event marker (IEM) detection and detection latency of the D-Tect patch by completing a series of patch applications and IEM ingestions in the clinic.

The participants were enrolled in two cohorts within this study- Cohort 1: healthy participants received the placebo-embedded IEM tablets, Cohort 2: participants with serious mental illness (SMI) i.e schizophrenia, major depressive disorder, or bipolar I disorder received Abilify MyCite® tablets (aripiprazole-embedded IEM tablets).

This single-center trial was conducted in the United States. The overall time to participate in this study is up to approximately 17 days.

Arms: arm 1: A D-Tect patch was applied by the clinical staff prior to each IEM tablet ingestion, and directly observed ingestions (DOIs), followed by ingestion of 15 placebo-embedded IEM tablets, 1 every 15 minutes in Cohort 1 on Day 1 and a single dose of Abilify MyCite® tablet in Cohort 2 on Day 1.
Interventions: intervention 1: Placebo IEM tablet intervention 2: Abilify MyCite® intervention 3: D-Tect Patch
Intervention descriptions: intervention 1: Oral placebo-embedded IEM tablet. intervention 2: Oral aripiprazole-embedded IEM tablet. intervention 3: The D-Tect patch is a wearable sensor (WS) capable of detecting the ingestion of the IEM and measuring physiologic parameters. The WS automatically logs and stores the time when the IEM reaches the stomach and transmits the data to a smartphone.

