A Trial to Explore Acceptance and Performance of Using a Digital Medicine System With Healthcare Professionals and Adults With Schizophrenia, Schizoaffective Disorder, or First Episode Psychosis on an Oral Atypical Antipsychotic

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03568500
• Collaborator: (none)
• Enrollment: 44
• Locations: 5
• Arms: 4
• Actual Duration (Months): 15.5
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Digital medicine systems (DMS) have been designed to assist individuals with the management of their daily health, wellness, and medication use. The DMS is being developed as a healthcare management tool to precisely measure medication adherence and to potentially enhance adherence.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder; First Episode Psychosis	Device: Digital Medicine System; Drug: Aripiprazole; Drug: Olanzapine; Drug: Quetiapine; Drug: Risperidone	Phase 4

Detailed Description

The advancements in the treatment of mental health patients with DMS will enable healthcare professionals to assess suboptimal adherence and make more informed treatment decisions. In addition to these improvements, it will also provide a platform for engagement between participants, healthcare professionals, and caregivers/support persons.

Participants who entered the trial were treated with one of the oral atypical antipsychotics defined in the trial (aripiprazole, olanzapine, quetiapine, or risperidone [though no participant took risperidone in this trial]). The treatment medication decision was determined by the healthcare professionals.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Health Services Research
• Official Title: A Multicentre, 8-week, Single-arm, Open-label, Pragmatic Trial to Explore Acceptance and Performance of Using a Digital Medicine System With Healthcare Professionals and Adult Subjects With Schizophrenia, Schizoaffective Disorder, or First Episode Psychosis on an Oral Atypical Antipsychotic (Aripiprazole, Olanzapine, Quetiapine, or Risperidone)
• Actual Study Start Date: May 21, 2018
• Actual Primary Completion Date: May 21, 2019
• Actual Study Completion Date: Sep 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole Participants received 1 oral tablet of CoEncapsulated (CoE) aripiprazole, wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks.	Device: Digital Medicine System; DMS components: a CoE product consisting of an approved antipsychotic medicinal product co-encapsulated with Conformité Européenne (CE)-marked miniature ingestible event marker in tablet; a CE-marked compatible medical device (a Proteus Patch [Disposable Wearable Sensor Version 5]); proprietary medical software (a local and remote computing application).; Drug: Aripiprazole; Dosage determined by the healthcare professionals.
Experimental: Olanzapine Participants received 1 oral tablet of CoE olanzapine, wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks.	Device: Digital Medicine System; DMS components: a CoE product consisting of an approved antipsychotic medicinal product co-encapsulated with Conformité Européenne (CE)-marked miniature ingestible event marker in tablet; a CE-marked compatible medical device (a Proteus Patch [Disposable Wearable Sensor Version 5]); proprietary medical software (a local and remote computing application).; Drug: Olanzapine; Dosage determined by the healthcare professionals.
Experimental: Quetiapine Participants received 1 oral tablet of CoE quetiapine, wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks.	Device: Digital Medicine System; DMS components: a CoE product consisting of an approved antipsychotic medicinal product co-encapsulated with Conformité Européenne (CE)-marked miniature ingestible event marker in tablet; a CE-marked compatible medical device (a Proteus Patch [Disposable Wearable Sensor Version 5]); proprietary medical software (a local and remote computing application).; Drug: Quetiapine; Dosage determined by the healthcare professionals.
Experimental: Risperidone Participants were to receive 1 oral tablet of CoE risperidone, wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks. No participant took risperidone in this trial.	Device: Digital Medicine System; DMS components: a CoE product consisting of an approved antipsychotic medicinal product co-encapsulated with Conformité Européenne (CE)-marked miniature ingestible event marker in tablet; a CE-marked compatible medical device (a Proteus Patch [Disposable Wearable Sensor Version 5]); proprietary medical software (a local and remote computing application).; Drug: Risperidone; Dosage determined by the healthcare professionals.

