Trial Outcomes & Findings for Multicenter, Open-label, Safety and Tolerability Study (NCT NCT01649557)

NCT ID: NCT01649557

Last Updated: 2015-10-29

Results Overview

AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the investigator. A serious adverse event (SAE) was any untoward medical occurrence that resulted in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. A treatment-emergent AE (TEAE) was defined as an AE that started after start of study medication or an AE that continued from baseline and that worsened, was serious, was study medication related, or resulted in death, discontinuation, interruption, or reduction of study medication.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 244 participants
• Primary outcome timeframe: From Baseline up to 6 weeks
• Results posted on: 2015-10-29

Participant Flow

The protocol was initially approved as a 6-week trial and later extended to a 52-week trial (Amendment 2). The trial enrolled 244 participants at 73 sites in 12 countries. Of the 244 participants, 28 were included in the 52-week enrollment population.

Trial consisted of a screening visit, treatment phase and safety follow-up at 30 (± 2) days after the last dose of medication. Eligible participants for the trial were those who completed protocol NCT00905307 and who in the investigators judgment would benefit from the treatment.

Participant milestones

Measure	Prior Brexpiprazole The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Overall Study STARTED	179	41	24
Overall Study 6-week Enrollers	159	35	22
Overall Study 52-week Enrollers	20	6	2
Overall Study COMPLETED	135	27	15
Overall Study NOT COMPLETED	44	14	9

Reasons for withdrawal

Measure	Prior Brexpiprazole The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Overall Study Lost to Follow-up	5	0	3
Overall Study Adverse Event	7	5	1
Overall Study Met withdrawal criteria	4	0	0
Overall Study Physician Decision	8	2	1
Overall Study Withdrawal by Subject	15	5	4
Overall Study Protocol deviation	0	2	0
Overall Study Lack of Efficacy	5	0	0

Baseline Characteristics

Multicenter, Open-label, Safety and Tolerability Study

Baseline characteristics by cohort

Measure	Prior Brexiprazole n=179 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Apripiprazole n=24 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Total n=244 Participants Total of all reporting groups
Age, Continuous	39.1 Years STANDARD_DEVIATION 10.1 • n=5 Participants	41.4 Years STANDARD_DEVIATION 11.2 • n=7 Participants	41.2 Years STANDARD_DEVIATION 12 • n=5 Participants	39.7 Years STANDARD_DEVIATION 10.5 • n=4 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	17 Participants n=7 Participants	5 Participants n=5 Participants	91 Participants n=4 Participants
Sex: Female, Male Male	110 Participants n=5 Participants	24 Participants n=7 Participants	19 Participants n=5 Participants	153 Participants n=4 Participants

PRIMARY outcome

Timeframe: From Baseline up to 6 weeks

Population: The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole and were enrolled in the 6-week study.

AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the investigator. A serious adverse event (SAE) was any untoward medical occurrence that resulted in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. A treatment-emergent AE (TEAE) was defined as an AE that started after start of study medication or an AE that continued from baseline and that worsened, was serious, was study medication related, or resulted in death, discontinuation, interruption, or reduction of study medication.

Outcome measures

Measure	Prior Brexpiprazole n=178 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=23 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Number of Participants With Adverse Events (AEs) During First 6 Weeks. Participants with AEs	79 Participants	19 Participants	7 Participants
Number of Participants With Adverse Events (AEs) During First 6 Weeks. Participants with TEAEs	78 Participants	19 Participants	7 Participants
Number of Participants With Adverse Events (AEs) During First 6 Weeks. Participants with serious TEAEs	4 Participants	6 Participants	1 Participants
Number of Participants With Adverse Events (AEs) During First 6 Weeks. Participants with severe TEAEs	2 Participants	3 Participants	2 Participants

PRIMARY outcome

Timeframe: From Baseline up to 52 weeks

Population: Those participants who received at least one dose of open-label brexpiprazole and who were enrolled in the 52-week study.

AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the investigator. A SAE was any untoward medical occurrence that resulted in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. A TEAE was defined as an AE that started after start of study medication or an AE that continued from baseline and that worsened, was serious, was study medication related, or resulted in death, discontinuation, interruption, or reduction of study medication.