Protocol documents:
Prot_000.pdf: 
Otsuka Pharmaceutical Development & Commercialization, Inc.
Aripiprazole (OPC-14597) Digital
CLINICAL PROTOCOL
Protocol Title: An Open-label, Prospective Trial Assessing Positive Detection Accuracy 
and Detection Latency Measures of the Miniature Ingestible Event Marker Tablet Using 
the D-Tect Patch in Healthy Subjects and Assessing Detection Latency Measures Using 
the D-Tect Patch in Subjects With Serious Mental Illness Taking Abilify MyCite Tablet 
Protocol Lay Person Short Title: A Trial to Assess a Wearable Patch’s Functioning to 
Detect Medication Ingestion
Protocol No. 031-201-00521
CONFIDENTIAL ⎯ PROPRIETARY INFORMATION
Trial Type:
Interventional 
Sponsor:
Otsuka Pharmaceutical Development & 
Commercialization, Inc. 
2440 Research Boulevard
Rockville, Maryland 20850, United States
Approval:
18 Apr 2023
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Table of Contents
Table of Contents ..........................................................................................2
List of In-text Tables.....................................................................................6
List of In-text Figures ...................................................................................7
List of Abbreviations.....................................................................................8
1
Protocol Summary ...............................................................................9
1.1
Synopsis ..............................................................................................................9
1.2
Schema ..............................................................................................................13
1.3
Schedule of Assessments ..................................................................................14
2
Introduction........................................................................................15
2.1
Trial Rationale...................................................................................................18
2.2
Background .......................................................................................................18
2.3
Known and Potential Risks and Benefits..........................................................18
2.3.1
D-Tect Patch...................................................................................................18
2.3.1.1
Skin Irritation..............................................................................................18
2.3.1.2
Allergic Reaction ........................................................................................19
2.3.2
Tablets ............................................................................................................19
2.3.3
COVID-19 Management Plan ........................................................................19
3
Objectives and Endpoints..................................................................19
4
Trial Design.........................................................................................20
4.1
Type/Design of Trial.........................................................................................20
4.2
Scientific Rationale for Trial Design ................................................................21
4.3
Dosing Rationale...............................................................................................21
4.4
Start and End-of-Trial Definitions ....................................................................21
4.5
Definition of Completed Subjects.....................................................................21
5
Trial Population .................................................................................21
5.1
Subject Selection and Numbering.....................................................................22
5.2
Eligibility Criteria .............................................................................................22
5.2.1
Inclusion Criteria............................................................................................22
5.2.2
Exclusion Criteria...........................................................................................23
5.3
Lifestyle Considerations....................................................................................23
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5.4
Screen Failures..................................................................................................23
6
Trial Device(s) and Concomitant Therapy ......................................24
6.1
Trial Device(s) Administered............................................................................24
6.1.1
Medical Devices .............................................................................................24
6.2
Management of Trial Device ............................................................................24
6.2.1
Packaging and Labeling .................................................................................24
6.2.2
Storage............................................................................................................25
6.2.3
Accountability ................................................................................................25
6.2.4
Returns and Destruction .................................................................................25
6.2.5
Reporting of Product Quality Complaints......................................................25
6.2.5.1
Eliciting and Reporting Product Quality Complaints.................................26
6.2.5.2
Information Required for Reporting Purposes............................................26
6.2.5.3
Return Process ............................................................................................27
6.2.5.4
Assessment/Evaluation ...............................................................................27
6.3
Measures to Minimize/Avoid Bias....................................................................27
6.4
Subject Compliance ..........................................................................................27
6.5
Dose Modification.............................................................................................27
6.6
Prior/Concomitant Medications or Therapies ...................................................27
6.7
Intervention After the End of the Trial .............................................................27
7
Discontinuation of Trial/Treatment and Subject 
Discontinuation/Withdrawal.............................................................28
7.1
Entire Trial or Treatment ..................................................................................28
7.2
Individual Site Discontinuation.........................................................................28
7.3
Discontinuation of Trial Device........................................................................28
7.3.1
Interruption of Trial Procedures .....................................................................28
7.4
Subject Discontinuation/Withdrawal from the Trial.........................................28
7.4.1
Documenting Reasons for Subject Discontinuation/Withdrawal...................29
7.5
Lost to Follow-up..............................................................................................30
8
Trial Procedures.................................................................................30
8.1
Efficacy Assessments........................................................................................33
8.2
Pharmacokinetic Assessments ..........................................................................33
8.3
Biomarker Assessments ....................................................................................34
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8.3.1
Pharmacodynamic Assessments.....................................................................34
8.4
Pharmacogenomic Assessments........................................................................34
8.5
Future Biospecimen Research Samples ............................................................34
8.6
Safety Assessments ...........................................................................................34
8.6.1
Skin Irritation Scoring System .......................................................................34
8.6.2
Clinical Laboratory Assessments ...................................................................34
8.6.3
Physical Examination .....................................................................................35
8.6.4
Vital Signs ......................................................................................................35
8.6.5
Electrocardiogram ..........................................................................................35
8.7
Adverse Events..................................................................................................35
8.7.1
Definitions ......................................................................................................35
8.7.2
Eliciting and Reporting Adverse Events ........................................................36
8.7.3
Immediately Reportable Events .....................................................................36
8.7.4
Medical Device Incidents (Including Malfunctions)......................................37
8.7.5
Adverse Events of Special Interest.................................................................37
8.7.6
Procedure for Breaking the Blind...................................................................37
8.7.7
Follow-up of Adverse Events.........................................................................37
8.7.7.1
Follow-up of Nonserious Adverse Events..................................................37
8.7.7.2
Follow-up of Immediately Reportable Events and Serious Adverse 
Events..........................................................................................................37
8.7.7.3
Follow-up and Reporting of Immediately Reportable Events 
Occurring After Last Scheduled Contact....................................................38
8.8
Treatment of Overdose......................................................................................38
8.9
Subject Assessment Recording .........................................................................38
8.10
Other Assessments ............................................................................................39
8.10.1
Positive Detection Accuracy ..........................................................................39
8.10.2
Detection Latency Measures ..........................................................................39
8.10.3
Sleep Diary .....................................................................................................39
9
Statistical Considerations..................................................................39
9.1
Sample Size.......................................................................................................39
9.2
Datasets for Analysis.........................................................................................39
9.3
Handling of Missing Data for Primary and Secondary Endpoint Analysis ......39
9.4
Statistical Analyses ...........................................................................................40
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9.4.1
Primary Endpoints..........................................................................................40
9.4.2
Secondary Endpoint........................................................................................40
9.4.2.1
Adverse Events ...........................................................................................40
9.4.2.2
Clinical Laboratory Data.............................................................................40
9.4.2.3
Physical Examination and Vital Signs Data ...............................................40
9.4.2.4
Electrocardiogram Data ..............................................................................40
9.4.3
Other Analyses ...............................................................................................41
9.4.3.1
Analysis of Demographic and Baseline Characteristics .............................41
9.5
Interim Analysis................................................................................................41
10
Supporting Documentation and Operational Considerations .......42
10.1
Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations ............42
10.1.1
Ethics and Responsibility ...............................................................................42
10.1.2
Informed Consent ...........................................................................................42
10.1.3
Recruitment Strategy......................................................................................43
10.1.4
Confidentiality................................................................................................43
10.1.5
Quality Control and Quality Assurance .........................................................43
10.1.5.1
Monitoring ..................................................................................................43
10.1.5.2
Auditing ......................................................................................................44
10.1.6
Protocol Deviations ........................................................................................44
10.1.7
Records Management .....................................................................................44
10.1.7.1
Source Documents ......................................................................................44
10.1.7.2
Data Collection ...........................................................................................45
10.1.7.3
File Management at the Trial Site...............................................................45
10.1.7.4
Records Retention at the Trial Site.............................................................46
10.1.7.5
Dissemination of Clinical Trial Data..........................................................46
10.1.7.6
Publication Authorship Requirements........................................................46
10.2
Appendix 2: Contraceptive Guidance and Collection of Pregnancy 
Information........................................................................................................48
10.3
Appendix 3: Protocol Amendments..................................................................49
10.3.1
Protocol Amendment(s)..................................................................................49
11
References...........................................................................................50
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List of In-text Tables
Table 1.3-1
Schedule of Assessments (Cohorts 1 and 2)..................................14
Table 3-1
Trial Objectives and Endpoints .....................................................19
Table 5.2.1-1
Inclusion Criteria (Cohort 1) .........................................................22
Table 5.2.1-2
Inclusion Criteria (Cohort 2) .........................................................22
Table 5.2.2-1
Exclusion Criteria (Cohort 1 and Cohort 2) ..................................23
Table 6.1.1-1
System Components to be Tested..................................................24
Table 8-1
Dosing Schedule ............................................................................32
Table 8.6.1-1
Skin Irritation Scoring System.......................................................34
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List of In-text Figures
Figure 1.2-1
Trial Design Schematic (Cohorts 1 and 2) ....................................13
Figure 2-1
Digital Medicine System ...............................................................15
Figure 2-2
D-Tect Patch Design......................................................................16
Figure 8-1
Wearable Sensor Placement Zones................................................31
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Abbreviation
Definition
AE
Adverse event
App
Application
CDC
Center for Disease Control
CFR
Code of Federal Regulations
CI
Confidence interval
CIOMS
Council for International Organizations of Medical Science
COVID-19
Coronavirus disease 2019
DMS
Digital Medicine System
DOI
Directly observed ingestion
DSM-5
Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition
eCRF
Electronic case report form
EDC
Electronic data capture
FDA
Food and Drug Administration
FOCBP
Females of childbearing potential
GCP
Good Clinical Practice
GPV
Global Pharmacovigilance
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Council for Harmonisation
ID
Identifier
IEM
Ingestible event marker
IRB
Institutional review board
IRE
Immediately reportable event
ITT
Intent-to-treat
MedDRA
Medical Dictionary for Regulatory Activities
MIT
Miniature ingestible event marker tablet
PDA
Positive detection accuracy
PQC
Product Quality Complaint
QC
Quality control
SAE
Serious adverse event
SMI
Serious mental illness
SmPC
Summary of Product Characteristics
SN
Serial number
SoA
Schedule of assessments
US
United States
USPI
United States Prescribing Information
WSs
Wearable sensors
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1
Protocol Summary
1.1
Synopsis
Name of Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Name of Investigational Device: Digital Medicine System (D-Tect Patch and Ingestible 
Event Markers [Miniature Ingestible Event Marker Tablet or Abilify MyCite Tablet])
Protocol No.: 031-201-00521
Protocol Title: An Open-label, Prospective Trial Assessing Positive Detection Accuracy 
and Detection Latency Measures of the Miniature Ingestible Event Marker Tablet Using 
the D-Tect Patch in Healthy Subjects and Assessing Detection Latency Measures Using 
the D-Tect Patch in Subjects With Serious Mental Illness Taking Abilify MyCite Tablet 
Protocol Lay Person Short Title: A Trial to Assess a Wearable Patch’s Functioning to 
Detect Medication Ingestion
Trial Type: Interventional 
Planned Treatment/Indication: Not applicable.
Trial Rationale: 
This two-cohort, open-label, prospective trial is designed to assess the positive detection 
accuracy (PDA) and detection latency of the D-Tect Patch. 
The PDA is defined as the proportion of miniature ingestible event marker tablets (MITs) 
detected out of the total ingestible event marker detections of tested D-Tect Patches 
(Cohort 1 only). 
For detection latency, Patch Detection Latency, Ingestion Data Transfer Latency, and 
Total Detection Latency will be measured for both cohorts (ie, MITs and Abilify 
MyCite). See Section 2 for the definition of the detection latency metrics.
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Objectives and Endpoints:
Objectives
Endpoints
Primary:
•
Evaluate PDA and detection latency measures 
for the D-Tect Patch. 
PDA: Estimate PDA with the CI lower limit 
greater than 95% when a subject is wearing the 
D-Tect Patch.
Detection Latency: The median Patch Detection 
Latency, Ingestion Data Transfer Latency, and 
Total Detection Latency.
Secondary: 
•
To collect and characterize adverse events 
associated with the device. 
Safety: The frequency and severity of AEs, 
device-related AEs, SAEs, AEs leading to 
discontinuation, and unanticipated adverse 
device effects.
AE = adverse event; CI = confidence interval; PDA = Positive Detection Accuracy; SAE = serious 
adverse event.
Trial Design:
This is a two-cohort, open-label, prospective trial designed to assess the PDA and 