Outcome Measures

Primary Outcome Measures

1. Percentage Of Days With Good Patch Coverage [Up to 8 weeks]

   The DMS includes a drug-device combination of a CoE product, a wearable sensor patch, and application software (smartphone) to record activity and rest and mark events through the act of ingestion. The CoE product consists of an approved antipsychotic medication enclosed with an Ingestible Sensor Pill (miniature ingestible event marker in tablet [MIT]). The sensor patch detects and records each MIT ingestion, as well as other physiologic and behavioral data. Good patch coverage for a specific day was defined as having either at least 80% patch data available (80% of the day the patch was worn and data was collected as noted via the accelerometer channel) or the MIT was detected within the 24-hour period, for each day while the participant was in the trial. The percentage of days was calculated as the number of days with good patch coverage divided by the total number of trial days for each participant. Descriptive statistics were performed for this outcome measure.

Secondary Outcome Measures

1. Participant Adherence [Up to 8 weeks]

   The DMS includes a drug-device combination of a CoE product, a wearable sensor patch, and application software (smartphone) to record activity and rest and mark events through the act of ingestion. The CoE product consists of an approved antipsychotic medication enclosed with an Ingestible Sensor Pill (MIT). The sensor patch detects and records each MIT ingestion, as well as other physiologic and behavioral data. Participant adherence was measured as the detected MITs over the expected MITs ingested during the trial days with good patch coverage. The more the participant successfully engaged in a number of processes across the 8-week trial, the greater the measured adherence. Descriptive statistics were performed for this outcome measure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant was prescribed aripiprazole, olanzapine, quetiapine, or risperidone.

• Participant possessed a smartphone, or a smartphone provided by the Sponsor, and was willing to download and interact with the DMS app.

• Skin on the anterior chest just above the lower edge of the rib cage was free of any dermatological problems (for example, open wounds, warts, rashes, atopic dermatitis).

Exclusion Criteria:

• Participant with a known allergy to adhesive tape or any pertinent components of the patch or CoE product.

• Prisoners could not be enrolled into this trial.

• Participant who was hospitalized due to mental or physical illness (inpatient) at the time of screening/baseline.

• Any participant who, through religious or lifestyle choices, would not take gelatin capsules.

• Female of childbearing potential who was breast-feeding and/or who had a positive pregnancy test result prior to receiving trial enrollment, or who planned to become pregnancy during the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Chertsey		United Kingdom
2	Clinical Trial Site	London		United Kingdom
3	Clinical Trial Site	Newcastle Upon Tyne		United Kingdom
4	Clinical Trial Site	Oxford		United Kingdom
5	Clinical Trial Site	Southampton		United Kingdom

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol: Version 1.0 - Dec 1, 2017
• Study Protocol: Version 2.0 - Jan 4, 2019
• Statistical Analysis Plan - Jun 30, 2019

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT03568500
• Other Study ID Numbers: 031-201-00186
• First Posted: Jun 26, 2018
• Last Update Posted: Jul 16, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Digital Medicine System
• Additional relevant MeSH terms: Schizophrenia; Psychotic Disorders; Mental Disorders; Olanzapine; Risperidone; Aripiprazole; Quetiapine Fumarate

Study Results

Participant Flow

Recruitment Details	The trial enrolled participants with a confirmed clinical diagnosis of schizophrenia, schizoaffective disorder, or first episode psychosis.
Pre-assignment Detail	Participants in this trial received at least 1 CoEncapsulated miniature ingestible event marker in a tablet and a medicinal product originator tablet of either aripiprazole, olanzapine, or quetiapine (participants were allowed to take risperidone, though no participant took risperidone in this trial) as prescribed by their healthcare professional.