Outcome measures

Measure	Prior Brexpiprazole n=20 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=6 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=2 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Number of Participants With AEs in 52-Week Enrollers. Participants with AEs	15 Participants	4 Participants	2 Participants
Number of Participants With AEs in 52-Week Enrollers. Participants with TEAEs	15 Participants	4 Participants	2 Participants
Number of Participants With AEs in 52-Week Enrollers. Participants with serious TEAEs	0 Participants	0 Participants	0 Participants
Number of Participants With AEs in 52-Week Enrollers. Participants with severe TEAEs	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit

Population: The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. The PANSS total score ranges from 30-210, with higher scores indicating more severe symptoms.

Outcome measures

Measure	Prior Brexpiprazole n=178 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=23 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Last visit (N= 176, 41, 23)	-5.99 Units on a scale Standard Deviation 11.25	-2.32 Units on a scale Standard Deviation 18.97	-5.96 Units on a scale Standard Deviation 8.27
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Day 4 (N= 169, 36, 22)	0.11 Units on a scale Standard Deviation 5.86	-1.25 Units on a scale Standard Deviation 3.97	-1.50 Units on a scale Standard Deviation 4.97
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 1 (N= 167, 40, 23)	-2.03 Units on a scale Standard Deviation 5.49	-1.53 Units on a scale Standard Deviation 7.95	-1.91 Units on a scale Standard Deviation 6.22
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 2 (N= 165, 40, 21)	-2.95 Units on a scale Standard Deviation 8.80	-3.43 Units on a scale Standard Deviation 10.68	-1.86 Units on a scale Standard Deviation 6.04
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 4 (N=148, 34, 18)	-4.65 Units on a scale Standard Deviation 8.59	-4.71 Units on a scale Standard Deviation 12.85	-5.39 Units on a scale Standard Deviation 6.30
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 6 (N= 138, 31, 15)	-7.51 Units on a scale Standard Deviation 8.82	-7.87 Units on a scale Standard Deviation 10.26	-7.47 Units on a scale Standard Deviation 7.22
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 8 (N=20, 6, 2)	-8.80 Units on a scale Standard Deviation 8.69	-5.17 Units on a scale Standard Deviation 7.55	-10.00 Units on a scale Standard Deviation 1.41
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 14 (N=20, 6, 2)	-9.85 Units on a scale Standard Deviation 8.09	6.83 Units on a scale Standard Deviation 28.29	-3.50 Units on a scale Standard Deviation 12.02
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 20 (N= 20, 5, 2)	-10.20 Units on a scale Standard Deviation 9.12	-4.60 Units on a scale Standard Deviation 10.71	-6.50 Units on a scale Standard Deviation 10.61
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 26 (N= 19, 5, 2)	-12.89 Units on a scale Standard Deviation 9.34	-5.80 Units on a scale Standard Deviation 11.56	-10.50 Units on a scale Standard Deviation 7.78
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 32 (N= 18, 5, 2)	-14.67 Units on a scale Standard Deviation 10.94	-3.00 Units on a scale Standard Deviation 16.90	-16.00 Units on a scale Standard Deviation 0.00
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 38 (N= 17, 3, 2)	-13.24 Units on a scale Standard Deviation 10.97	-4.67 Units on a scale Standard Deviation 10.21	-13.00 Units on a scale Standard Deviation 0.00
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 44 (N= 17, 2, 2)	-16.00 Units on a scale Standard Deviation 10.28	-4.50 Units on a scale Standard Deviation 12.02	-11.50 Units on a scale Standard Deviation 2.12
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) by Study Week and at the Last Visit. Week 52 (N= 16, 2, 2)	-15.00 Units on a scale Standard Deviation 10.06	-5.50 Units on a scale Standard Deviation 13.44	-11.00 Units on a scale Standard Deviation 7.07