detection latency of the D-Tect Patch. 
Trial Population:
Two cohorts of subjects will be enrolled in this trial.
Cohort 1: A minimum of 24 healthy subjects will be tested to obtain a minimum of 360 
miniature ingestible event marker tablet ingestions for Cohort 1. Healthy subjects will be 
drawn from nonvulnerable subpopulations. If a subject fails to complete participation in 
the testing, for whatever reason, a new, qualified candidate may be enrolled as a 
replacement.
Cohort 2: A minimum of 30 subjects with serious mental illness (SMI) will be tested to 
obtain a minimum of 30 Abilify MyCite ingestions for Cohort 2. These subjects will 
ingest Abilify MyCite at the same dose as their currently prescribed aripiprazole. If a 
subject fails to complete participation in the testing, for whatever reason, a new, qualified 
candidate may be enrolled as a replacement.
Key Inclusion/Exclusion Criteria:
Cohort 1: Male and female subjects greater than or equal to the age of 18 years, who are 
in good health, and who are able to provide informed consent will be considered for 
inclusion in the trial. Subjects with difficulty swallowing, active skin infection or history 
of inflammatory skin condition, or an allergy to adhesive bandages/tapes will be excluded 
from participation.
Cohort 2: Male and female subjects with SMI greater than or equal to the age of 18 years 
who are currently prescribed and taking aripiprazole and who are able to provide 
informed consent will be considered for inclusion in the trial. For the purposes of this 
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trial, SMI refers to subjects with a diagnosis of Schizophrenia, Major Depressive 
Disorder, or Bipolar I Disorder per Diagnostic and Statistical Manual of Mental 
Disorders - 5th Edition (DSM-5) criteria. Subjects with difficulty swallowing, active skin 
infection or history of inflammatory skin condition, or an allergy to adhesive 
bandages/tapes will be excluded from participation.
Trial Site(s): 
This trial will be a single-center trial conducted in the United States.
Trial Device:
The device and system components used in this trial are shown below:
Cohort
System Component
Description
Cohort 1
MIT (placebo embedded with 
an IEM) 
The MIT formulation is an IEM inside an inert tablet which 
will be dispensed to subjects to be ingested 15 times in 
1 day during the trial.
Cohort 2
Abilify MyCite tablet 
(aripiprazole embedded with 
an IEM) 
The Abilify MyCite formulation is an IEM inside an 
aripiprazole tablet which will be dispensed to subjects to be 
ingested one time during the trial.
Cohorts 
1 and 2
D-Tect Patch
A D-Tect Patch will be applied by clinic staff prior to 
DOIs.
Cohorts 
1 and 2
Computerized Device and 
Accessories
A computerized device (eg, smart phone) and accessories 
will be used by the clinic staff to track IEM detection on the 
software application.
DOI = directly observed ingestion; IEM = ingestible event marker; MIT = miniature ingestible event marker tablet.
Trial Assessments:
Assessments will include photographs of patches at application site, DOIs, Sleep Diary, 
and the Skin Irritation Scoring System (when applicable).
Independent Data Monitoring Committee: No
Statistical Methods:
The number of positive detection and PDA will be summarized for the D-Tect Patch for 
Cohort 1; the 95% confidence interval of PDA will be provided using the 
Clopper-Pearson method. A minimum of 24 subjects are planned to complete 15 DOIs 
per subject for Cohort 1. This will provide sufficient power to ensure the lower bound of 
the 95% confidence interval for PDA is at 95%, assuming the PDA rate of 97.3% of the 
D-Tect Patch using binomial distribution. 
Summary statistics will be provided for Patch Detection Latency, Ingestion Data Transfer 
Latency, and Total Detection Latency. Kaplan-Meier curves will be plotted for all of the 
latency times.
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Trial Duration:
The total duration the subject is expected to be on trial is approximately 8 days and 
includes the following visits:
•
Eligibility screening visit 
•
Testing Visit / Day 1 (1 day)
•
Follow-up / Day 8 (1 day)
The trial start is defined as the date the first subject signs their informed consent form. 
Overall, the trial duration, from signing of the first subject’s informed consent form to the 
last subject’s final assessment, is expected to be approximately 24 days.
Known and Potential Risks and Benefits:
It is anticipated that subjects will be exposed to minimal risk during this trial. Subjects 
will wear patches and ingest IEMs. Subjects in Cohort 2 will ingest Abilify MyCite at the 
same dose as their currently prescribed aripiprazole. Subjects may experience adverse 
events (AEs) due to the digital medicine system including, but not limited to, skin 
irritation or allergic reaction. No direct subject benefit is expected by participation in this 
trial. 
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1.2
Schema
aIf an in-person follow-up visit cannot occur due to severe acute respiratory syndrome coronavirus 
(SARS-CoV-2) restrictions (also known as coronavirus disease 2019 [COVID-19]), the site should 
conduct a follow-up video conference visit to verbally assess subject safety and instruct the subject to 
remove the patch at Day 8.
Figure 1.2-1
Trial Design Schematic (Cohorts 1 and 2)
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1.3
Schedule of Assessments
Table 1.3-1
Schedule of Assessments (Cohorts 1 and 2)
Period
Screening
Testing 
Follow-up
Visit
Visit 1
Visit 2a
Visit 3b,c
Trial Day
Day −7 to Day 1
Day 1
Day 8
(+2 days)
Informed Consent
X
Demographics
X
Medical History
X
Concomitant Medications 
X
X
X
Eligibility Criteria Review
X
Vital Sign Measurementsd
X
Preparation of application 
site and patch placement
X
Assessment of AEse 
X
X
X
Photograph of patches at 
application sitef 
X
X
DOIg,h
X
Sleep Diaryi
X
Patch Removalj
X
Pregnancy Testk
X
AE = adverse event; DOI = directly observed ingestion.
aConducted either on the same day as Visit 1, or up to 7 days after Visit 1.
bIn-person safety follow-up to occur 7 days after applying the patch.
cIf an in-person follow-up visit cannot occur due to COVID-19 restrictions, the site should conduct a 
follow-up visit via video conference to verbally assess subject safety and instruct the subject to 
remove the patch on Day 8.
dVital sign measurements include blood pressure, heart rate, temperature, height, and weight. 
eIf an AE is related to the patch, then the Skin Irritation Scoring System (Table 8.6.1-1) will be 
completed by the investigator.
fA minimum of 3 patch placement photos are required: prior to initial dose, after completion of DOI(s), 
and when the subject returns for follow-up (prior to patch removal).
gCohort 1: Subjects will ingest 15 miniature ingestible event marker tablets (MITs) over the course of 1 
visit day (with approximately 15 [−5 / +15] minutes between ingestions). 
hCohort 2: Subjects will ingest a single dose of Abilify MyCite at the same dose as their currently 
prescribed aripiprazole.
iOn Day 1 of the trial, subjects will be sent home with a sleep diary to complete each day until they 
return for the follow-up visit on Day 8 [+ 2 days].
jAny patch that falls off during the trial should be retained by the subject and given to trial staff during 
the in-person follow-up visit. All patches must be removed on Day 8, even if the clinic visit is 
delayed. 
kTo be collected from woman of childbearing potential via urine dipstick. 
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2
Introduction
The Digital Medicine System (DMS) has been designed to provide assistance with 
medication use and activities of daily living. The first DMS product (Abilify MyCite®) is 
approved by the United States Food and Drug Administration (FDA). When the 
ingestible event marker (IEM) is ingested, the DMS is intended to log, track, and trend 
intake times. When co-ingested with medication, the tracking and trending of intake 
times may be used as an aid to measure medication ingestion. Wearable sensors (WSs) or 
“patches” will be used to collect the raw signal data from the IEM. See Figure 2-1 for a 
visual of the DMS.
Figure 2-1
Digital Medicine System
Wearable Sensor 
The WS that will be utilized in this testing is the D-Tect Patch. The D-Tect Patch is an 
unmedicated, battery-powered, adhesive-backed device that is worn on the torso 
(Figure 2-2). The WS contains electronic sensors capable of detecting the ingestion of the 
IEM and of measuring physiologic parameters. The WS automatically logs and stores the 
time when the IEM reaches the stomach and is activated and also automatically records 
and stores physiologic data and activities of daily living. Contact of the patch to the skin 
is made by conductive gel electrodes. Adequate quality of the patch-to-skin contact is 
assessed by determining an impedance value (in ohms) between the skin and the patch 
periodically (eg, every 20 minutes).
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Figure 2-2
D-Tect Patch Design
In this trial, the D-Tect Patch should remain on the torso until removed by trial staff at the 
in-person follow-up visit. The patch placement zones are shown in Figure 8-1. Any patch 
that falls off during the trial must be retained by the subject and given to trial staff during 
the in-person follow-up visit. 
Ingestible Event Marker
The IEM is a tiny device that is composed of a 1 mm x 1 mm x 0.3 mm silicon integrated 
circuit coated with thin layers of minerals and metals that rests in the center of an edible, 
cellulose-based disc. Within a few minutes after ingestion, the sensor uses the fluid in the 
stomach (pH independent) to provide the electrolyte for a biogalvanic battery formed by 
thin layers of the essential dietary minerals, magnesium, and copper deposited on the 
sensor’s surface. The ensuing current is modulated by the IEMs microprocessor and 
creates an electric field that propagates through the body tissues to the skin surface. The 
modulated current is detected, decoded, recorded, and date- and time-stamped by the 
patch, which acts as a receiver. The IEM communicates with its identifier for a finite 
period of time of a few minutes and can be detected by the patch only when the patch is 
adherent to the subject’s skin, thus providing personal privacy for data recording. This 
mimics the process whereby bioelectric signals from cardiomyocytes reach the electrodes 
of an electrocardiograph on the surface of the body. Each sensor’s identifier is unique 
which makes it possible to differentiate multiple IEMs from one another when they are 
ingested at the same time. The IEM becomes inactive subsequently and is excreted in the 
feces. The IEM consists of tiny amounts of naturally occurring minerals found in the 
body and in food. 
For this trial, testing will involve directly observed ingestions (DOIs) of the IEMs. 
Research staff will administer the IEMs to subjects and observe and record the time of 
each individual ingestion event. 
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•
For Cohort 1: The miniature IEM tablet (MIT) dose form will be used for testing. 
There are no active pharmaceutical ingredients in this dose form. Subjects will take 
15 MITs over the course of 1 day, with approximately 15 (−5 / +15) minutes between 
ingestions.
•
For Cohort 2: A single dose of Abilify MyCite (aripiprazole embedded with an IEM) 
will be used for testing. Abilify MyCite will be dispensed to subjects at the same dose 
as their current aripiprazole prescription. Abilify MyCite will be ingested at one time 
point during the trial. 
Mobile Device with Mobile Application
The DMS also includes an application (app) software that is installed on a mobile device 
(eg, smartphone), which aggregates and displays the Otsuka WS data. The wireless 
Bluetooth-based interface within the WS is activated to transmit its stored encrypted data 
in a secure manner. The data transmitted by the WS include the IEM information, the WS 
serial number, impedance, and battery level and the physiologic parameters. 
One mobile device will be provided to pair with the D-Tect Patch on the Testing Day 
during the DOI(s). All patches will be worn until the in-person follow-up visit. Software 
will be preloaded or loaded remotely (wirelessly) once testing has begun. Subjects will 
not be required to interact with the mobile device.
Please refer to the OPC-14597 Digital (Digital Medicine-Aripiprazole) Investigator’s 
Brochure (IB) for more detailed information of the chemistry, pharmacology, efficacy, 
and safety of the DMS.
Detection Latency Metrics
There are 4 time-stamped events associated with measuring detection latency. These 4 
events are shown in the system diagram in Figure 2-1 and further described below.
1) Subject takes tablet. Directly observed ingestion time is recorded by the clinician. 
2) Tablet sends signal to the patch. Tablet is detected & recorded by the patch as an 
IEM record with a timestamp.
3) Patch sends ingestion data to phone. The tablet ingestion data is communicated to 
and recorded by the mobile device as a pill-ingestion-metric with a timestamp. 
4) Tablet ingestion data is displayed. The tablet display event is triggered on the 
mobile device as a pill-display-event with a timestamp.
The latency between each of these timestamps is defined as:
•
“Patch Detection Latency” is the time between steps 1) and 2) 
•
“Ingestion Data Transfer Latency” is the time between steps 2) and 4) 
•
“Total Detection Latency” is the total time between steps 1) to 4)
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2.1
Trial Rationale
This two-cohort, open-label, prospective trial is designed to assess the positive detection 
accuracy (PDA) and detection latency of the D-Tect Patch. 
The PDA is defined as the proportion of MITs detected out of the total IEM detections of 
tested D-Tect Patches (Cohort 1 only). 
For detection latency, Patch Detection Latency, Ingestion Data Transfer Latency, and 
Total Detection Latency will be measured for both cohorts (ie, MITs and Abilify 
MyCite). See Section 2 for the definition of the detection latency metrics.
2.2
Background
A new generation patch, the D-Tect Patch, has been developed for use in the DMS. The 
D-Tect Patch was designed to be thinner, more flexible, and contain less adhesive than 
predecessor patches. This trial is designed to collect the PDA (Cohort 1 only) and 
detection latency of the D-Tect Patch and involves 2 cohorts of subjects:
•
Cohort 1 includes healthy subjects who will ingest MITs.
•
Cohort 2 includes subjects with serious mental illness (SMI) (ie, Schizophrenia, 
Major Depressive Disorder, or Bipolar I Disorder) who are already prescribed and 
taking aripiprazole prior to trial entry. These subjects will ingest Abilify MyCite at 
the same dose as their currently prescribed aripiprazole.
2.3
Known and Potential Risks and Benefits
It is anticipated that subjects will be exposed to minimal risk during this trial. Subjects 
will be asked to wear a patch and ingest IEMs (MITs or Abilify MyCite). Subjects may 
experience adverse events (AEs) due to the DMS including, but not limited to, skin 
irritation or allergic reaction. No direct subject benefit is expected by participation in this 
trial. 
The trial site will receive the IB, and the trial site should refer to the most current version 
as needed.
2.3.1
D-Tect Patch
2.3.1.1
Skin Irritation
Skin irritation may result from wearing the D-Tect Patch over the course of the wear 
period or from removing the patch. 
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2.3.1.2
Allergic Reaction
An allergic reaction could potentially arise from exposure to components of the patch 
adhesive. 
To mitigate the risk of this potential hazard, prospective subjects who have a known 
allergy to skin adhesives will be excluded from the trial. Allergy to bandages, tapes, and 
latex will be specifically queried.
Subjects will be told that they are free to remove the patches at any time and to inform 
the clinical research site immediately. Subjects will also be told to reach out for 
emergency medical care should they have immediate need for medical attention.
2.3.2
Tablets
For Cohort 1, the MIT dose form does not contain active pharmaceutical ingredients. 
For Cohort 2, subjects will ingest Abilify MyCite at the same dose as their currently 
prescribed aripiprazole. Abilify is contraindicated in patients who are hypersensitive to 
aripiprazole or any of the excipients. Refer to the United States Prescribing Information 
(USPI) and Summary of Product Characteristics (SmPC) for complete warnings and 
precautions. All known drug interactions and other forms of interactions are described in 
the USPI and SmPC.
2.3.3
COVID-19 Management Plan
The clinical research site is expected to adhere to all United States Center for Disease 
Control (CDC), state, and local coronavirus disease 2019 (COVID-19) guidelines.
3
Objectives and Endpoints
Table 3-1
Trial Objectives and Endpoints
Objectives
Endpoints
Primary:
•
Evaluate PDA and detection latency measures 
for the D-Tect Patch.
PDA: Estimate PDA with the CI lower limit 
greater than 95% when a subject is wearing the 
D-Tect Patch.
Detection Latency: The median Patch Detection 
Latency, Ingestion Data Transfer Latency, and 
Total Detection Latency. See Section 2 for the 
definition of the detection latency metrics.
Secondary: 
•
To collect and characterize AEs associated with 
the device. 
Safety: The frequency and severity of AEs, 
device-related AEs, serious AEs (SAEs), AEs 
leading to discontinuation, and unanticipated 
adverse device effects.
AE = adverse event; CI = confidence interval; PDA = Positive Detection Accuracy; SAE = serious 
adverse event.
Section 9.4 describes the statistical analysis of the endpoints.
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4
Trial Design
4.1
Type/Design of Trial
This two-cohort, open-label, prospective trial is designed to assess the PDA and detection 
latency of the D-Tect Patch. 
Cohort 1
Cohort 1 will be completed in adult, healthy subjects. Subjects in Cohort 1 will take the 
MIT dose form. This trial will consist of up to 3 onsite visits including:
•
Visit 1: Screening
•
Visit 2 (Day 1): Testing, patch placement, DOI of MITs (conducted either on the 
same day as Visit 1 or up to 7 days after Visit 1)
•
Visit 3 (Day 8): In-person safety follow-up and removal of patch (conducted 
approximately 7 days [+ 2 days] after applying the D-Tect Patch). 
Cohort 2
Cohort 2 will be completed in adults with SMI who are prescribed and taking aripiprazole 
prior to trial entry. Subjects will take a single dose of Abilify MyCite at the same dose as 
subject’s current aripiprazole prescription. Subjects will be instructed not to take their 
currently prescribed dose of aripiprazole at home on Day 1 of the trial when Abilify 
MyCite will be ingested. This trial will consist of up to 3 onsite visits including:
•
Visit 1: Screening
•
Visit 2 (Day 1): Testing, patch placement, DOI of a single dose of Abilify MyCite 
(conducted either on the same day as Visit 1 or up to 7 days after Visit 1)
•
Visit 3 (Day 8): In-person safety follow-up and patch removal (approximately 7 days 
[+ 2 days] after applying the D-Tect Patch) 
Cohorts 1 and 2
No trial procedures may be conducted prior to signing of the informed consent form 
(ICF), which will occur at Visit 1. Visit 2 involves patch application and DOI(s). Visits 1 
and 2 may be combined and conducted on the same day. Subjects will return to the site 
