Trial Outcomes & Findings for Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Acute Schizophrenia (NCT NCT02054702)

NCT ID: NCT02054702

Last Updated: 2015-12-30

Results Overview

The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 97 participants
• Primary outcome timeframe: Baseline to Week 6
• Results posted on: 2015-12-30

Participant Flow

The trial was conducted in 97 participants at 19 trial sites in United States.

The trial consisted of a 2- to 14-day screening phase, a 6-week treatment phase, and a 30-day follow-up phase.

Participant milestones

Measure	Brexpiprazole Participants were administered brexpiprazole tablets orally, once daily (QD) starting dose at 1 milligram per day (mg/day) for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Overall Study STARTED	64	33
Overall Study COMPLETED	40	21
Overall Study NOT COMPLETED	24	12

Reasons for withdrawal

Measure	Brexpiprazole Participants were administered brexpiprazole tablets orally, once daily (QD) starting dose at 1 milligram per day (mg/day) for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Overall Study Lost to Follow-up	3	5
Overall Study Adverse Event	3	1
Overall Study Met Withdrawal Criteria	4	1
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	14	4

Baseline Characteristics

Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Acute Schizophrenia

Baseline characteristics by cohort

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Arpiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.	Total n=97 Participants Total of all reporting groups
Age, Continuous	42.2 Years STANDARD_DEVIATION 10.1 • n=93 Participants	42.1 Years STANDARD_DEVIATION 10.4 • n=4 Participants	42.2 Years STANDARD_DEVIATION 10.2 • n=27 Participants
Sex: Female, Male Female	18 Participants n=93 Participants	10 Participants n=4 Participants	28 Participants n=27 Participants
Sex: Female, Male Male	46 Participants n=93 Participants	23 Participants n=4 Participants	69 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. The efficacy analyses were performed by fitting a mixed model repeated measures (MMRM) analysis with an unstructured variance covariance structure.

The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score	-22.9 Units on a scale Standard Error 1.7	-19.4 Units on a scale Standard Error 2.4

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. The efficacy analyses were performed by fitting a MMRM analysis with an unstructured variance covariance structure.

The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement.

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Change From Baseline in Cognitive Test Battery Composite Score	0.045 z-score Standard Error 0.056	-0.024 z-score Standard Error 0.081

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. The efficacy analyses were performed by fitting a MMRM analysis with an unstructured variance covariance structure.

The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement. The cognitive test early phase battery was analyzed; tasks included Groton Maze Learning Task, Detection Task, Identification Task, and One Card Learning Task.

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Change From Baseline in Cognitive Test Battery of Early Phase Battery Score	-0.010 z-score Standard Error 0.063	0.113 z-score Standard Error 0.091

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment.

The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement.

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Change From Baseline in Cognitive Test Battery Scores of Groton Maze Learning (GML)	0.7 z-score Standard Error 3.7	-4.6 z-score Standard Error 5.1

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. The efficacy analyses were performed by fitting a MMRM analysis with an unstructured variance covariance structure.

The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement.

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Change From Baseline in Cognitive Test Battery Scores of Detection Task	0.024 z-score Standard Error 0.018	-0.029 z-score Standard Error 0.026

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. The efficacy analyses were performed by fitting a MMRM analysis with an unstructured variance covariance structure.

The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement.

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Change From Baseline in Cognitive Test Battery Scores of Identification Task	-0.002 z-score Standard Error 0.011	-0.011 z-score Standard Error 0.016

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. The efficacy analyses were performed by fitting a MMRM analysis with an unstructured variance covariance structure.

The cognitive test battery contains 8-tasks, including the Detection Task (DET, speed of processing), Identification Task (IDN, attention/vigilance), One Card Learning Task (OCL, visual learning), One-back Memory Task (ONB, working memory), Two Back Task (TWOB, working memory), the Groton Maze Learning Task (GML, problem solving/error monitoring), Social Emotional Cognition Task (SECT, social cognition), International shopping List Task (ISL, verbal learning and memory). The results of each domain on the cognitive test battery were calculated into Z-scores, where the healthy control mean was set to zero and the standard deviation to 1. A composite score was generated, with higher values representing better cognitive performance. The composite score is then the mean of z-scores for appropriate tasks where z-score = - 1 × z-score for DET, GML, IDN and ONB to correct for the direction of improvement.

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Change From Baseline in Cognitive Test Battery Scores of One Card Learning Task	0.003 z-score Standard Error 0.018	0.000 z-score Standard Error 0.027

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. The efficacy analyses were performed by fitting a MMRM analysis with an unstructured variance covariance structure.