SECONDARY outcome

Timeframe: Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit

Population: The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

The severity of illness for each participant were rated using the CGI-S. To perform this assessment, the investigator were to answer the following question: "Considering your total clinical experience with this particular population, how mentally ill was the participant at that time?" Response choices include: 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	Prior Brexpiprazole n=178 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=23 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 20 (N= 20, 5, 2)	-0.55 Units on a scale Standard Deviation 0.76	0.20 Units on a scale Standard Deviation 0.45	0.00 Units on a scale Standard Deviation 0.00
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 26 (N= 19, 5, 2)	-0.63 Units on a scale Standard Deviation 0.90	0.00 Units on a scale Standard Deviation 0.71	0.00 Units on a scale Standard Deviation 0.00
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Day 4 (N= 169, 36, 22)	0.02 Units on a scale Standard Deviation 0.51	-0.03 Units on a scale Standard Deviation 0.29	0.05 Units on a scale Standard Deviation 0.38
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 1 (N= 167, 40, 23)	-0.08 Units on a scale Standard Deviation 0.47	-0.05 Units on a scale Standard Deviation 0.60	-0.04 Units on a scale Standard Deviation 0.37
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 2 (N= 164, 40, 21)	-0.12 Units on a scale Standard Deviation 0.63	-0.18 Units on a scale Standard Deviation 0.71	0.00 Units on a scale Standard Deviation 0.32
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 4 (N= 148, 34, 18)	-0.25 Units on a scale Standard Deviation 0.64	-0.24 Units on a scale Standard Deviation 0.82	-0.22 Units on a scale Standard Deviation 0.43
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 6 (N= 139, 31, 15)	-0.40 Units on a scale Standard Deviation 0.66	-0.35 Units on a scale Standard Deviation 0.80	-0.33 Units on a scale Standard Deviation 0.49
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 8 (N= 20, 6, 2)	-0.20 Units on a scale Standard Deviation 0.77	0.17 Units on a scale Standard Deviation 0.41	0.00 Units on a scale Standard Deviation 0.00
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 14 (N= 20, 6, 2)	-0.40 Units on a scale Standard Deviation 0.68	0.83 Units on a scale Standard Deviation 1.60	0.50 Units on a scale Standard Deviation 0.71
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 32 (N= 18, 5, 2)	-0.78 Units on a scale Standard Deviation 0.81	0.20 Units on a scale Standard Deviation 1.10	-0.50 Units on a scale Standard Deviation 0.71
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 38 (N= 17, 3, 2)	-0.71 Units on a scale Standard Deviation 0.85	0.00 Units on a scale Standard Deviation 0.00	-0.50 Units on a scale Standard Deviation 0.71
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 44 (N= 17, 2, 2)	-0.82 Units on a scale Standard Deviation 0.81	0.00 Units on a scale Standard Deviation 0.00	-0.50 Units on a scale Standard Deviation 0.71
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Week 52 (N= 16, 2, 2)	-0.88 Units on a scale Standard Deviation 0.81	0.00 Units on a scale Standard Deviation 0.00	-0.50 Units on a scale Standard Deviation 0.71
Change From Baseline in Clinical Global Impression- Severity of Illness Scale (CGI-S) Score. Last visit (N= 176, 41, 23)	-0.33 Units on a scale Standard Deviation 0.83	-0.15 Units on a scale Standard Deviation 1.20	-0.30 Units on a scale Standard Deviation 0.56

SECONDARY outcome

Timeframe: Baseline, Week 1, 2, 6, 26, 52 and Last Visit

Population: The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

The PSP was a validated clinician-rated scale that measured personal and social functioning in four domains: socially useful activities (e.g, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment in each of these domains was rated as absent, mild, manifest, marked, severe, or very severe. These ratings were then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater's judgment that determined the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented manifest disabilities of various degrees and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision.