on Day 8 (+ 2 days), 7 days following patch placement for a safety follow-up evaluation 
and to make final observations of patch wear (Visit 3). Any patches that remain on the 
subject will be removed at this visit. Any patch that falls off prior to the safety follow-up 
visit should be retained by the subject and given to trial staff at the scheduled follow-up 
visit. 
A detailed schedule of events can be found in Table 1.3-1.
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4.2
Scientific Rationale for Trial Design
The D-Tect Patch is a new generation patch that has been developed for use in the DMS. 
Predecessor patches used in conjunction with the DMS were tested for packet detection 
performance as well as detection latency. This trial is being conducted to demonstrate 
that the D-Tect Patch performance is comparable to predecessor patch data. 
4.3
Dosing Rationale
In Cohort 1, no medication will be ingested. 
In Cohort 2, subjects will ingest a single dose of Abilify MyCite (aripiprazole embedded 
with an IEM) at the same dose as their currently prescribed aripiprazole. The following 
doses of Abilify MyCite are available for use in this trial: 2 mg, 5 mg, 10 mg, 15 mg, 
20 mg, and 30 mg. The dose of Abilify MyCite will be recorded in subject’s source 
documentation and the electronic case report form (eCRF). 
4.4
Start and End-of-Trial Definitions
The trial start is defined as the first visit of the first subject, which is the date the first 
subject signs their ICF.
The end-of-trial date is defined as the last date of contact, or the date of final contact 
attempt as recorded in subject’s source documentation for the last subject completing or 
withdrawing from the trial.
4.5
Definition of Completed Subjects
The trial period is defined as the time period during which subjects are evaluated for the 
primary objective of the trial irrespective of whether or not the subject wears the patch or 
ingests all IEMs. Subjects who are evaluated at the last scheduled visit will be defined as 
trial completers. 
5
Trial Population
Two cohorts of subjects will be enrolled in this trial. 
Cohort 1: A minimum of 24 healthy subjects will be tested to obtain a minimum of 
360 miniature IEM tablet ingestions for Cohort 1. Healthy subjects will be drawn from 
nonvulnerable subpopulations. If a subject fails to complete participation in the testing, 
for whatever reason, a new, qualified candidate may be enrolled as a replacement.
Cohort 2: A minimum of 30 subjects with SMI will be tested to obtain a minimum of 
30 Abilify MyCite ingestions for Cohort 2. Subjects will ingest Abilify MyCite at the 
same dose as their currently prescribed aripiprazole. If a subject fails to complete 
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participation in the testing, for whatever reason, a new, qualified candidate may be 
enrolled as a replacement.
5.1
Subject Selection and Numbering
All subjects will be given a unique subject identifier (ID; site number [3 digits] + subject 
number [‘S’ + 5 digits] upon providing consent). The site number will be designated by 
the sponsor. The subject number will be given sequentially from S00001.
Demographic information (date of birth, sex at birth, gender identification, childbearing 
potential, race, ethnicity) and medical history will be recorded in the eCRF at the 
screening visit.
5.2
Eligibility Criteria
Exceptions for eligibility criteria will not be permitted during the trial, neither by the 
investigator nor by the sponsor.
5.2.1
Inclusion Criteria
Subjects are required to meet the inclusion criteria shown in Table 5.2.1-1 to participate 
in Cohort 1 of the trial:
Table 5.2.1-1
Inclusion Criteria (Cohort 1)
1.
Have read, reviewed with trial site staff, and signed the informed consent.
2.
Male or female at least 18 years of age.
3.
In good general health or medically stable.
4.
Is able and willing to participate in, and adhere to, all testing procedures, both onsite and offsite, 
for the entire testing.
5.
Subject has access to a telephone for communicating with the trial personnel and for trial 
personnel to contact the subject.
Subjects are required to meet the inclusion criteria shown in Table 5.2.1-2 to participate 
in Cohort 2 of the trial:
Table 5.2.1-2
Inclusion Criteria (Cohort 2)
1.
Have read, reviewed with trial site staff, and signed the informed consent.
2.
Male or female at least 18 years of age.
3.
In good general health or medically stable.
4.
Has confirmed diagnosis of Schizophrenia, Major Depressive Disorder, or Bipolar I Disorder per 
Diagnostic and Statistical Manual of Mental Disorders - 5th Edition (DSM-5) criteria and currently 
prescribed and taking aripiprazole.
5.
Is able and willing to participate in, and adhere to, all testing procedures, both onsite and offsite, 
for the entire testing.
6.
Subject has access to a telephone for communicating with the trial personnel and for trial personnel 
to contact the subject.
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5.2.2
Exclusion Criteria
Subjects will be excluded from Cohort 1 and/or Cohort 2 if they meet any of the 
exclusion criteria shown in Table 5.2.2-1:
Table 5.2.2-1
Exclusion Criteria (Cohort 1 and Cohort 2)
1.
Any medical condition, treatment, or symptoms that, in the judgment of the trial clinician, could 
place the subject at more than the minimal risk from involvement in the testing.
2.
Hospitalization, emergency room visit, surgery or new medical treatment within 30 days before 
testing begins or planned during testing.
3.
Difficulty with or inability to swallow tablets.
4.
Active skin infection or active dermatitis, OR history of chronic inflammatory skin condition 
including psoriasis and chronic dermatitis (except atopic dermatitis).
5.
The investigator will determine if any subject should be excluded from the trial based on history of, 
OR current, alcohol abuse, drug abuse or use of illegal drugs (eg, amphetamines or heroin).
6.
Allergy to adhesive bandages/tapes (eg, Band-Aids®) or latex.
7.
Positive urine pregnancy test at screening visit (dipstick).
8.
Subject is taking any concomitant medication that places the subject at a greater risk for skin 
reactions or skin sensitivity.
A definition of childbearing potential can be found in Section 10.2.
5.3
Lifestyle Considerations
Not applicable.
5.4
Screen Failures
A screen failure is a subject from whom informed consent is obtained and is documented 
in writing (ie, subject signs an ICF), but who does not have a patch applied. All AEs must 
be reported after subject informed consent has been obtained, including screen failures 
due to AEs, irrespective of trial intervention administration.
If the subject meets the definition of a screen failure in this trial, the following 
information will be recorded in the eCRF:
•
Date of ICF signature
•
Visit date (screening visit)
•
Demographics 
•
Result of eligibility assessment
•
Screen failure date
•
Reason for screen failure
•
Any AEs
Individuals who do not meet the criteria for participation in this trial (screen failure) may 
not be rescreened.
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6
Trial Device(s) and Concomitant Therapy
6.1
Trial Device(s) Administered
Trial devices intended to be administered to the subjects during the conduct of the trial 
are listed in Table 6.1.1-1.
For information regarding the dose and observation period(s), including any follow-up 
period for the trial, see Section 4.1.
6.1.1
Medical Devices
The system components used in this trial are shown below in Table 6.1.1-1.
Table 6.1.1-1
System Components to be Tested 
Cohort
System Component
Description
Cohort 1
MIT (placebo embedded with 
an IEM) 
The MIT formulation is an IEM inside an inert tablet which 
will be dispensed to subjects to be ingested 15 times in 
1 day during the trial.
Cohort 2
Abilify MyCite tablet 
(aripiprazole embedded with 
an IEM) 
The Abilify MyCite formulation is an IEM inside an 
aripiprazole tablet which will be dispensed to subjects to be 
ingested one time during the trial.
Cohorts 
1 and 2
D-Tect Patch
A D-Tect Patch will be applied by clinic staff prior to 
DOIs.
Cohorts 
1 and 2
Computerized Device and 
Accessories
A computerized device (eg, smart phone) and accessories 
will be used by the clinic staff to track IEM detection on the 
software application.
6.2
Management of Trial Device
For full details on management of trial device(s), please refer to the trial-specific 
operations manual.
6.2.1
Packaging and Labeling
The D-Tect Patches will be provided by the sponsor or designated agent to the site. The 
D-Tect Patches will be supplied in pouches. Each patch used will be labeled to clearly 
disclose the unique patch serial number (SN) and lot number. The SN and lot number will 
be recorded in the eCRF. 
The IEMs (MITs and Abilify MyCite) will be provided by the sponsor or designated 
agent to the investigators and the persons designated by the investigator(s) or 
institution(s). The MITs and Abilify MyCite will be supplied in bottles. For Abilify 
MyCite, 1 bottle of each dose will be supplied to the site. 
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6.2.2
Storage
The device and components (ie, patches and IEMs [MITs and Abilify MyCite]) will be 
stored in a securely locked cabinet or enclosure. MITs and Abilify MyCite must be stored 
in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff. 
6.2.3
Accountability
The investigator or designee must maintain an inventory record of the D-Tect Patches, 
IEMs (MITs and Abilify MyCite), and mobile device(s) received, dispensed, 
administered, returned, and lost (if applicable). Neither the investigator nor any designees 
may provide a device to any subject not participating in this trial.
6.2.4
Returns and Destruction
The mobile devices will be returned to the sponsor representatives after completion of all 
ingestions on Day 1.
The D-Tect Patches will be collected by the sponsor representatives after accountability. 
Upon completion or termination of the trial, all used and unused D-Tect Patches must be 
returned to the sponsor or a designated agent. All D-Tect Patches returned to the sponsor 
must be accompanied by the appropriate documentation and be clearly identified by 
protocol number and trial site number on the outermost shipping container. Returned 
D-Tect Patches should be in the original containers and used patches should be stuck to 
the inside of a zip lock bag. The assigned trial monitor will facilitate the return of used 
and unused D-Tect Patches. 
Tablets (MITs and/or Abilify MyCite) may be returned to the sponsor and/or destroyed 
by the clinical trial site following completion and verification of accountability. Refer to 
the Pharmacy Manual for instructions on returns and/or destruction. 
6.2.5
Reporting of Product Quality Complaints
Product Quality Complaints (PQCs) will be reported for Abilify MyCite tablets only. 
PQCs will not be reported for the D-Tect Prototype Patch, MIT dose form, or app.
A PQC is any written, electronic, or oral communication provided by a healthcare 
professional, consumer, clinical trial subject, medical representative, regulatory agency, 
partner, or other third party that alleges deficiencies related to the identity, quality, 
durability, reliability, safety, effectiveness, or performance of a medical device or 
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medicinal product or a falsified, tampered, or diverted product after it is released for 
distribution.
Examples include, but are not limited to, communications involving:
•
Failure of a product to meet any of its specifications.
•
Incorrect or missing labeling.
•
Packaging issues: (eg, damaged, dirty, crushed, missing tablet, missing patch/pod, 
missing component). 
•
Tablet/bottle defects: (eg, odor, under-filled bottle, empty bottle, over-filled bottle, 
tablet not registering with the app, chipped tablet, broken tablet).
•
Loss or theft of product.
6.2.5.1
Eliciting and Reporting Product Quality Complaints
The investigator or designee must record each PQC identified through any means from 
the receipt of the Abilify MyCite tablets from the sponsor or sponsor’s designee, through 
and including reconciliation and up to destruction, including subject dosing. The 
investigator or designee must notify the sponsor (or sponsor’s designee) within 24 hours 
of becoming aware of the PQC according to the procedure outlined below.
Send PQC reporting information to the OPDC IMP complaints mailbox email:
Email: IMP-PQC@otsuka-us.com 
Also indicate whether or not the complaint sample is available for return.
Identification of a PQC by the subject should be reported to the site investigator, who 
should then follow the reporting mechanism above.
6.2.5.2
Information Required for Reporting Purposes
•
Description of complaint
•
Reporter identification (eg, subject, investigator, site, etc)
•
Reporter contact information (eg, address, phone number, email address)
•
Subject number
•
Clinical site number
•
ID of material (product/compound name, lot/batch number, shipment number, expiry 
date)
•
Clinical protocol reference (number and/or trial name)
•
Dosage form/strength (if known)
•
Pictures of complaint sample (if available)
•
Availability of complaint sample for return
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6.2.5.3
Return Process
Indicate during the report of the PQC if the complaint sample is available for return. 
If the complaint sample is available for return, the return instructions will be provided by 
the sponsor.
It must be documented in the site accountability record that the complaint sample has 
been forwarded to the sponsor for complaint investigation.
6.2.5.4
Assessment/Evaluation
Assessment and evaluation of PQCs will be handled by the sponsor.
6.3
Measures to Minimize/Avoid Bias
This is an open-label trial. 
6.4
Subject Compliance
A subject will be withdrawn from the trial by the investigator (or designee) if the subject 
is noncompliant with the protocol (defined as refusal or inability to adhere to the trial 
schedule or procedures) and the details will be recorded on the appropriate eCRF. 
6.5
Dose Modification
Not applicable. Subjects in Cohort 2 will be administered a single dose of Abilify MyCite 
at the same dose as their currently prescribed aripiprazole dose. 
6.6
Prior/Concomitant Medications or Therapies
The investigator will record all medications (including, but not limited to, prescription 
medications, over-the-counter medications, vitamins, herbal remedies, etc) and therapies 
taken by the subject from 7 days prior to D-Tect Patch application through the end of the 
evaluation period (defined as the time period during which subjects are evaluated for 
primary and/or secondary objectives) in the eCRF. The investigator will also record all 
medications and therapies taken by the subject for treatment of an AE or which caused an 
AE until the end of the trial (defined as the last date of contact or date of final contact 
attempt) in the eCRF.
6.7
Intervention After the End of the Trial
Not applicable. 
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7
Discontinuation of Trial/Treatment and Subject 
Discontinuation/Withdrawal
7.1
Entire Trial or Treatment
If the sponsor terminates or suspends the trial for any reason, prompt notification will be 
given to investigators, institutional review boards (IRB), and regulatory authorities in 
accordance with regulatory requirements.
7.2
Individual Site Discontinuation
Individual trial site participation may be discontinued by the sponsor, the investigator, or 
the IRB if judged to be necessary for medical, safety, regulatory, ethical or other reasons 
consistent with applicable laws, regulations, and Good Clinical Practice (GCP). The 
investigator will notify the sponsor promptly if the investigator or the IRB at the site 
discontinues participation in the trial.
7.3
Discontinuation of Trial Device 
Under certain circumstances, it may be necessary for a subject to permanently 
discontinue the trial. If trial IEMs or patches are permanently discontinued, the subject 
should, if at all possible, remain in the trial to be evaluated for safety assessments. See 
the schedule of assessments (SoA) for data to be collected at the time of discontinuation 
of trial device and follow-up and for any further evaluations that need to be completed. If 
a subject discontinues the trial due to an AE, the investigator, or other trial personnel, will 
make every effort to follow the event until it has resolved or stabilized.
For each subject who discontinues the trial, the main reason for discontinuation will be 
recorded in the eCRF (refer to Section 7.4.1).
7.3.1
Interruption of Trial Procedures
If a subject temporarily interrupts trial device use due to an AE, the investigator, or other 
trial personnel, will make every effort to follow the event until it has resolved or 
stabilized. For each subject who has an interruption in trial device use, the main reason 
for interruption will be recorded in the eCRF.
7.4
Subject Discontinuation/Withdrawal from the Trial
•
A subject may withdraw from the trial at any time at the subject’s own request for any 
reason (or without providing any reason).
•
A subject may be withdrawn at any time at the discretion of the investigator for 
safety, behavioral, or compliance reasons. 
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•
At the time of discontinuing from the trial, if possible, an early discontinuation visit 
should be conducted to assess any new or ongoing AEs. 
•
If a subject withdraws consent from the trial, the subject will be permanently 
discontinued from all trial procedures and the trial.
•
If the subject withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before the withdrawal of consent.
Complete withdrawal of consent requires a subject’s refusal of ALL of the following 
methods of follow-up:
•
Participation in all follow-up procedures specified in the protocol (whether in-clinic, 
by telephone, or by a home visit).
•
Participation in a subset of protocol-specified follow-up procedures (by a frequency 
schedule and method, as agreed by subject and trial site staff).
•
Contact of the subject by trial site staff, even if only by telephone, to assess current 
medical condition, and obtain necessary medical reports relevant to the trial’s 
objectives.
•
Contact of alternative person(s) who have been designated in source records as being 
available to discuss the subject’s medical condition, even if only by telephone, mail, 
or email (eg, family, spouse, partner, legal representative, friend, neighbor, or 
physician).
•
Access to medical information from alternative sources (eg, hospital/clinic medical 
records, referring doctor’s notes, public records, dialysis, transplantation or vital 
registries, social media sources).
Withdrawal of consent is a critical trial event and, therefore, should be approached with 
the same degree of importance and care as is used in initially obtaining informed consent. 
The reasons for a subject’s intended withdrawal need to be completely understood, 
documented, and managed to protect the rights of the subject and the integrity of the trial. 
Only subjects who withdraw their permission for all of the above methods of follow-up 
are considered to have completely withdrawn their consent to participate in the trial.
7.4.1
Documenting Reasons for Subject Discontinuation/Withdrawal
A subject may discontinue the trial or withdraw from the trial for the reasons listed 
below:
•
Adverse event