Arm/Group Title	Aripiprazole	Olanzapine	Quetiapine
Arm/Group Description	Participants were treated with at least 1 CoEncapsulated (CoE) oral aripiprazole tablet, wearing the digital medicine system (DMS) patch, and using the associated smartphone app for a total of 8 weeks.	Participants were treated with at least 1 CoE oral olanzapine tablet, wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks.	Participants were treated with at least 1 CoE oral quetiapine tablet, wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks.
Period Title: Overall Study
STARTED	18	20	6
Received At Least 1 Dose of Study Drug	18	19	6
COMPLETED	8	14	2
NOT COMPLETED	10	6	4

Baseline Characteristics

Arm/Group Title	Aripiprazole	Olanzapine	Quetiapine	Total
Arm/Group Description	Participants were treated with at least 1 CoEncapsulated (CoE) oral aripiprazole tablet, wearing the digital medicine system (DMS) patch, and using the associated smartphone app for a total of 8 weeks.	Participants were treated with at least 1 CoE oral olanzapine tablet, wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks.	Participants were treated with at least 1 CoE oral quetiapine tablet, wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks.	Total of all reporting groups
Overall Participants	18	20	6	44
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	31.6 (9.6)	38.0 (11.4)	30.8 (8.8)	34.4 (10.7)
Sex: Female, Male (Count of Participants)
Female	8 44.4%	4 20%	3 50%	15 34.1%
Male	10 55.6%	16 80%	3 50%	29 65.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	17 94.4%	18 90%	5 83.3%	40 90.9%
Unknown or Not Reported	1 5.6%	2 10%	1 16.7%	4 9.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	4 22.2%	4 20%	0 0%	8 18.2%
White	14 77.8%	15 75%	6 100%	35 79.5%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 5%	0 0%	1 2.3%
Disease Diagnosis (Count of Participants)
Schizophrenia	5 27.8%	13 65%	0 0%	18 40.9%
Schizoaffective Disorder	4 22.2%	4 20%	2 33.3%	10 22.7%
First Episode Psychosis	9 50%	3 15%	4 66.7%	16 36.4%

Outcome Measures

1. Primary Outcome

Title	Percentage Of Days With Good Patch Coverage
Description	The DMS includes a drug-device combination of a CoE product, a wearable sensor patch, and application software (smartphone) to record activity and rest and mark events through the act of ingestion. The CoE product consists of an approved antipsychotic medication enclosed with an Ingestible Sensor Pill (miniature ingestible event marker in tablet [MIT]). The sensor patch detects and records each MIT ingestion, as well as other physiologic and behavioral data. Good patch coverage for a specific day was defined as having either at least 80% patch data available (80% of the day the patch was worn and data was collected as noted via the accelerometer channel) or the MIT was detected within the 24-hour period, for each day while the participant was in the trial. The percentage of days was calculated as the number of days with good patch coverage divided by the total number of trial days for each participant. Descriptive statistics were performed for this outcome measure.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All participants who entered the trial and used the DMS.

Arm/Group Title	Schizophrenia	Schizoaffective Disorder	First Episode Psychosis	Total
Arm/Group Description	Participants had a confirmed clinical diagnosis of schizophrenia (defined by International Classification of Disease-10 codes F20 and F25). There was no limit on the duration of illness. Participants were treated with at least 1 CoE oral atypical antipsychotic tablet (aripiprazole, olanzapine, or quetiapine), wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks. The treatment medication decision was determined by the healthcare professional.	Participants had a confirmed clinical diagnosis of schizoaffective disorder (defined by International Classification of Disease-10 codes F20 and F25). There was no limit on the duration of illness. Participants were treated with at least 1 CoE oral atypical antipsychotic tablet (aripiprazole, olanzapine, or quetiapine), wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks. The treatment medication decision was determined by the healthcare professional.	Participants had a confirmed clinical diagnosis of first episode psychosis using case note review. The duration of illness was defined as less than 3 years since presentation to the mental health team or first antipsychotic prescription. Participants were treated with at least 1 CoE oral atypical antipsychotic tablet (aripiprazole, olanzapine, or quetiapine), wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks. The treatment medication decision was determined by the healthcare professional.	Participants were treated with at least 1 CoE oral atypical antipsychotic tablet (aripiprazole, olanzapine, or quetiapine), wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks. The treatment medication decision was determined by the healthcare professional.
Measure Participants	18	9	16	43
Mean (Standard Deviation) [percentage of days]	64.34 (20.24)	62.99 (37.68)	62.51 (27.53)	63.37 (26.60)