The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score	-1.6 Units on a scale Standard Error 0.1	-1.3 Units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. Analysis was performed on the LOCF dataset.

The efficacy of trial medication was rated for each participant using the CGI-I. The study physician would rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at Baseline prior to the first dose of double-blind study medication. Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Mean Change in Clinical Global Impression-Improvement (CGI-I) Score at Week 6	2.5 Units on a scale Standard Deviation 0.9	2.7 Units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. Analysis was performed on the LOCF dataset.

The response rate was defined as reduction of ≥30% from Baseline in PANSS Total Score or CGI-I score of of 1 (very much improved) or 2 (much improved).

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Response Rate by Study Week	60.9 percentage of participants	48.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. Analysis was performed on the LOCF dataset.

The SLOF questionnaire used in this trial consisted of 30 items grouped into 4 areas: interpersonal relationships, social acceptability, activities, and work skill. The SLOF correlates with a subject's quality of life. Each of the questions in the domains is rated on a 5-point Likert scale ranging from 1 "not well at all" to 5 "very well". The possible total score range for SLOF is from 30 to 150, higher score indicating better overall functioning of the participant.

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Change From Baseline to Week 6 in Specific Levels of Functioning Scale (SLOF) Total Score	7.5 Units on a scale Interval 4.0 to 10.9	6.0 Units on a scale Interval 1.2 to 10.8

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: All randomized participants who took at least one dose of study medication and who had a valid Baseline assessment and at least 1 valid Post-Baseline efficacy assessment. Analysis was performed on the LOCF dataset.

The BIS-11, a subject-rated scale designed to assess impulsive personality traits, was administered at the baseline and Week 6 visits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provided information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, nonplanning impulsiveness, and attentional impulsiveness). The total score ranged from 30 to 120, higher scores indicate better personality trait.

Outcome measures

Measure	Brexpiprazole n=64 Participants Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 Participants Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11 Item) Total Score	-2.6 Units on a scale Interval -5.0 to -0.1	-0.1 Units on a scale Interval -3.5 to 3.3

Adverse Events

Brexpiprazole

Serious events: 3 serious events

Other events: 36 other events

Deaths: 0 deaths

Aripiprazole

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Brexpiprazole n=64 participants at risk Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 participants at risk Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Infections and infestations Acute hepatitis B	1.6% 1/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	0.00% 0/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Nervous system disorders Convulsion	1.6% 1/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	0.00% 0/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Nervous system disorders Presynscope	0.00% 0/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	3.0% 1/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Psychiatric disorders Schizophrenia	1.6% 1/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	0.00% 0/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.

Other adverse events

Measure	Brexpiprazole n=64 participants at risk Participants were administered brexpiprazole tablets orally QD, starting dose at 1 mg/day for 4 days followed by 2 mg/day for 3 days and 3 mg/day at the week 1 visit and 1, 2, 3, or 4 mg/day from week 2 to week 6.	Aripiprazole n=33 participants at risk Participants were administered aripiprazole tablets orally QD, starting dose at 10 mg/day for 1 week, followed by 15 mg/day at the Week 1 visit and 10, 15, or 20 mg/day from week 2 to week 6.
Gastrointestinal disorders Dry mouth	7.8% 5/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	6.1% 2/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Gastrointestinal disorders Dyspepsia	7.8% 5/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	9.1% 3/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Gastrointestinal disorders Nausea	6.2% 4/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	3.0% 1/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Investigations Weight increased	9.4% 6/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	9.1% 3/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Musculoskeletal and connective tissue disorders Pain in extremity	6.2% 4/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	3.0% 1/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Nervous system disorders Akathisia	9.4% 6/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	21.2% 7/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Nervous system disorders Headache	7.8% 5/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	12.1% 4/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Gastrointestinal disorders Constipation	4.7% 3/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	9.1% 3/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Gastrointestinal disorders Diarrhoea	4.7% 3/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	6.1% 2/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Musculoskeletal and connective tissue disorders Back pain	3.1% 2/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	6.1% 2/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Musculoskeletal and connective tissue disorders Muscle spasm	0.00% 0/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	6.1% 2/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Nervous system disorders Sedation	0.00% 0/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	6.1% 2/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.
Gastrointestinal disorders Toothache	0.00% 0/64 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.	6.1% 2/33 • Adverse events were reported from the signing of informed consent throughout the 6-week treatment period until the follow-up visit 30 days (+2) after the last dose of study medication. Participants with adverse events were counted only once towards the total.

Additional Information

Global Medical Affairs

Otsuka Pharmaceutical Development and Commercialization, Inc.

Phone: 800 562-3974

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place