Continuing investigational device and/or ingestion of IEMs (MITs and/or Abilify 
MyCite) places the subject at undue risk as determined by the investigator (eg, a 
safety concern that is possibly, probably, or likely related to the investigational 
device or its components)

Serious adverse event (SAE)

Other potentially investigational device-related safety concerns or AEs
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•
Death
•
Lost to follow-up
•
Physician decision
•
Pregnancy
•
Protocol deviation
•
Protocol-specific withdrawal criterion met
•
Site terminated by sponsor
•
Withdrawal by subject
7.5
Lost to Follow-up
Subjects who cannot be contacted on or before Visit 3 (Day 8 [+ 2 days]) during the trial 
period, who do not have a known reason for discontinuation (eg, withdrew consent or 
AE), and for whom a survival status at the end of the trial cannot be determined will be 
classified as “lost to follow-up.” 
The site will make 3 documented attempts to contact the subject by telephone and in the 
event the site is unable to reach the subject by telephone, the site will attempt to contact 
the subject via certified mail or an alternative similar method, where appropriate, before 
assigning a “lost to follow-up” status.
If the subject was classified as “lost to follow-up,” the following information will be 
recorded in the eCRF: “Date of final contact attempt” and “Contact method.”
8
Trial Procedures
This trial consists of up to 3 days of onsite testing activities, including the screening visit, 
testing visit (conducted either on the same day as Visit 1 or up to 7 days after Visit 1), 
and the in-person safety follow-up visit, which will occur on Day 8 (+ 2 days). The 
D-Tect Patch will be worn until the in-person follow-up visit. Consent will be obtained 
from subjects prior to conduct of any testing related assessments or procedures in a 
manner consistent with GCP. 
The assessments to be conducted during the trial are summarized in Table 1.3-1.
Screening 
The informed consent process will be administered at Visit 1. The investigator (or 
designee) will determine whether a subject meets all eligibility criteria. In addition to 
gathering information specifically pertaining to the eligibility criteria, the investigator (or 
designee) will conduct a brief health screen. Only responses related to the eligibility 
criteria will be recorded in the eCRF. The investigator (or designee) will include this 
assessment in determining whether the level of risk for an individual is acceptable for 
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participating in testing and will record whether the risk is acceptable on the appropriate 
screening eCRF. All recorded information will be de-identified. A physical examination 
is not required to be performed as part of screening, although evaluation of any 
subsequent AEs may require a targeted exam by a member of the clinical staff. Subjects 
will be instructed not to take their prescribed dose of aripiprazole on Day 1 of the trial.
Testing Visit 
The research staff will meet with subjects for activities specified in Table 1.3-1 including 
assessment of AEs, review of concomitant medications, preparation of skin for patch 
placement, patch placement and photographs, DOI(s), and administration of the Sleep 
Diary. Subjects’ food and drink intake on the Testing Day will be recorded by clinic staff.
Trained research staff will prepare subject skin to ensure good patch adhesion and place 
the D-Tect Patch on the subject. Skin preparation techniques may include cleansing of the 
skin with the provided “Simple” brand wipes, and/or clipping or shaving of excessive 
hair. To place the D-Tect Patch, the subject will be required to temporarily shift their 
shirt (and undergarments, if applicable) to allow access to the upper body. Even 
numbered subjects will have one D-Tect Patch placed on the right costal margin, 
anywhere from the xiphoid to the right mid-axillary line. Odd numbered subjects will 
have one D-Tect Patch on the left costal margin, anywhere from the xiphoid to the left 
mid-axillary line as shown in Figure 8-1. 
Figure 8-1
Wearable Sensor Placement Zones
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After the D-Tect Patch is successfully placed, the subject can readjust their clothes. Staff 
will confirm that no patch placed comes into contact with the wire within a bra (where 
applicable). Non-site trial staff may perform quality control (QC) of patch placement on 
subjects. Patch placement photographic evidence will be documented. A minimum of 3 
patch placement photos is required:
1) Prior to initial dose
2) After completion of the 15th MIT dose (Cohort 1) or after completion of the 
single dose of Abilify MyCite (Cohort 2)
3) When the subject returns for follow-up prior to removing the patch
One day of DOIs is planned for this trial. Subjects will ingest tablets per the dosing 
outlined in Table 8-1 below. For subjects in Cohort 2, site staff will confirm that subjects 
did not take their prescribed dose of aripiprazole at home prior to the DOI of Abilify 
MyCite. Subjects will ingest tablets with approximately 60 mL of bottled water. The 
tablets will be administered by research staff and staff members will observe and record 
the timing of the individual ingestion events on the DOI eCRF. Site staff will conduct 
mouth checks and also verify cheeking after a subject swallows each tablet. 
Table 8-1
Dosing Schedule
Cohort
Ingestions/Session
Time Between Dosing Sessions 
(minutes)
Visit
Cohort 1 
One IEM tablet (MIT dose form) / 
15 times
Approximately every 
15 (−5 / +15) minutes 
2
Cohort 2 
Single dose of Abilify MyCite / 1 time
Not applicable
2
For any subject where tablet registration is missing, the trial team will consider execution 
of additional trial parameters including, but not limited to the following: ruling out bad 
patch impedance (eg, patch is not adhering to the skin properly) that can be addressed by 
changing the patch, potential contamination of the placebo tablets by introducing a new, 
sealed bottle of placebo tablets, and removing the DMS from the patient and having a 
non-site related, sponsor representative test the system independent of the subject to rule 
out unexplained subject anomalies (eg, medical or unknown conditions that may prevent 
patch registration of the ingested tablet). Any parameters executed may necessitate 
additional subject enrollment to replace missing ingestions during trial testing.
Subjects will be sent home with a Sleep Diary to complete each day until they return for 
the follow-up visit on Day 8 [+ 2 days]. Instructions on how to complete the sleep diary 
will be provided to the subject by the trial staff. 
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Follow-up Visit
All patches will be removed by trial staff at the in-person follow-up visit if the patch is 
still adhered on Day 8 [+ 2 days]. Any patch that peels off during the trial should be 
retained by the subject and given to trial staff during the scheduled in-person follow-up 
visit. If an in-person follow-up visit cannot occur, the site should conduct a telephone 
follow-up visit to assess safety and instruct the subject to remove the patch on Day 8. If 
the in-person follow-up visit is delayed past Day 8, subjects should be instructed to 
remove the patch on Day 8 and retain the patch to be given to site staff the in-person 
follow-up visit.
Subjects will return the completed Sleep Diary to trial staff at this visit. 
At the in-person safety follow-up visit, information regarding AEs that may have 
occurred during or since Visit 2 will be elicited. Any ongoing AE associated with the use 
of the device or IEMs at the in-person follow-up visit should be followed to resolution 
per the judgment of the investigator unless the subject is lost to follow-up. If an in-person 
follow-up visit cannot occur, the site should conduct a telephone follow-up visit and 
verbally assess subject safety.
Responsibilities for Testing Subjects
•
Wear the D-Tect Patch on the torso during the Testing Day and leave the patch on the 
torso until the in-person follow-up visit or the patch falls off. 
•
Complete a Sleep Diary each day until the in-person follow-up visit.
•
Direct observed ingestions:

Cohort 1: Swallow 15 MITs in a single calendar day.

Cohort 2: Swallow a single dose of Abilify MyCite in a single calendar day at the 
same dose as subject’s aripiprazole prescription.
•
Subjects must be comfortable reporting any AEs (Section 8.7).
•
Participate in all onsite visits and procedures.
•
Participate in an in-person safety follow-up site visit approximately 7 days (+ 2 days) 
after applying the D-Tect Patch. All patches will remain on the torso until removed 
by trial staff at the in-person follow-up visit on Day 8. If a patch falls of early, the 
subject should retain the patch and return it to site staff at their scheduled in-person 
follow-up visit. 
8.1
Efficacy Assessments
Not applicable. 
8.2
Pharmacokinetic Assessments
Not applicable.
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8.3
Biomarker Assessments
8.3.1
Pharmacodynamic Assessments
Not applicable.
8.4
Pharmacogenomic Assessments
Not applicable.
8.5
Future Biospecimen Research Samples
Not applicable.
8.6
Safety Assessments
Reporting of AEs associated with the use of the device or ingestion of IEMs (MITs or 
Abilify MyCite) will occur during active testing participation. AEs will be triaged and 
assessed as appropriate (Section 8.7). 
Details pertaining to the definitions, collection, reporting, and follow-up of AEs are 
described in Section 8.7.
8.6.1
Skin Irritation Scoring System
If an AE is related to the patch, then the Skin Irritation Scoring System (Table 8.6.1-1) 
will be completed by the investigator.1 A photo of the affected area should also be taken. 
Patch-related AEs Grade 2 or above will be considered clinically significant for purposes 
of this trial and must be recorded on the safety reporting form and on the eCRF.
Table 8.6.1-1
Skin Irritation Scoring System
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: United States (US) Department of Health and Human Services, Food and Drug Administration 
Center for Drug Evaluation and Research, December 1999.1
8.6.2
Clinical Laboratory Assessments
Not applicable.
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8.6.3
Physical Examination
A physical examination is not required to be performed as part of screening, although 
evaluation of any subsequent AEs may require a targeted exam by a member of the 
clinical staff.
8.6.4
Vital Signs
Vital signs will be collected at the time point described in the schedule of assessments 
(Section 1.3). Subject vital signs should be monitored and assessed for potential clinical 
significance. 
8.6.5
Electrocardiogram
Not applicable.
8.7
Adverse Events
8.7.1
Definitions
•
Adverse Event (AE): any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) in subjects, users 
or other persons, whether or not related to the investigational medical device or IEMs 
(MITs and/or Abilify MyCite) and whether anticipated or unanticipated.2
•
Serious adverse event (SAE): AE that led to any of the following:

Death

Serious deterioration in the health of the subject, users, or other persons as 
defined by one or more of the following:
•
A life-threatening illness or injury
•
A permanent impairment of a body structure or a body function including 
chronic diseases
•
Inpatient or prolonged hospitalization