Outcome measures

Measure	Prior Brexpiprazole n=178 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=23 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Change From Baseline in Personal and Social Performance Scale (PSP) Total Score. Week 1 (N= 5, 1, 1)	-2.00 Units on a scale Full Range 4.82 • Interval -10.0 to 2.0	-21.00 Units on a scale Full Range 0 • Interval -21.0 to -21.0	-5.00 Units on a scale Full Range 0 • Interval -5.0 to -5.0
Change From Baseline in Personal and Social Performance Scale (PSP) Total Score. Week 2 (N= 163, 40, 21)	1.00 Units on a scale Full Range 7.11 • Interval -23.0 to 20.0	1.50 Units on a scale Full Range 8.16 • Interval -13.0 to 30.0	0.00 Units on a scale Full Range 0.00 • Interval -6.0 to 10.0
Change From Baseline in Personal and Social Performance Scale (PSP) Total Score. Week 6 (N= 139, 31, 15)	5.00 Units on a scale Full Range 9.34 • Interval -47.0 to 35.0	6.00 Units on a scale Full Range 10.86 • Interval -10.0 to 40.0	1.00 Units on a scale Full Range 5.96 • Interval -8.0 to 16.0
Change From Baseline in Personal and Social Performance Scale (PSP) Total Score. Week 26 (N= 19, 5, 2)	6.00 Units on a scale Full Range 5.35 • Interval 0.0 to 20.0	12.00 Units on a scale Full Range 8.07 • Interval -5.0 to 14.0	2.50 Units on a scale Full Range 3.54 • Interval 0.0 to 5.0
Change From Baseline in Personal and Social Performance Scale (PSP) Total Score. Week 52 (N= 16, 2, 2)	13.00 Units on a scale Full Range 7.31 • Interval 0.0 to 30.0	13.00 Units on a scale Full Range 1.41 • Interval 12.0 to 14.0	0.50 Units on a scale Full Range 0.71 • Interval 0.0 to 1.0
Change From Baseline in Personal and Social Performance Scale (PSP) Total Score. Last visit (N= 171, 41, 22)	4.00 Units on a scale Full Range 10.28 • Interval -47.0 to 35.0	5.00 Units on a scale Full Range 15.10 • Interval -50.0 to 40.0	1.00 Units on a scale Full Range 5.32 • Interval -8.0 to 16.0

SECONDARY outcome

Timeframe: Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit

Population: The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

The efficacy of study medication was rated for each participant using the CGI-I. The investigator rated the participants total improvement whether or not it was due to the drug treatment. All responses were compared to the participants condition at Screening/Baseline (i.e, Week 6 visit of Protocol NCT00905307). 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	Prior Brexpiprazole n=178 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=23 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Last visit (N= 176, 41, 23)	3.04 Units on a scale Standard Deviation 1.14	3.32 Units on a scale Standard Deviation 1.52	2.83 Units on a scale Standard Deviation 1.19
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Day 4 (N= 169, 36, 22)	3.70 Units on a scale Standard Deviation 0.87	3.56 Units on a scale Standard Deviation 0.88	3.23 Units on a scale Standard Deviation 1.15
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 1 (N= 167, 40, 23)	3.51 Units on a scale Standard Deviation 0.89	3.73 Units on a scale Standard Deviation 0.93	3.13 Units on a scale Standard Deviation 1.14
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 2 (N= 164, 40, 21)	3.41 Units on a scale Standard Deviation 1.10	3.45 Units on a scale Standard Deviation 1.28	3.38 Units on a scale Standard Deviation 1.28
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 4 (N= 148, 34, 18)	3.14 Units on a scale Standard Deviation 1.04	3.26 Units on a scale Standard Deviation 1.21	2.94 Units on a scale Standard Deviation 1.21
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 6 (N= 139, 31, 15)	2.86 Units on a scale Standard Deviation 0.99	3.03 Units on a scale Standard Deviation 1.28	2.60 Units on a scale Standard Deviation 1.18
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 8 (N= 20, 6, 2)	2.80 Units on a scale Standard Deviation 0.95	3.50 Units on a scale Standard Deviation 1.22	3.00 Units on a scale Standard Deviation 1.41
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 14 (N= 20, 6, 2)	2.75 Units on a scale Standard Deviation 0.85	3.83 Units on a scale Standard Deviation 1.60	4.50 Units on a scale Standard Deviation 0.71
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 20 (N= 20, 5, 2)	2.70 Units on a scale Standard Deviation 1.03	3.20 Units on a scale Standard Deviation 1.30	4.00 Units on a scale Standard Deviation 0.00
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 26 (N= 19, 5, 2)	2.74 Units on a scale Standard Deviation 0.93	3.00 Units on a scale Standard Deviation 1.41	4.00 Units on a scale Standard Deviation 0.00
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 32 (N= 18, 5, 2)	2.56 Units on a scale Standard Deviation 0.78	3.20 Units on a scale Standard Deviation 1.79	3.00 Units on a scale Standard Deviation 1.41
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 38 (N= 17, 3, 2)	2.53 Units on a scale Standard Deviation 0.87	2.67 Units on a scale Standard Deviation 1.15	3.00 Units on a scale Standard Deviation 1.41
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 44 (N= 17, 2, 2)	2.35 Units on a scale Standard Deviation 0.79	3.00 Units on a scale Standard Deviation 1.41	3.00 Units on a scale Standard Deviation 1.41
Mean Clinical Global Impression- Improvement Scale (CGI-I) Total Score. Week 52 (N= 16, 2, 2)	2.31 Units on a scale Standard Deviation 0.79	3.00 Units on a scale Standard Deviation 1.41	3.00 Units on a scale Standard Deviation 1.41