2. Secondary Outcome

Title	Participant Adherence
Description	The DMS includes a drug-device combination of a CoE product, a wearable sensor patch, and application software (smartphone) to record activity and rest and mark events through the act of ingestion. The CoE product consists of an approved antipsychotic medication enclosed with an Ingestible Sensor Pill (MIT). The sensor patch detects and records each MIT ingestion, as well as other physiologic and behavioral data. Participant adherence was measured as the detected MITs over the expected MITs ingested during the trial days with good patch coverage. The more the participant successfully engaged in a number of processes across the 8-week trial, the greater the measured adherence. Descriptive statistics were performed for this outcome measure.
Time Frame	Up to 8 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All participants who entered the trial, used the DMS, and had data available at the specified timepoint.

Arm/Group Title	Schizophrenia	Schizoaffective Disorder	First Episode Psychosis	Total
Arm/Group Description	Participants had a confirmed clinical diagnosis of schizophrenia (defined by International Classification of Disease-10 codes F20 and F25). There was no limit on the duration of illness. Participants were treated with at least 1 CoE oral atypical antipsychotic tablet (aripiprazole, olanzapine, or quetiapine), wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks. The treatment medication decision was determined by the HCP.	Participants had a confirmed clinical diagnosis of schizoaffective disorder (defined by International Classification of Disease-10 codes F20 and F25). There was no limit on the duration of illness. Participants were treated with at least 1 CoE oral atypical antipsychotic tablet (aripiprazole, olanzapine, or quetiapine), wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks. The treatment medication decision was determined by the HCP.	Participants had a confirmed clinical diagnosis of first episode psychosis using case note review. The duration of illness was defined as less than 3 years since presentation to the mental health team or first antipsychotic prescription. Participants were treated with at least 1 CoE oral atypical antipsychotic tablet (aripiprazole, olanzapine, or quetiapine), wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks. The treatment medication decision was determined by the HCP.	Participants were treated with at least 1 CoE oral atypical antipsychotic tablet (aripiprazole, olanzapine, or quetiapine), wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks. The treatment medication decision was determined by the healthcare professional.
Measure Participants	18	8	16	42
Mean (Standard Deviation) [percentage of MITs]	88.94 (8.06)	72.29 (25.65)	91.04 (7.37)	86.57 (14.47)

Adverse Events

Time Frame	Baseline to Week 24 (+ 7 days)
Arm/Group Title	Aripiprazole		Olanzapine		Quetiapine		Total
Arm/Group Description	Participants were treated with at least 1 CoEncapsulated (CoE) oral aripiprazole tablet, wearing the digital medicine system (DMS) patch, and using the associated smartphone app for a total of 8 weeks.		Participants were treated with at least 1 CoE oral olanzapine tablet, wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks.		Participants were treated with at least 1 CoE oral quetiapine tablet, wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks.		Participants were treated with at least 1 CoE oral atypical antipsychotic tablet (aripiprazole, olanzapine, or quetiapine), wearing the DMS patch, and using the associated smartphone app for a total of 8 weeks. The treatment medication decision was determined by the healthcare professional.
All Cause Mortality
	Aripiprazole		Olanzapine		Quetiapine		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/19 (0%)		0/6 (0%)		0/43 (0%)
Serious Adverse Events
	Aripiprazole		Olanzapine		Quetiapine		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/19 (0%)		0/6 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Aripiprazole		Olanzapine		Quetiapine		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/18 (22.2%)		2/19 (10.5%)		3/6 (50%)		9/43 (20.9%)
General disorders
Medical device site irritation	4/18 (22.2%)	5	2/19 (10.5%)	2	3/6 (50%)	4	9/43 (20.9%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.