Planned hospitalization for a pre-existing condition, or a procedure 
required by the clinical investigation plan, without serious deterioration in 
health, is not considered an SAE
•
Medical or surgical intervention to prevent life-threatening illness or injury, or 
permanent impairment to a body structure or a body function

Fetal distress, fetal death, a congenital abnormality, or birth defect including 
physical or mental impairment

Nonserious AEs: all AEs that do not meet the definition of an SAE are considered 
nonserious AEs.
•
Immediately Reportable Event (IRE):

Any SAE.
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Severity: Adverse events will be graded on a 3-point scale and reported as indicated in 
the eCRF. The severity of an adverse experience is defined as follows:
1 = Mild:
Discomfort noticed, but no disruption to daily activity.
2 = Moderate:
Discomfort sufficient to reduce or affect normal daily activity.
3 = Severe:
Inability to work or perform normal daily activity.
Causality: Assessment of causal relationship of an AE to the use of the patch, MITs, 
and/or Abilify MyCite is defined as follows:
Related: 
There is a reasonable possibility of a temporal and causal 
relationship between the patch, MITs, and/or Abilify MyCite and 
the AE.
Not Related: 
There is no temporal or causal relationship between the patch, 
MITs, and/or Abilify MyCite and the AE.
8.7.2
Eliciting and Reporting Adverse Events
The investigator will periodically assess subjects for the occurrence of AEs (serious and 
nonserious, associated with the use of the patch, MITs, and/or Abilify MyCite) from the 
time the ICF is signed until the end of the trial. For this trial, information on AEs will be 
followed until resolution as determined by the investigator. All patches will be removed 
by trial staff at the in-person follow-up visit. Any patch that peels off during the trial 
should be retained by the subject and given to trial staff at the scheduled in-person 
follow-up visit. 
To avoid bias in eliciting AEs, subjects should be asked the nonleading question: “How 
have you felt since your last visit?” All AEs (serious and nonserious) must be collected. 
All SAEs must be reported within 24 hours of awareness, no later than 72 hours in the 
case of a weekend or holiday. If a patch-related AE is reported by the subject, it will be 
graded per Section 8.6.1. A full list of all reported events will be kept by the clinical 
research site.
For this trial, all IREs (SAEs) detected during the program must be reported to:
•
Global_intake@otsuka-us.com
•
(fax) 301-212-8626
Reconciliation of AEs reported in this trial will be performed at the end of the trial.
8.7.3
Immediately Reportable Events
The investigator must immediately report (within 24 hours), using an IRE form, after 
he/she or site personnel become aware of any IRE (SAE), by telephone, fax, or e-mail to 
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the sponsor or designee using the contact information on the cover page of this protocol 
(please note that the IRE form is NOT the AE eCRF). Patient confidentiality must be 
protected and contact information such as name, address, phone number or any other 
protected health information as determined by applicable local regulation must be 
redacted when forwarding Safety Information and supporting documentation. Details 
regarding the follow-up of IREs are included in Section 8.7.7.2.
8.7.4
Medical Device Incidents (Including Malfunctions)
Not applicable. 
8.7.5
Adverse Events of Special Interest
Not applicable.
8.7.6
Procedure for Breaking the Blind
This trial does not use blinding procedures.
8.7.7
Follow-up of Adverse Events
8.7.7.1
Follow-up of Nonserious Adverse Events
Nonserious AEs that are identified at any time during the trial must be recorded on the 
AE eCRF with the current status (ongoing or resolved/recovered) noted. All nonserious 
events (that are not IREs) that are ongoing at the last scheduled contact will be recorded 
as ongoing in the eCRF. For any AE having been identified throughout the trial, or during 
analysis, additional relevant medical history information may be requested by the sponsor 
to further ascertain causality (including, but not limited to, information such as 
risk-related behavior, family history, and occupation).
8.7.7.2
Follow-up of Immediately Reportable Events and Serious 
Adverse Events 
This trial requires that subjects be actively monitored for IREs (SAEs) up to 7 days (+2 
days) after applying the D-Tect Patch and DOIs.
Immediately reportable events that are identified or ongoing at the last scheduled 
contact must be recorded as such on the AE eCRF page and the IRE form. If updated 
information (eg, resolved status) on IRE status becomes available after a subject’s last 
scheduled contact (up to the last in-clinic visit for the entire trial), this must be reported to 
the sponsor and recorded on the AE eCRF page and the IRE form, according to the 
appropriate reporting procedures described in Section 8.7.3.
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It is expected that the investigator will provide or arrange appropriate supportive care for 
the subject and will provide prompt updates on the subject’s status to the sponsor. The 
investigator will follow the IREs until:
•
the events are resolved,
•
the events have stabilized,
•
the subject is lost to follow-up, or
•
the subject has died.
Resolution means that the subject has returned to the baseline state of health and 
stabilized means that the investigator does not expect any further improvement or 
worsening of the subject’s condition. The investigator will continue to report any 
significant follow-up information to the sponsor up to the point the event has resolved or 
stabilized, or the subject is lost to follow-up, or has died.
8.7.7.3
Follow-up and Reporting of Immediately Reportable Events 
Occurring After Last Scheduled Contact 
Any new IREs (SAEs) reported to the investigator which occur after the last scheduled 
contact and are determined by the investigator to be reasonably associated with the use of 
the trial intervention(s), should be reported to the sponsor according to the procedures 
outlined in Section 8.7.3. This may include IREs that are captured on follow-up telephone 
contact or at any other time point after the defined trial period. Any significant follow-up 
information should continue to be reported to the sponsor until the events are resolved or 
stabilized, or the subject is lost to follow-up or has died.
8.8
Treatment of Overdose
For this trial, any dose of Abilify MyCite that is greater than the planned dose level (ie, 
subjects are planned to ingest Abilify MyCite at the same dose as their currently 
prescribed aripiprazole) will be considered an overdose for Cohort 2. In the event of an 
overdose, refer to the Abilify MyCite USPI for management of overdosage. To mitigate 
the risk of potential overdose, site staff will confirm that subjects do not take their 
prescribed dose of aripiprazole at home prior to the DOI of Abilify MyCite.
8.9
Subject Assessment Recording
Not applicable.
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8.10
Other Assessments
8.10.1
Positive Detection Accuracy
The number of total DOIs will be reported by the site on the eCRF. Positive detections 
will be downloaded from the trial mobile device(s) for analysis. 
8.10.2
Detection Latency Measures 
The DOI time will be recorded in the eCRF to the nearest minute by the site. Signal 
detection times will be downloaded from the trial mobile device(s) for analysis. 
8.10.3
Sleep Diary
On Day 1 of the trial, subjects will be sent home with a sleep diary to complete each day 
until they return for the follow-up visit on Day 8 [+ 2 days]. Instructions on how to 
complete the sleep diary will be provided to the subject by the trial staff. The sleep diary 
responses will be reported by the site on the eCRF. 
9
Statistical Considerations
9.1
Sample Size
For Cohort 1, a minimum of 24 subjects are planned to complete 15 DOIs per subject. 
With this assumption, 24 subjects with 360 ingestions will provide sufficient power to 
ensure the lower bound of the 95% confidence interval (CI) for PDA is at 95% assuming 
the PDA rate of 97.3% of the D-Tect Patch using binomial distribution. 
For Cohort 2, there is no formal sample size calculation. A minimum of 30 subjects are 
planned to complete a single DOI of Abilify MyCite.
9.2
Datasets for Analysis
The following analysis samples are defined for this trial:
•
Enrolled Sample: all subjects who sign an ICF and enter the trial (and only subjects 
who meet all the inclusion criteria and none of the exclusion criteria).
•
The intent-to-treat (ITT) population: ITT population consists of all subjects who took 
at least 1 dose of MITs or Abilify MyCite.
•
Safety Sample: all subjects who wear any patch or take any tablet from the trial and 
have any safety assessment.
9.3
Handling of Missing Data for Primary and Secondary Endpoint 
Analysis
Missing data on PDA and/or detection latency measures will not be imputed. 
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9.4
Statistical Analyses
9.4.1
Primary Endpoints
The number of positive detections and PDA will be summarized for the D-Tect Patch for 
Cohort 1; the 95% CI of PDA will be provided using the Clopper-Pearson method. PDA 
is defined as PDA = k  n, where n is the number of the total DOIs, and k is the number 
of positive detections by the patch. 
For detection latency, summary statistics will be provided for Patch Detection Latency, 
Ingestion Data Transfer Latency, and Total Detection Latency. Kaplan-Meier curves will 
be plotted for all of the latency times.
9.4.2
Secondary Endpoint
The frequency and severity of AEs, device-related AEs, SAEs, AEs leading to 
discontinuation, and unanticipated adverse device effects will be summarized. 
9.4.2.1
Adverse Events
All AEs will be coded by system organ class and Medical Dictionary for Regulatory 
Activities (MedDRA) preferred term. The incidence of the following events will be 
summarized:
•
AEs
•
AEs by severity
•
AEs potentially causally related to the investigational device
•
AEs with an outcome of death
•
SAEs
•
AEs leading to discontinuation of the investigational device
9.4.2.2
Clinical Laboratory Data
Not applicable. 
9.4.2.3
Physical Examination and Vital Signs Data
Baseline vital signs data will be provided in a listing.
9.4.2.4
Electrocardiogram Data
Not applicable. 
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9.4.3
Other Analyses
9.4.3.1
Analysis of Demographic and Baseline Characteristics
Baseline demographic characteristics including age, race, ethnicity, sex at birth, gender, 
etc, will be summarized by cohort using descriptive statistics. Summary statistics will 
consist of mean, median, minimum, maximum, and standard deviation for continuous 
variables and tabulations of frequency distributions for categorical variables.
9.5
Interim Analysis 
No interim analysis or adaptive design are applicable.
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10
Supporting Documentation and Operational Considerations
10.1
Appendix 1: Regulatory, Ethical, and Trial Oversight 
Considerations
10.1.1
Ethics and Responsibility
This trial must be conducted in compliance with the protocol, FDA regulations, 
applicable ICH (International Council for Harmonisation) GCP guidance, international 
ethical principles derived from the Declaration of Helsinki and Council for International 
Organizations of Medical Science (CIOMS) guidelines, and applicable local laws and 
regulations. Each trial site will seek approval/favorable opinion by an IRB according to 
regional requirements, and the investigator will provide that documentation to the 
sponsor. The IRB will evaluate the ethical, scientific, and medical appropriateness of the 
trial. Further, in preparing and handling the eCRF and any safety information, the 
investigator, subinvestigator, and their staff will take measures to ensure adequate care in 
protecting subject privacy. To this end, a subject ID will be used to identify each subject.
Financial aspects, subject insurance, and the publication policy for the trial will be 
documented in the agreement between the sponsor and the investigator.
10.1.2
Informed Consent
Informed consent will be freely obtained from all subjects (or their guardian or legally 
acceptable representative, as applicable for local laws). The ICF will be approved by the 
same IRB that approves this protocol. 
Each ICF will comply with the ICH GCP Guidelines and local regulatory requirements. 
The investigator will ensure that the sponsor reviews and authorizes any written 
site-specific ICF used in the trial before submission to the IRB. 
Investigators may discuss trial availability and the possibility for entry with a potential 
subject without first obtaining consent. However, informed consent must be obtained and 
documented before initiation of any procedures that are performed solely for the purpose 
of determining eligibility for this trial, including withdrawal from current medication(s). 
Potential subjects are free to refuse entry into the trial, or withdraw from the trial at any 
time, without justification, and there will be no consequences to their further care.
Once appropriate essential information has been provided and fully explained in 
layman’s language to the subject by the investigator (or a qualified designee), and it has 
been documented that the subject has had the opportunity to ask questions and have those 
questions answered, the IRB-approved paper ICF will be signed and dated by both the 
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subject and the person obtaining consent (investigator or designee), as well as by any 
other parties required by the IRB. The subject will receive a copy of the signed ICF; the 
original shall be kept on file by the investigator. 
Subjects may be asked to sign additional ICFs if the protocol is amended and the changes 
to the protocol result in additional information that needs to be provided to the subjects, 
so that they can make a knowledgeable and voluntary decision on continued trial 
participation. Female partners of male subjects who become pregnant during the course 
of the trial may be asked to sign additional ICFs in order to collect additional information 
regarding the nonsubject partner and fetus.
10.1.3
Recruitment Strategy
Subjects may be recruited through several sources, including but not limited to the site 
database and advertising in traditional or online media. 
10.1.4
Confidentiality
All information generated in this trial will be considered confidential and will not be 
disclosed to anyone not directly concerned with the trial without the sponsor’s prior 
written permission. Subject confidentiality requirements of the region(s) where the trial is 
conducted will be met. However, authorized regulatory officials and sponsor personnel 
(or their representatives) may be allowed full access to inspect and copy the records, 
consistent with local requirements. All trial devices and/or other materials collected shall 
be used solely in accordance with this protocol, unless otherwise agreed to in writing by 
the sponsor.
Subjects will be identified only by unique subject ID in the eCRF. If further subject 
identification is required, subjects’ full names may be made known to a regulatory 
agency or other authorized officials, if necessary, subject to local regulations.
10.1.5
Quality Control and Quality Assurance
10.1.5.1
Monitoring
The sponsor has ethical, legal, and scientific obligations to follow this trial in accordance 
with established research principles, the applicable ICH GCP guidance, and applicable 
regulatory requirements and local laws. As part of a concerted effort to fulfill these 
obligations (maintain current personal knowledge of the progress of the trial), the 
sponsor’s monitors will visit the site during the trial, as well as communicate frequently 
via telephone, email, and written communications. In addition, all investigators and trial 
site personnel will undergo initial and ongoing training for this particular trial, and this 
training will be clearly documented.
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10.1.5.2
Auditing
The sponsor’s Quality Assurance Unit (or representative) may conduct trial site audits. 
Audits will include, but are not limited to, investigational device supply, presence of 
required documents, the informed consent process, site operations, delegation of 
authority and training, and a review of the eCRF with source documents, as applicable. 
The investigator will agree to cooperate and participate with audits.
Regulatory authorities may inspect the investigator site during or after the trial. The 
investigator will cooperate with such inspections and will contact the sponsor 
immediately if such an inspection occurs.
10.1.6
Protocol Deviations
In the event of a significant/major deviation from the protocol due to an emergency, 
accident, or mistake (eg, violation of informed consent process, trial device dispensing or 
subject dosing error, subject enrolled in violation of eligibility criteria or concomitant 
medication criteria), the investigator or designee will contact the sponsor or designee at 
the earliest possible time by telephone or via email. The investigator and sponsor (or 
designee) will come as quickly as possible to a joint decision regarding the subject’s 
continuation in the trial. This decision will be documented by the investigator and the 
sponsor (or designee) and reviewed by the site monitor.
Any major protocol deviation will be recorded in the eCRF along with the start date and 
details of the deviation.
10.1.7
Records Management
10.1.7.1
Source Documents
Source documents are defined as the results of original observations and activities of a 
clinical investigation. Source documents will include but are not limited to medical 
records, electronic data, screening logs, progress notes, paper-based assessments and 
scales, and recorded data from automated instruments or applications. All source 
documents pertaining to this trial will be maintained by the investigators and made 
available for direct inspection by authorized persons.
Investigator(s)/institution(s) will permit trial-related monitoring, audits, IRB review, and 
regulatory inspection(s) by providing direct access to source data/documents by 
authorized persons as defined in the ICF. In all cases, subject confidentiality must be 
maintained in accordance with local regulatory requirements.
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10.1.7.2
Data Collection
During each subject’s visit to the site, an investigator or their designee participating in the 
trial will record information to document all significant observations. At a minimum, 
these notes will contain:
•
Documentation of the informed consent process, including any revised ICFs;
•
Documentation of the investigator’s decision to enroll the subject into the trial, the 
review of all inclusion/exclusion criteria prior to initiation of any trial procedures, and 
confirmation of the subject’s actual participation in the trial;
•
Documentation of baseline and demographic characteristics (eg, age, sex at birth, 
race, ethnicity);
•
The date of the visit and the corresponding Visit or Day in the trial schedule;
•
General subject status remarks, including any significant medical findings. The 
severity, frequency, duration, action taken, and outcome of any AEs and the 
investigator’s assessment of relationship to trial investigational device must also be 
recorded;
•
Any changes in concomitant medications or dosages;
•
A general reference to the procedures completed, including dosing and trial procedure 
compliance; 
•
The signature (or initials) and date of the investigator (or designee) who made an 
entry in the medical record.
In addition, any contact with the subject via telephone or other means that provides 
significant clinical information will also be documented in the progress notes as 
described above.
Information from medical records and other source documents will be entered by 
investigative site personnel onto eCRFs in the sponsor’s electronic data capture (EDC) 
system that is 21 Code of Federal Regulations (CFR) Part 11 compliant. Changes to the 
data will be captured by an automatic audit trail in the EDC system.
At the end of the trial, the investigator must certify that the data entered into the eCRF 
application are complete and accurate. After database lock, the investigator will receive 
an electronic copy of the subject data. 
10.1.7.3
File Management at the Trial Site
The investigator will ensure that the trial site file is maintained in accordance with 
applicable ICH GCP guidance and as required by applicable local regulations. The 
investigator/institution will take measures to prevent accidental or premature destruction 
of these documents.
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10.1.7.4
Records Retention at the Trial Site
The FDA regulations require all investigators participating in clinical drug studies to 
maintain detailed clinical data for one of the following periods:
•
A period of at least 2 years after the date on which a New Drug Application is 
approved by the FDA;
•
A period of 2 years after the sponsor has notified the FDA that investigation with this 
drug is discontinued.
The investigator must not dispose of any records relevant to this trial without either 
(1) written permission from the sponsor or (2) provision of an opportunity for the sponsor 
to collect such records. The investigator will be responsible to maintain adequate and 
accurate electronic or hard copy source documents of all observations and data generated 
during this trial including any data clarification forms received from the sponsor. Such 
documentation is subject to inspection by the sponsor and relevant regulatory authorities. 
If the investigator withdraws from the trial (eg, due to relocation or retirement), all 
trial-related records should be transferred to a mutually agreed-upon designee within a 
sponsor-specified timeframe. Notice of such transfer will be given to the sponsor in 
writing.
10.1.7.5
Dissemination of Clinical Trial Data
Not applicable. 
10.1.7.6
Publication Authorship Requirements
Authorship for any Otsuka-sponsored publications resulting from the conduct of this trial 
will be based on International Committee of Medical Journal Editors (ICMJE) authorship 
criteria (http://www.icmje.org/recommendations). According to ICMJE guidelines, one 
may be considered an author only if the following criteria are met:
1) Substantial contributions to the conception or design of the work; or the 
acquisition, analysis, or interpretation of data for the work; AND
2) Drafting the work or revising it critically for important intellectual content; AND
3) Final approval of the version to be published; AND
4) Agreement to be accountable for all aspects of the work in ensuring that questions 
related to the accuracy or integrity of any part of the work are appropriately 
investigated and resolved.
All authors must meet the above criteria, and all who qualify for authorship based on the 
above criteria should be listed as authors.
Investigators or other personnel involved in the conduct of the trial who do not qualify 
for authorship may be acknowledged in publications resulting from the trial. By agreeing 
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to participate in the trial, investigators or other personnel involved in the conduct of the 
trial consent to such acknowledgement in any publications resulting from its conduct.
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10.2
Appendix 2: Contraceptive Guidance and Collection of Pregnancy 
Information
Females of childbearing potential (FOCBP) are females whose menstruation has started 
and who are not documented as sterile (eg, have had a bilateral oophorectomy, or 
hysterectomy, or who have been postmenopausal for at least 12 months). Females of 
non-childbearing potential do not meet definition of FOCBP.
Any subject that is currently pregnant or planning to become pregnant at the time of trial 
start is not eligible for participation. Females of childbearing potential are required to 
have a negative urine pregnancy test during screening. Subjects prescribed and taking 
aripiprazole should consult with their prescribing physicians regarding contraceptive 
recommendations with respect to family planning. 
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10.3