SECONDARY outcome

Timeframe: Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit

Population: The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS positive symptom score ranges from 7-49, with higher scores indicating more severe symptoms.

Outcome measures

Measure	Prior Brexpiprazole n=178 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=23 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Change From Baseline in PANSS Positive Subscale Score. Week 6 (N= 138, 31, 15)	-2.36 Units on a scale Standard Deviation 3.21	-2.03 Units on a scale Standard Deviation 3.06	-1.87 Units on a scale Standard Deviation 2.39
Change From Baseline in PANSS Positive Subscale Score. Week 8 (N= 20, 6, 2)	-2.10 Units on a scale Standard Deviation 3.02	-1.67 Units on a scale Standard Deviation 2.34	-2.50 Units on a scale Standard Deviation 2.12
Change From Baseline in PANSS Positive Subscale Score. Week 14 (20, 6, 2)	-2.80 Units on a scale Standard Deviation 2.65	2.17 Units on a scale Standard Deviation 9.04	1.00 Units on a scale Standard Deviation 4.24
Change From Baseline in PANSS Positive Subscale Score. Week 20 (20, 5, 2)	-2.60 Units on a scale Standard Deviation 3.49	-1.80 Units on a scale Standard Deviation 2.39	0.00 Units on a scale Standard Deviation 4.24
Change From Baseline in PANSS Positive Subscale Score. Week 26 (N= 19, 5, 2)	-3.42 Units on a scale Standard Deviation 2.99	-2.60 Units on a scale Standard Deviation 2.61	-3.00 Units on a scale Standard Deviation 1.41
Change From Baseline in PANSS Positive Subscale Score. Week 32 (N= 18, 5, 2)	-3.83 Units on a scale Standard Deviation 3.54	-1.00 Units on a scale Standard Deviation 4.85	-5.00 Units on a scale Standard Deviation 1.41
Change From Baseline in PANSS Positive Subscale Score. Week 38 (N= 17, 3, 2)	-3.71 Units on a scale Standard Deviation 4.10	-2.67 Units on a scale Standard Deviation 2.52	-3.00 Units on a scale Standard Deviation 0.00
Change From Baseline in PANSS Positive Subscale Score. Week 44 (N= 17, 2, 2)	-4.24 Units on a scale Standard Deviation 3.53	-1.50 Units on a scale Standard Deviation 2.12	-4.00 Units on a scale Standard Deviation 1.41
Change From Baseline in PANSS Positive Subscale Score. Week 52 (N= 16, 2, 2)	-3.63 Units on a scale Standard Deviation 3.74	-1.50 Units on a scale Standard Deviation 2.12	-4.50 Units on a scale Standard Deviation 3.54
Change From Baseline in PANSS Positive Subscale Score. Last visit (N= 176, 41, 23)	-1.74 Units on a scale Standard Deviation 3.86	-0.22 Units on a scale Standard Deviation 6.04	-1.43 Units on a scale Standard Deviation 2.87
Change From Baseline in PANSS Positive Subscale Score. Day 4 (N= 169, 36, 22)	-0.04 Units on a scale Standard Deviation 2.06	-0.50 Units on a scale Standard Deviation 1.36	0.09 Units on a scale Standard Deviation 2.24
Change From Baseline in PANSS Positive Subscale Score. Week 1 (N= 167, 40, 23)	-0.66 Units on a scale Standard Deviation 1.91	-0.25 Units on a scale Standard Deviation 2.72	-0.78 Units on a scale Standard Deviation 2.76
Change From Baseline in PANSS Positive Subscale Score. Week 2 (N= 165, 40, 21)	-1.09 Units on a scale Standard Deviation 2.92	-0.70 Units on a scale Standard Deviation 3.75	-0.05 Units on a scale Standard Deviation 2.84
Change From Baseline in PANSS Positive Subscale Score. Week 4 (N= 148, 34, 18)	-1.53 Units on a scale Standard Deviation 2.96	-1.06 Units on a scale Standard Deviation 3.95	-1.11 Units on a scale Standard Deviation 2.08