Appendix 3: Protocol Amendments
The investigator will not make any changes to this protocol without the sponsor’s prior 
written consent and subsequent approval/favorable opinion by the IRB. Any permanent 
change to the protocol, whether an overall change or a change for specific trial site(s), 
must be handled as a protocol amendment. Any amendment will be written by the 
sponsor. Each amendment will be submitted to the IRB, as required by local regulations. 
Except for “administrative” or “non-substantial” amendments, investigators will wait for 
IRB approval/favorable opinion of the amended protocol before implementing the 
change(s). Non-substantial amendments are defined as having no effect on the safety of 
subjects, conduct or management of the trial, trial design, or the quality or safety of 
intervention(s) used in the trial. A protocol change intended to eliminate an apparent 
immediate hazard to subjects should be implemented immediately after agreement by the 
sponsor and investigator, followed by IRB notification within local applicable timelines. 
The sponsor will submit protocol amendments to the applicable regulatory agencies 
within local applicable timelines.
When the IRB , investigators, and/or the sponsor conclude that the protocol amendment 
substantially alters the trial design and/or increases the potential risk to the subject, the 
currently approved written ICF will require similar modification. In such cases, after 
approval/favorable opinion of the new ICF by the IRB, repeat written informed consent 
will be obtained from currently enrolled subjects in the trial before the amendment-
specified changes in the trial are implemented.
10.3.1
Protocol Amendment(s)
Not applicable.
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Agreement
I, the undersigned principal investigator, have read and understand the protocol (including the 
Investigator’s Brochure) and agree that it contains all the ethical, legal and scientific information 
necessary to conduct this trial in accordance with the principles of Good Clinical Practices and as 
described herein and in the sponsor’s (or designee’s) Clinical Trial Agreement.
I will provide copies of the protocol to all physicians, nurses, and other professional personnel to 
whom I delegate trial responsibilities. I will discuss the protocol with them to ensure that they are 
sufficiently informed regarding the investigational device, D-Tect Patch and ingestible event markers, 
the concurrent medications, the efficacy and safety parameters and the conduct of the trial in general. I 
am aware that this protocol must be approved by the Institutional Review Board (IRB) responsible for 
such matters in the clinical trial facility where the D-Tect Patch and ingestible event markers will be 
tested prior to commencement of this trial. I agree to adhere strictly to the attached protocol (unless 
amended in the manner set forth in the sponsor’s Clinical Trial Agreement, at which time I agree to 
adhere strictly to the protocol as amended).
I understand that this IRB-approved protocol will be submitted to the appropriate regulatory 
authority/ies by the sponsor. I agree that clinical data entered on eCRF by me and my staff will be 
utilized by the sponsor in various ways, such as for submission to governmental regulatory authorities 
and/or in combination with clinical data gathered from other research sites, whenever applicable. I 
agree to allow sponsor and designee monitors and auditors full access to all medical records at the 
research facility for subjects screened or enrolled in the trial.
I agree to await IRB approval before implementation of any substantial amendments to this protocol. 
If, however, there is an immediate hazard to subjects, I will implement the amendment immediately, 
and provide the information to the IRB within the required local applicable timelines. Administrative 
changes to the protocol will be transmitted to the IRB for informational purposes only, if required by 
local regulations.
I agree to provide all subjects with informed consent forms, as required by the applicable regulations 
and by ICH guidelines. I agree to report to the sponsor any adverse experiences in accordance with the 
terms of the sponsor’s Clinical Trial Agreement and the relevant regional regulation(s) and 
guideline(s). I further agree to provide all required information regarding financial certification or 
disclosure to the sponsor for all investigators and subinvestigators in accordance with the terms of the 
relevant regional regulation(s). I understand that participation in the protocol involves a commitment 
to publish the data from this trial in a cooperative publication before publication of efficacy and safety 
results on an individual basis may occur, and I consent to be acknowledged in any such cooperative 
publications that result.
____________________________
_____________________________
___________
Principal Investigator Print Name
Signature
Date
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SAP_001.pdf: 
Statistical Analysis Plan (SAP) 
Version Date: 22-JUN-2023 
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Protocol No: 031-201-00521
Page 1 of 20
Strictly Confidential.  © 2023, PRA Health Sciences.  All rights reserved.
Statistical Analysis Plan (SAP)
Protocol Title:
An Open-label, Prospective Trial Assessing Positive Detection 
Accuracy and Detection Latency Measures of the Miniature 
Ingestible Event Marker Tablet Using the D-Tect Patch in 
Healthy Subjects and Assessing Detection Latency Measures 
Using the D-Tect Patch in Subjects With Serious Mental 
Illness Taking Abilify MyCite Tablet
Protocol Version No./Date:
1.0/18-APR-2023
CRF Version No./Date:
1.3/02-JUN-2023
SAP Version No./Date:
1.0/22-JUN-2023
1.0 Approvals
Sponsor
Sponsor Name:
Otsuka Pharmaceutical Development & Commercialization, Inc.
Representative/ Title:
/ Director, Global Clinical Development
Signature /Date:
Representative/ Title:
 / Senior Director, Head of Biostatistics
Signature /Date:
Representative/ Title:
 / Biostatistics Lead for Digital Medicine (Abilify MyCite)
Signature /Date:
ICON
Biostatistician / Title:
 / Senior Biostatistician
Signature /Date:
(NOTE: Electronic Signatures should only be used if all parties have the ability to eSign.)
Synopsis Clinical Study Report  031-201-00521
4.1.5 Documentation of Statistical Methods
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Statistical Analysis Plan (SAP) 
Version Date: 22-JUN-2023 
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Protocol No: 031-201-00521
Page 2 of 20
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2.0 Change History
Version/Date
Change Log
1.0
Final Version 1.0
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Statistical Analysis Plan (SAP) 
Version Date: 22-JUN-2023 
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Protocol No: 031-201-00521
Page 3 of 20
Strictly Confidential.  © 2023, PRA Health Sciences.  All rights reserved.
3.0 Table of Contents
1.0 Approvals...................................................................................................................................1
2.0 Change History ..........................................................................................................................2
3.0 Table of Contents.......................................................................................................................3
4.0 Purpose ......................................................................................................................................5
5.0 Scope..........................................................................................................................................5
6.0 Introduction................................................................................................................................5
6.1 Changes from Protocol........................................................................................................5
7.0 Study Objectives........................................................................................................................5
7.1 Primary Objective ...............................................................................................................5
7.2 Secondary Objective ...........................................................................................................5
8.0 Study Design..............................................................................................................................5
8.1 Sample Size Considerations................................................................................................7
8.2 Randomization ....................................................................................................................8
9.0 Study Estimands ........................................................................................................................8
9.1 Endpoints ............................................................................................................................8
9.2 Population Sets....................................................................................................................8
9.2.1 Screened Analysis Set ...............................................................................................8
9.2.2 Enrolled Analysis Set ................................................................................................8
9.2.3 Full Analysis Set........................................................................................................9
9.2.4 Safety Analysis Set....................................................................................................9
9.2.5 Summary of Analysis Sets.........................................................................................9
10.0 Conventions and Derivations.................................................................................................10
10.1 Visit Windows.................................................................................................................10
10.2 Unscheduled Visit Definition..........................................................................................10
10.3 Prior and Concomitant Medication.................................................................................10
10.4 Definition of Body Mass Index.......................................................................................10
10.5 Definition of Treatment-Emergent Adverse Event.........................................................11
10.6 Definition of Positive Detection Accuracy .....................................................................11
10.7 Definition of Detection Latency......................................................................................11
10.8 Missing Data ...................................................................................................................12
11.0 Interim Analyses....................................................................................................................12
12.0 Statistical Methods.................................................................................................................12
12.1 Subject Disposition .........................................................................................................12
12.2 Demographic and Baseline Characteristics.....................................................................14
12.2.1 Medical History.....................................................................................................14
12.2.2 Prior and Concomitant Medications......................................................................14
12.3 Device Application..........................................................................................................15
12.3.1 Directly Observed Ingestion..................................................................................15
12.3.2 Drug Exposure.......................................................................................................15
12.3.3 Patch Application and Removal ............................................................................16
12.4 Protocol Deviations.........................................................................................................17
12.5 Primary Analyses ............................................................................................................17
12.5.1 Positive Detection Accuracy .................................................................................17
12.5.2 Detection Latency Measures .................................................................................17
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Statistical Analysis Plan (SAP) 
Version Date: 22-JUN-2023 
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Protocol No: 031-201-00521
Page 4 of 20
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12.6 Safety Analyses...............................................................................................................17
12.6.1 Treatment-Emergent Adverse Events....................................................................17
12.6.2 Deaths and Serious TEAEs ...................................................................................18
12.6.3 Laboratory Data.....................................................................................................19
12.6.4 Vital Signs .............................................................................................................19
13.0 Glossary of Abbreviations .....................................................................................................19
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Statistical Analysis Plan (SAP) 
Version Date: 22-JUN-2023 
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Protocol No: 031-201-00521
Page 5 of 20
Strictly Confidential.  © 2023, PRA Health Sciences.  All rights reserved.
4.0 Purpose
The Statistical Analysis Plan (SAP) describes the statistical methods to be used during the 
reporting and analyses of data collected under Otsuka Pharmaceutical Development & 
Commercialization, Inc’s Protocol  031-201-00521 dated 18-APR-2023.
5.0 Scope
The Statistical Analysis Plan outlines the following:
•
Study Objectives
•
Study Design
•
Applicable Study Definitions
•
Statistical Methods
6.0 Introduction
This SAP should be read in conjunction with the study protocol and case report form (CRF). Any 
further changes to the protocol or CRF may necessitate updates to the SAP.
6.1 Changes from Protocol
There are no major discrepancies between protocol and SAP, only the following minor differences 
are described:
1. Population definitions (SCR, FAS, FAS-Cohort 1, and FAS-Cohort 2) added, the protocol 
specified the intent-to-treat population, however, the full analysis set will be used.
2. The unanticipated adverse device effects stated in the protocol removed from the analysis.
3. AEs leading to discontinuation of the investigational device removed from analysis, instead 
AEs leading to study discontinuation will be analyzed.
7.0 Study Objectives
7.1 Primary Objective
The primary objectives of this study are:
•
To evaluate positive detection accuracy (PDA) for the D-Tect Patch. 
•
To evaluate detection latency measures for the D-Tect Patch.
7.2 Secondary Objective
The secondary objective of this study is to collect and characterize AEs associated with the device.
8.0 Study Design
This two-cohort, open-label, prospective trial is designed to assess the PDA and detection latency 
of the D-Tect Patch. The PDA is defined as the proportion of miniature ingestible event marker 
tablets (MITs) detected out of the total ingestible event marker (IEM) detections of tested D-Tect 
Patches (Cohort 1 only). For detection latency, Patch Detection Latency, Ingestion Data Transfer 
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Statistical Analysis Plan (SAP) 
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Protocol No: 031-201-00521
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Latency, and Total Detection Latency will be measured for both cohorts (i.e., MITs and Abilify 
MyCite). 
Cohort 1 will be completed in adult, healthy subjects. Subjects with difficulty swallowing, active 
skin infection or history of inflammatory skin condition, or an allergy to adhesive bandages/tapes 
will be excluded from participation. Subjects in Cohort 1 will take the MIT dose form. A minimum 
of 24 healthy subjects will be tested to obtain a minimum of 360 miniature ingestible event marker 
tablet ingestions for Cohort 1. This trial will consist of up to 3 onsite visits including:
•
Visit 1: Screening
•
Visit 2 (Day 1): Testing, patch placement, directly observed ingestion (DOI) of MITs
(conducted either on the same day as Visit 1 or up to 7 days after Visit 1)
•
Visit 3 (Day 8): In-person safety follow-up and removal of patch (conducted approximately
7 days [+ 2 days] after applying the D-Tect Patch).
Cohort 2 will be completed in adults with serious mental illness (SMI) who are prescribed and 
taking aripiprazole prior to trial entry. Subjects with difficulty swallowing, active skin infection or 
history of inflammatory skin condition, or an allergy to adhesive bandages/tapes will be excluded 
from participation. Subjects will take a single dose of Abilify MyCite at the same dose as the 
subject’s current aripiprazole prescription. Subjects will be instructed not to take their currently 
prescribed dose of aripiprazole at home on Day 1 of the trial when Abilify MyCite will be ingested. 
A minimum of 30 subjects with SMI will be tested to obtain a minimum of 30 Abilify MyCite 
ingestions for Cohort 2. This trial will consist of up to 3 onsite visits including:
•
Visit 1: Screening
•
Visit 2 (Day 1): Testing, patch placement, DOI of a single dose of Abilify MyCite
(conducted either on the same day as Visit 1 or up to 7 days after Visit 1)
•
Visit 3 (Day 8): In-person safety follow-up and patch removal (approximately 7 days [+ 2
days] after applying the D-Tect Patch)
No trial procedures may be conducted prior to the signing of the informed consent form (ICF), 
which will occur at Visit 1. Visit 2 involves patch application and DOI(s). Visits 1 and 2 may be 
combined and conducted on the same day. Subjects will return to the site on Day 8 (+ 2 days), 7 
days following patch placement for a safety follow-up evaluation and to make final observations 
of patch wear (Visit 3). Any patches that remain on the subject will be removed at this visit. Any 
patch that falls off prior to the safety follow-up visit should be retained by the subject and given 
to trial staff at the scheduled follow-up visit. A full Schedule of Assessments is included in Table 
1.
Table 1: Schedule of Assessments (Cohorts 1 and 2)
Period
Screening
Testing 
Follow-up
Visit
Visit 1
Visit 2 a
Visit 3 b,c
Trial Day
Day −7 to Day 1
Day 1
Day 8 (+2 
days)
Informed Consent
X
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Statistical Analysis Plan (SAP) 
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Protocol No: 031-201-00521
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Demographics
X
Medical History
X
Concomitant Medications 
X
X
X
Eligibility Criteria Review
X
Vital Sign Measurements d
X
Preparation of application 
site and patch placement
X
Assessment of AEs e 
X
X
X
Photograph of patches at 
application site f 
X
X
DOI g,h
X
Sleep Diary i
X
Patch Removal j
X
Pregnancy Test k
X
Abbreviations:
AE = adverse event; DOI = directly observed ingestion.
Footnotes:
a Conducted either on the same day as Visit 1, or up to 7 days after Visit 1. 
b In-person safety follow-up to occur 7 days after applying the patch.
c If an in-person follow-up visit cannot occur due to COVID-19 restrictions, the site should conduct a follow-up visit via video 
conference to verbally assess subject safety and instruct the subject to remove the patch on Day 8.
d Vital sign measurements include blood pressure, heart rate, temperature, height, and weight. 
e If an AE is related to the patch, then the Skin Irritation Scoring System (Table 8.6.1-1) will be completed by the investigator.
f A minimum of 3 patch placement photos are required: prior to initial dose, after completion of DOI(s), and when the subject 
returns for follow-up (prior to patch removal).
g Cohort 1: Subjects will ingest 15 miniature ingestible event marker tablets (MITs) over the course of 1 visit day (with 
approximately 15 [−5 / +15] minutes between ingestions). 
h Cohort 2: Subjects will ingest a single dose of Abilify MyCite at the same dose as their currently prescribed aripiprazole.
i On Day 1 of the trial, subjects will be sent home with a sleep diary to complete each day until they return for the follow-up visit 
on Day 8 [+ 2 days].
j Any patch that falls off during the trial should be retained by the subject and given to trial staff during the in-person follow-up 
visit. All patches must be removed on Day 8, even if the clinic visit is delayed. 
k To be collected from woman of childbearing potential via urine dipstick.
8.1 Sample Size Considerations
The study is exploratory in nature, the sample size is not determined based on a specific hypothesis 
or effect size. 
For Cohort 1, a minimum of 24 subjects are planned to complete 15 DOIs per subject. With this 
assumption, 24 subjects with 360 ingestions will provide sufficient power to ensure the lower 
bound of the 95% confidence interval (CI) for PDA is at 95% assuming the PDA rate of 97.3% of 
the D-Tect Patch using binomial distribution.
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Statistical Analysis Plan (SAP) 
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For Cohort 2, there is no formal sample size calculation. A minimum of 30 subjects are planned to 
complete a single DOI of Abilify MyCite.
8.2 Randomization
Randomization is not applicable to this study.
9.0 Study Estimands
The ‘Estimands’ framework is used to define the treatment effect of interest in a clinical trial, 
which specifies how the treatment effect is to be estimated, and what assumptions are necessary 
to make the estimation valid. In this study, the treatment effect, as well as the potential sources of 
bias or variability that may impact the estimation of treatment effects, are not the research question 
of interest. The objective of this study is to assess the PDA and detection latency of the D-Tect 
Patch in an exploratory manner, therefore, the estimands in this study are not applicable.
9.1 Endpoints
Objectives
Endpoints
Primary
Primary endpoint for PDA
•
Estimate PDA with the CI lower limit greater 
than 95% when a subject is wearing the D-
Tect Patch.
Primary endpoint for Detection Latency
•
Evaluate PDA and detection latency 
measures for the D-Tect Patch.
•
The mean and median for three latency 
measures: Patch Detection Latency, Ingestion 
Data Transfer Latency, and Total Detection 
Latency (See Section 10.7 for detailed 
definition).
Secondary
Safety
•
To collect and characterize AEs 
associated with the device.
•
The frequency and severity of AEs, device-
related AEs, serious AEs (SAEs), and AEs 
leading to discontinuation
9.2 Population Sets
9.2.1 Screened Analysis Set
The Screened Analysis Set (SCR) will consist of all subjects who sign an ICF. This analysis set 
will be used to report disposition and screening failures.
9.2.2 Enrolled Analysis Set
The Enrolled Analysis Set (EAS) will consist of all subjects who sign an ICF and enter the trial 
(and only subjects who meet all the inclusion criteria and none of the exclusion criteria).
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9.2.3 Full Analysis Set
The Full Analysis Set (FAS) comprises all the detections of the wearable sensors done on the 
subjects who took at least 1 dose of MITs (Cohort 1) or Abilify MyCite (Cohort 2), excluding 
those detections with device malfunction (invalid session and impedance is bad).  
For the primary endpoint in Cohort 1, the FAS-Cohort 1 is a subset of the FAS and consists all 
the detections for subjects who took at least 1 dose of MITs (Cohort 1).
For the primary endpoint in Cohort 2, the FAS-Cohort 2 is a subset of the FAS and consists all 
the detections for subjects who took at least 1 dose of Abilify MyCite (Cohort 2).
9.2.4 Safety Analysis Set
The Safety Analysis Set (SAF) will consist of all subjects who wear any patch or take any tablet 
from the trial and have any safety assessment.
9.2.5 Summary of Analysis Sets
Analyses
SCR
EAS
FAS-Cohort 1
FAS-Cohort 2
SAF
Subject disposition
 
✓
Demographic and baseline 
characteristics
✓
Medical history
✓
Prior and concomitant medications
✓
Directly Observed Ingestion
✓
 ✓
Study Drug Exposure
✓
Patch Application and Removal
✓
✓
Protocol deviation
✓
Positive Detection Accuracy
✓
Detection Latency Measures
✓
✓
Adverse Events
✓
Treatment-Emergent Adverse Events 
(TEAEs)
✓
Deaths and Serious TEAEs
✓
Vital Signs
✓
Abbreviations:
SCR         = Screened Analysis Set,
EAS         = Enrolled Analysis Set,
FAS          = Full Analysis Set,
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Statistical Analysis Plan (SAP) 
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SAF         = Safety Analysis Set
10.0 Conventions and Derivations
10.1 Visit Windows
Table 2 shows study periods, visits, study days, and visit windows. The visit will be used for 
analysis according to the visit reported by the CRF.
Table 2: Study Visit Window
Study Period
Study Visit
Study Day
Study Visit Window
Eligibility screening 
Visit 1
-7 to 1
-
Testing 
Visit 2
1
-
Follow-up 
Visit 3
8
+ 2 days
Study day will be calculated as 
Study Day = Date of day – Date of Testing + 1
10.2 Unscheduled Visit Definition 
An Unscheduled Visit is defined as any additional visit performed at the investigator’s discretion, 
at any time between Testing (Day 1) and the Follow-Up Visit at Day 8.
10.3 Prior and Concomitant Medication
In this study, all medications and therapies taken by the subject from 7 days prior to D-Tect Patch 
application through the end of the evaluation period (defined as the time period during which 
subjects are evaluated for primary and/or secondary objectives) will be recorded. 
A medication is considered to be prior if the start date and time is before the first ingestion date 
and time. A medication is considered to be concomitant if the medication is ongoing at, started 
together with, or started after the first ingestion date and time. Note that a medication can be 
considered both prior and concomitant.
10.4 Definition of Body Mass Index
The BMI (Body Mass Index) calculation divides a subject’s weight in kilograms by their height in 
meters squared. The formula to calculate BMI is as follows:
BMI = weight (in kilograms) / (height (in meters))²
International System of Units for weight in kilogram (kg) and height in meter (m) will be used in 
analysis, the formulas for converting units of weight and height are as follows:
Weight in kilograms (kg) = Weight in pounds (lb) × 0.45359237
Height in meters (m) = Height in inches (in) × 0.0254
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10.5 Definition of Treatment-Emergent Adverse Event
TEAEs are defined as AEs that occurred on or after the subject wears any patch or takes any tablet 
from the trial at test day, and the AEs that occurred before the subject wears any patch or takes 
any tablet and are worsening, serious, related, or resulted in death, discontinuation, or interruption 
of investigational product. All other AEs recorded in CRF are considered Non-Treatment-
Emergent Adverse Events (Non-TEAEs).
10.6 Definition of Positive Detection Accuracy
The Positive Detection Accuracy (PDA) is defined as PDA = k/n, where n is the number of the 
total DOIs in FAS-Cohort 1 (malfunction sessions have been excluded from FAS-Cohort 1), 
and k is the number of total positive detections by the patch. 
10.7 Definition of Detection Latency
As shown in the system diagram in Figure 1, there are 4 time-stamped events (TSEs) associated 
with measuring detection latency shown in Table 3. 
Table 3: Time-stamped events (TSEs) associated with measuring detection latency
TSE 1
Subject takes tablet. Directly observed ingestion time is recorded by the clinician.
TSE 2
Tablet sends signal to the patch. Tablet is detected & recorded by the patch as an IEM 
record with a timestamp.
TSE 3
Patch sends ingestion data to phone. The tablet ingestion data is communicated to and 
recorded by the mobile device as a pill-ingestion-metric with a timestamp.
TSE 4
Tablet ingestion data is displayed. The tablet display event is triggered on the mobile 
device as a pill-display-event with a timestamp.
Figure 1: Digital Medicine System
The latency measurements between each of above timestamps are defined in Table 4.
Table 4: Latency measurements
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Latency Measurements
Definition
Maximum 
Observation 
Time
Patch Detection Latency
Time between TSE 1 and TSE 2 in 
seconds
10 minutes/600 seconds
Ingestion Data Transfer Latency
Time between TSE 2 and TSE 4 in 
seconds
5 minutes/300 seconds
Total Detection Latency
Time between TSE 1 and TSE 4 in 
seconds
15 minutes/900 seconds
For Kaplan-Meier estimate, if the DOI is successfully detected, it will be treated as positive 
detection and event = “1”; If the DOI is not successfully detected or latencies have been larger 
than the maximum observation time (defined above in Table 4), the data will be considered as 
censored data and event = “0”, where time to event is defined as maximum observation time.
10.8 Missing Data
All statistical analysis will be based on observed values. Missing values will not be imputed.
11.0 Interim Analyses
No interim analysis is planned in this study.
12.0 Statistical Methods
All analyses will use SAS® version 9.4 or higher. Table and listing outputs will be presented using 
ICON standard layouts. 
Unless specified otherwise, categorical variables will be summarized using counts and percentages 
(n [%]). Percentages will be rounded to one decimal place, except 100% will be displayed without 
any decimal places and percentages will not be displayed for zero counts. 
Continuous variables will be summarized using the number of observations (n), mean, and 
standard deviation, median, minimum, and maximum. The minimum, and maximum values will 
be displayed to the same level of precision as the raw data; the mean and the median to a further 
decimal place; and the standard deviation to two additional decimal places to a maximum of four.  
In listings, data will be presented with the same precision as the original data.
Unless specified otherwise, all the tables will be produced by cohort, and overall will not be 
displayed.
Unscheduled visits will not be summarized or included in any analysis but will be included in 
listings outputs.
12.1 Subject Disposition
The following information will be summarized for subject disposition by cohort in table based on 
SCR Analysis Set:
•
Number and percentage of subjects screened, 
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•
Number and percentage of screening failures and corresponding reasons for screening 
failure, 
•
Number and percentage of subjects included in each analysis set (EAS, FAS, and SAF).
Furthermore, following information will be provided by cohort in tables based on EAS.
•
Number and percentage of subjects who complete all the ingestions,
•
Number and percentage of subjects who complete study, 
•
Number and percentage of discontinuations from study and corresponding reasons for 
discontinuation,
The following reasons - as specified in the CRF - will be included in the disposition tables and in  
a listing (Listing: Enrollment and Study Completion for SCR Analysis Set):
Reasons for Screening Failure:
1. Failed Inclusion Criteria
2. Met Exclusion Criteria
3. Death
4. Adverse Event
5. Physician Decision
6. Pregnancy
7. Protocol Deviation
8. Terminated by Sponsor
9. Withdrawal by Subject
10. Other
Reasons for Study Discontinuation:
1. Death
2. Adverse Event
3. Lost to Follow-up
4. Non-compliance with Device/Patch
5. Physician decision
6. Pregnancy
7. Protocol Deviation
8. Terminated by Sponsor
9. Withdrawal by Subject
10. Withdrawal of Consent
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11. Other
12.2 Demographic and Baseline Characteristics
The following demographic and baseline data will be summarized in a table by cohort for the EAS. 
•
Age at informed consent (in years).
•
Sex at Birth: Female; Male. 
•
Gender Identification: Female; Male; Transgender Man; Transgender woman; Gender 
non-conforming; None of the above; Prefer not to answer; Other.
•
Race: American Indian or Alaska Native; Asian; Black or African American; Native 
Hawaiian or Other Pacific Islander; White; Other.
•
Ethnicity: Hispanic or Latino; Not Hispanic or Latino; Other; Unknown.
•
Childbearing Potential: Yes; No (the percentage of childbearing potential is based on the 
number of Females at birth).
•
Weight (kg)
•
Height (m)
•
BMI (kg/m²)
The demography and baseline data captured in the CRF will be included in a listing for EAS only.
12.2.1 Medical History
General medical history will be presented in the table by cohort for EAS, and the psychiatric 
medical history will be analyzed in the same manner. The number and percentage of subjects with 
each medical history term will be summarized by the Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class (SOC) and preferred term (PT). Medical history will be coded 
using MedDRA version 26.0 to assign a SOC and PT to each event. 
Separate listings for general medical history and psychiatric medical history will be included for 
EAS.
12.2.2 Prior and Concomitant Medications
Medications received prior or concomitantly with study drug (preferred base name), categorized 
by Anatomical Therapeutic Chemical (ATC) medication subgroup (ATC level 4) or subgroup 
(ATC level 3, 2 or 1, if level 4 is not available) according to WHODRUG (Version Global B3 
MARCH 2023), will be summarized separately in tables for EAS. The number and percentage of 
subjects using each medication will be displayed together with the number and percentage of 
subjects using at least one medication within each medication group and subgroup. 
Prior and concomitant medications will be included together but with “Concomitant Flag” in a 
listing for EAS.
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12.3 Device Application
12.3.1 Directly Observed Ingestion
The following directly observed ingestion (DOI) data for Cohort 1 will be summarized in Table 
together with positive detection (Section 12.5.1) and latency data (Section 12.5.2) for the FAS-
Cohort 1.
•
Number of ingestions (15 times; 14 times; 13 times; 12 times; 11 times; 10 times; 9 times; 
8 times; 7 times; 6 times; 5 times; 4 times; 3 times; 2 times; Once)
Furthermore, the above information will be provided in a listing based on FAS-Cohort 1 together 
with 
•
The reason if subject does not ingest the miniature IEM tablets
•
Date of ingestion
•
Time of each ingestion,
•
Volume of water (mL) ingested with placebo, 
•
Detection data
o
Patch serial number
o
Detected (True/False)
o
Patch impedance good (True/False)
o
Valid session (True/False)
o
Invalid session description
o
False positive (True/False)
•
Latency data
o
Patch serial number
o
Date and time of detected 
o
Date and time displayed 
o
Patch detection latency (seconds)
o
Ingestion data transfer latency (seconds)
o
Total detection latency (seconds)
•
Did the subject complete all the ingestions
•
Was the subject discontinued from completing all ingestions and the reason for 
discontinuation
12.3.2 Drug Exposure
Drug Exposure is not applicable for Cohort 1 because of placebo tablets. 
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For Cohort 2, subjects will ingest Abilify MyCite at the same dose as their currently prescribed 
aripiprazole. The following drug exposure data for Cohort 2 will be summarized in a table together 
with latency data for the FAS-Cohort 2.
•
The number and percentage of Abilify Dose ingested (2 mg; 5 mg; 10 mg; 15 mg; 20 mg 
and 30 mg).
Furthermore, above information will be provided in a listing based on FAS-Cohort 2, together 
with 
•
Date of Abilify MyCite ingestion 
•
Time of Abilify MyCite ingestion
•
Latency data
o
Patch serial number
o
Date and time of detected 
o
Date and time displayed 
o
Patch detection latency in seconds
o
Ingestion data transfer latency in seconds
o
Total detection latency in seconds
•
The reason if subject does not ingest the current prescribed dose of Abilify MyCite
•
Volume of water (mL) ingested with Abilify MyCite
12.3.3 Patch Application and Removal
As defined in Table 1, a minimum of three patch placement photos are required and recorded in 
the CRF: prior to initial dose, after completion of DOI(s), and when the subject returns for follow-
up (prior to patch removal). The following data will be provided in listings for FAS:
•
Photographs taken prior to initial dose (Yes or No; the reason if no; date and time of 
photography)
•
Patch Application completed (Yes or No; the reason if no; date and time of completion)
•
Photographs taken after DOIs (Yes or No; the reason if no; date and time of photography)
•
Was the subject instructed to keep the patch on as long as possible? (Yes or No)
•
Was subject instructed to return patch to the trial site during follow-up visit? (Yes or No)
•
Photographs taken prior to patch removal (Yes or No; the reason if no; date and time of 
photography)
•
Patch Removal completed (Yes or No; the reason if no; date of completion; Patch 
removal/fell off date and approximate time if it is not on the same date as the visit)
•
Patch returned (Yes or No; the reason if no)
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12.4 Protocol Deviations
The protocol deviations will be captured in CRF. Per protocol set is not applicable in this study, 
and no data review meeting is planned prior to database lock to finalize the evaluable subjects set. 
All protocol deviations will be listed only based on EAS.
12.5 Primary Analyses
The primary analyses including Positive Detection Accuracy and Detection Latency Measures are 
described in the following sections.
12.5.1 Positive Detection Accuracy
For FAS-Cohort 1, the number of positive detections, the positive detection accuracy (PDA) and 
95% Clopper-Pearson confidence interval (CI) will be summarized, for overall DOIs only. 
Positive detections will not be reported in CRF and will rather be downloaded from the trial mobile 
device(s). All positive detections data will be listed together with directly observed ingestion data 
(Section 12.3.1) based on FAS-Cohort 1.
12.5.2 Detection Latency Measures
As defined in Table 3, the directly observed ingestion time (TSE 1) is recorded in the CRF. Other 
signal detection times (TSE 2-4) will be downloaded from the trial mobile device(s) for analysis. 
The derivation of detection latency measures, including Patch Detection Latency, Ingestion Data 
Transfer Latency, and Total Detection Latency, are provided in Table 4.
The three detection latency measures for all DOIs will be summarized using descriptive statistics, 
for FAS-Cohort 1 and FAS-Cohort 2 separately. 
Furthermore, two Kaplan-Meier curves will be plotted for all of the latency times (all DOIs), for 
FAS-Cohort 1 and FAS-Cohort 2 separately. The three detection latency measures will be 
displayed as three curves on the plot. A table will be provided to show the summary of survival 
status, the median (50% survival time), and 25% and 75% percentiles of survival by Kaplan-Meier 
estimate. 
12.6 Safety Analyses
All safety analyses will be presented for the SAF.
12.6.1 Treatment-Emergent Adverse Events
All AEs reported in the CRF will be coded using MedDRA. 
An overall summary of TEAEs, including the number of events reported, and the number and 
percentage of subjects will be prepared by cohort in a table, as specified below:
•
Subjects reporting at least 1 TEAE
•
Subjects reporting at least 1 serious TEAE
•
Subjects reporting at least 1 device/patch related TEAE
•
Subjects reporting at least 1 device/patch related TEAE (by skin irritation score from 0-7)
Synopsis Clinical Study Report  031-201-00521
4.1.5 Documentation of Statistical Methods
Until the information herein is released by Otsuka to the public domain, the contents of this document are Otsuka
confidential information and should not be duplicated or re-distributed without prior written consent of Otsuka.
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Statistical Analysis Plan (SAP) 
Version Date: 22-JUN-2023 
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Protocol No: 031-201-00521
Page 18 of 20
Strictly Confidential.  © 2023, PRA Health Sciences.  All rights reserved.
•
Subjects reporting at least 1 clinically significant TEAE (defined by skin irritation score ≥ 
2)
•
Subjects reporting at least 1 Abilify MyCite treatment related TEAE (Cohort 2 only)
•
Subject reported receiving at least 1 TEAE with concomitant or additional therapy
•
Subjects with any TEAE leading to death
•
Subjects discontinuing the study due to a TEAE
•
Subjects discontinuing the study due to a device/patch related TEAE
•
Subjects discontinuing the study due to an Abilify MyCite treatment related TEAE
Furthermore, a breakdown of the number and percentage of subjects reporting TEAE, 
categorized by system organ class (SOC) and preferred term (PT) coded according to the 
MedDRA dictionary (Version 26.0), will be presented. Note that counting will be by subject not 
event and subjects are only counted once within each SOC or PT. Therefore, when counting the 
number of subjects with each event, subjects with multiple events within a particular SOC or PT 
will be counted under the category of their most severe event within that SOC or PT. The list of 
TEAE tables is the following:
•
TEAEs by SOC and PT
•
Clinically significant TEAEs (defined as device/patch related TEAE and skin irritation 
score ≥ 2) by SOC and PT
•
Any TEAE by maximum severity (mild, moderate, severe) by SOC and PT
•
Any TEAE related to study device/patch by SOC and PT
•
Any TEAE related to Abilify MyCite treatment by SOC and PT (Cohort 2 only)
•
Serious TEAEs by SOC and PT
•
TEAE leading to death by SOC and PT
•
TEAEs leading to study discontinuation by SOC and PT
All AEs recorded on the CRF will be listed with MedDRA SOC and PT. The TEAEs will be marked 
with a flag within the listing. A footnote will state if no AE occurred after screening and before the 
subject wore any patches or took any tablet.
Independent listings will be provided with MedDRA SOC and PT for:
•
Device/Patch related TEAEs (with skin irritation score evaluation), 
•
Abilify MyCite treatment related TEAEs (Cohort 2 only), 
•
TEAEs leading to study discontinuation
12.6.2 Deaths and Serious TEAEs
As already described in previous section, a summary table for TEAE leading to death and for 
serious TEAEs will be provided by SOC and PT.
Synopsis Clinical Study Report  031-201-00521
4.1.5 Documentation of Statistical Methods
Until the information herein is released by Otsuka to the public domain, the contents of this document are Otsuka
confidential information and should not be duplicated or re-distributed without prior written consent of Otsuka.
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Statistical Analysis Plan (SAP) 
Version Date: 22-JUN-2023 
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Protocol No: 031-201-00521
Page 19 of 20
Strictly Confidential.  © 2023, PRA Health Sciences.  All rights reserved.
A listing for all serious TEAEs and for all TEAE leading to death will be prepared. 
12.6.3 Laboratory Data
Laboratory data is not applicable in this study.
12.6.4 Vital Signs
Vital sign measurements will be collected at Screening (Visit 1) only, the following vital signs will 
be summarized in a table:
•
Systolic Blood Pressure (mmHg)
•
Diastolic Blood Pressure (mmHg)
•
Heart Rate (bpm)
•
Body Temperature (Fahrenheit)
Vital signs data including abnormal and clinically significant results will be provided in a listing.
13.0 Glossary of Abbreviations
Glossary of Abbreviations:
AE
Adverse event
ATC
Anatomic Therapeutic Chemical
CI
Confidence Interval
COVID-19
Coronavirus disease 2019
CRF
Case Report Form
DOI
Directly Observed Ingestion
EAS
Enrolled Analysis Set
FAS
Full Analysis Set
ICF
Informed Consent Form
IEM
Ingestible Event Marker
MedDRA
Medical Dictionary for Regulatory Activities
MIT
Miniature ingestible event marker tablet
PDA
Positive Detection Accuracy
SAP
Statistical Analysis Plan
SAE
Serious Adverse Event
SAF
Safety Analysis Set
SCR
Screened Analysis Set
SMI
Serious Mental Illness
Synopsis Clinical Study Report  031-201-00521
4.1.5 Documentation of Statistical Methods
Until the information herein is released by Otsuka to the public domain, the contents of this document are Otsuka
confidential information and should not be duplicated or re-distributed without prior written consent of Otsuka.
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Statistical Analysis Plan (SAP) 
Version Date: 22-JUN-2023 
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Protocol No: 031-201-00521
Page 20 of 20
Strictly Confidential.  © 2023, PRA Health Sciences.  All rights reserved.
SOC
System Organ Class
PDA
Positive Detection Accuracy
PT
Preferred Term
TEAE
Treatment-Emergent Adverse Event
TSE
Time-Stamped Event
Synopsis Clinical Study Report  031-201-00521
4.1.5 Documentation of Statistical Methods
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confidential information and should not be duplicated or re-distributed without prior written consent of Otsuka.
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SIGNATURE PAGE
Document Name: OTABEV04-0D1P6W_Statistical Analysis Plan (SAP) text v1.0
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Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:min) -
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Clinical Approval
28-Jun-2023
16:30:12
Biostatistics Approval
28-Jun-2023
13:25:56
Synopsis Clinical Study Report  031-201-00521
4.1.5 Documentation of Statistical Methods
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confidential information and should not be duplicated or re-distributed without prior written consent of Otsuka.
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