SECONDARY outcome

Timeframe: Baseline, Day 4, Week 1, 2, 4, 6, 8, 14, 20, 26, 32, 38, 44, 52 and Last Visit

Population: The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In negative subscale the severity was rated for the following 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS negative symptom score ranges from 7-49, with higher scores indicating more severe symptoms.

Outcome measures

Measure	Prior Brexpiprazole n=178 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=23 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Change From Baseline in PANSS Negative Subscale Score. Week 44 (N= 17, 2, 2)	-4.18 Units on a scale Standard Deviation 3.61	-1.00 Units on a scale Standard Deviation 2.83	-2.50 Units on a scale Standard Deviation 3.54
Change From Baseline in PANSS Negative Subscale Score. Day 4 (N= 169, 36, 22)	-0.01 Units on a scale Standard Deviation 1.99	-0.25 Units on a scale Standard Deviation 1.00	-0.86 Units on a scale Standard Deviation 2.12
Change From Baseline in PANSS Negative Subscale Score. Week 1 (N= 167, 40, 23)	-0.47 Units on a scale Standard Deviation 2.15	-0.40 Units on a scale Standard Deviation 2.58	-0.87 Units on a scale Standard Deviation 2.44
Change From Baseline in PANSS Negative Subscale Score. Week 2 (N= 165, 40, 21)	-0.68 Units on a scale Standard Deviation 2.61	-0.83 Units on a scale Standard Deviation 2.32	-1.19 Units on a scale Standard Deviation 2.52
Change From Baseline in PANSS Negative Subscale Score. Week 4 (N= 148, 34, 18)	-1.03 Units on a scale Standard Deviation 2.99	-1.35 Units on a scale Standard Deviation 3.02	-1.94 Units on a scale Standard Deviation 2.48
Change From Baseline in PANSS Negative Subscale Score. Week 6 (N= 138, 31, 15)	-1.70 Units on a scale Standard Deviation 3.04	-1.97 Units on a scale Standard Deviation 2.70	-2.40 Units on a scale Standard Deviation 2.61
Change From Baseline in PANSS Negative Subscale Score. Week 8 (N= 20, 6, 2)	-2.55 Units on a scale Standard Deviation 2.68	-1.00 Units on a scale Standard Deviation 2.00	-1.00 Units on a scale Standard Deviation 1.41
Change From Baseline in PANSS Negative Subscale Score. Week 14 (N= 20, 6, 2)	-2.85 Units on a scale Standard Deviation 3.15	1.17 Units on a scale Standard Deviation 7.05	-1.50 Units on a scale Standard Deviation 2.12
Change From Baseline in PANSS Negative Subscale Score. Week 20 (N= 20, 5, 2)	-3.00 Units on a scale Standard Deviation 3.04	-0.60 Units on a scale Standard Deviation 1.14	-2.00 Units on a scale Standard Deviation 2.83
Change From Baseline in PANSS Negative Subscale Score. Week 26 (N= 19, 5, 2)	-3.74 Units on a scale Standard Deviation 3.43	-1.20 Units on a scale Standard Deviation 1.48	-2.50 Units on a scale Standard Deviation 2.12
Change From Baseline in PANSS Negative Subscale Score. Week 32 (N= 18, 5, 2)	-4.00 Units on a scale Standard Deviation 4.41	-1.00 Units on a scale Standard Deviation 1.87	-2.50 Units on a scale Standard Deviation 3.54
Change From Baseline in PANSS Negative Subscale Score. Week 38 (N= 17, 3, 2)	-3.94 Units on a scale Standard Deviation 3.93	-0.67 Units on a scale Standard Deviation 2.08	-2.50 Units on a scale Standard Deviation 3.54
Change From Baseline in PANSS Negative Subscale Score. Week 52 (N= 16, 2, 2)	-4.00 Units on a scale Standard Deviation 3.58	-1.00 Units on a scale Standard Deviation 2.83	-2.00 Units on a scale Standard Deviation 1.41
Change From Baseline in PANSS Negative Subscale Score. Last visit (N= 176, 41, 23)	-1.53 Units on a scale Standard Deviation 3.28	-1.10 Units on a scale Standard Deviation 3.85	-2.09 Units on a scale Standard Deviation 2.59

SECONDARY outcome

Timeframe: Last Visit

Population: The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

Response rate was defined as a reduction of ≥ 30% from Baseline in PANSS total score or CGI-I score of 1 (very much improved) or 2 (much improved) at the Last Visit.

Outcome measures

Measure	Prior Brexpiprazole n=179 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=24 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Percentage of Participants With a Positive Response Rate.	33.5 Percentage of participants	36.6 Percentage of participants	45.8 Percentage of participants

SECONDARY outcome

Timeframe: Last Visit

Population: The efficacy analysis dataset comprised those participants who received study medication of brexpiprazole and had at least one Post-Baseline assessment for PANSS total score.

Discontinuation rate for the participants discontinued due to lack of efficacy were examined.

Outcome measures

Measure	Prior Brexpiprazole n=179 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=24 Participants The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Percentage of Participants Who Discontinued Due to Lack of Efficacy.	2.8 Percentage of participants.	0.0 Percentage of participants.	0.0 Percentage of participants.

Adverse Events

Prior Brexpiprazole

Serious events: 4 serious events

Other events: 31 other events

Deaths: 0 deaths

Prior Placebo

Serious events: 6 serious events

Other events: 10 other events

Deaths: 0 deaths

Prior Aripiprazole

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Prior Brexpiprazole n=178 participants at risk The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 participants at risk The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=23 participants at risk The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Infections and infestations Bronchitis	0.00% 0/178 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	2.4% 1/41 • Number of events 1 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	0.00% 0/23 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.
Infections and infestations Influenza	0.00% 0/178 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	2.4% 1/41 • Number of events 1 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	0.00% 0/23 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.
Nervous system disorders Convulsion	0.00% 0/178 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	2.4% 1/41 • Number of events 1 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	0.00% 0/23 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.
Psychiatric disorders Psychotic disorder	1.1% 2/178 • Number of events 2 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	2.4% 1/41 • Number of events 1 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	4.3% 1/23 • Number of events 1 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.
Psychiatric disorders Schizophrenia	1.1% 2/178 • Number of events 2 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	7.3% 3/41 • Number of events 3 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	0.00% 0/23 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.

Other adverse events

Measure	Prior Brexpiprazole n=178 participants at risk The participants were grouped based on the medications that they received prior to the trial. The participants in prior brexpiprazole group included the participants who received brexpiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Placebo n=41 participants at risk The participants were grouped based on the medications that they received prior to the trial. The participants in prior placebo group included the participants who received placebo prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.	Prior Aripiprazole n=23 participants at risk The participants were grouped based on the medications that they received prior to the trial. The participants in prior aripiprazole group included the participants who received aripiprazole prior to the trial. The participants began dosing with brexpiprazole 2 mg daily and the dosage was increased upto 6 mg daily if the dose was well-tolerated.
Psychiatric disorders Insomnia	5.6% 10/178 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	7.3% 3/41 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	0.00% 0/23 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.
Nervous system disorders Extrapyramidal disorder	1.1% 2/178 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	2.4% 1/41 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	8.7% 2/23 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.
Nervous system disorders Headache	3.4% 6/178 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	12.2% 5/41 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	0.00% 0/23 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.
Nervous system disorders Tremor	5.1% 9/178 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	2.4% 1/41 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	0.00% 0/23 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.
Psychiatric disorders Anxiety	2.8% 5/178 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	0.00% 0/41 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.	8.7% 2/23 • AEs were recorded from Screening (ICF was signed) to Follow-up 30 (± 2) days, up to 52 weeks. The safety dataset comprised of those participants who received at least one dose of open-label brexpiprazole.

Additional Information

Global Medical Affairs

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Results disclosure agreements

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