Trial Outcomes & Findings for Study of the Effectiveness of Three Different Doses of OPC-34712 in the Treatment of Adults With Acute Schizophrenia (NCT NCT01396421)

NCT ID: NCT01396421

Last Updated: 2015-10-29

Results Overview

The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 636 participants
• Primary outcome timeframe: Baseline to Week 6
• Results posted on: 2015-10-29

Participant Flow

The trial was conducted in 636 participants from 65 trial sites in 10 countries.

Adults with schizophrenia as defined by Diagnostic and Statistical Manual of Mental Health Disorders 4th Edition Text Revision criteria and confirmed by the Mini International Neuropsychiatric Interview for schizophrenia and psychotic disorders studies.

Participant milestones

Measure	Brexpiprazole 4 mg Brexpiprazole 4 milligram (mg) tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2mg Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25mg Brexpiprazole 0.25mg tablet once daily for 6 weeks.	Placebo Placebo tablet once daily for 6 weeks.
Overall Study STARTED	180	182	90	184
Overall Study COMPLETED	121	124	56	109
Overall Study NOT COMPLETED	59	58	34	75

Reasons for withdrawal

Measure	Brexpiprazole 4 mg Brexpiprazole 4 milligram (mg) tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2mg Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25mg Brexpiprazole 0.25mg tablet once daily for 6 weeks.	Placebo Placebo tablet once daily for 6 weeks.
Overall Study Lost to Follow-up	0	0	0	1
Overall Study Adverse Event	17	15	12	32
Overall Study Participant Met Withdrawal Criteria	1	0	1	0
Overall Study Physician Decision	1	1	0	3
Overall Study Withdrawal by Subject	31	24	13	21
Overall Study Protocol Deviation	2	1	1	0
Overall Study Lack of Efficacy	7	17	7	18

Baseline Characteristics

Study of the Effectiveness of Three Different Doses of OPC-34712 in the Treatment of Adults With Acute Schizophrenia

Baseline characteristics by cohort

Measure	Brexpiprazole 4mg n=180 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2mg n=182 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=90 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks.	Placebo n=184 Participants Placebo tablet once daily for 6 weeks.	Total n=636 Participants Total of all reporting groups
Age, Continuous	40.8 Years STANDARD_DEVIATION 11.0 • n=5 Participants	39.6 Years STANDARD_DEVIATION 10.2 • n=7 Participants	40.5 Years STANDARD_DEVIATION 11.4 • n=5 Participants	39.7 Years STANDARD_DEVIATION 10.8 • n=4 Participants	40.1 Years STANDARD_DEVIATION 10.8 • n=21 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	71 Participants n=7 Participants	29 Participants n=5 Participants	66 Participants n=4 Participants	235 Participants n=21 Participants
Sex: Female, Male Male	111 Participants n=5 Participants	111 Participants n=7 Participants	61 Participants n=5 Participants	118 Participants n=4 Participants	401 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 134, 132, 62 and 124 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

Outcome measures

Measure	Brexpiprazole 4mg n=134 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=132 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=62 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=124 Participants Placebo tablet once daily for 6 weeks.
Mean Change From Baseline to Week 6 Positive and Negative Syndrome Scale (PANSS) Total Score.	-19.65 Units on a scale Standard Error 1.54	-20.73 Units on a scale Standard Error 1.55	-14.90 Units on a scale Standard Error 2.23	-12.01 Units on a scale Standard Error 1.60

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 124, 56 and 109 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

The severity of illness was rated using the CGI-S which is the key secondary endpoint. To perform this assessment, the rater or 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 participant.

Outcome measures

Measure	Brexpiprazole 4mg n=121 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=124 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=56 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=109 Participants Placebo tablet once daily for 6 weeks.
Mean Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score.	-1.20 Units on a scale Standard Error 0.08	-1.15 Units on a scale Standard Error 0.08	-0.85 Units on a scale Standard Error 0.12	-0.82 Units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline to Week 1, 2, 3, 4, 5

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation.

The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

Outcome measures

Measure	Brexpiprazole 4mg n=178 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=180 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=87 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=178 Participants Placebo tablet once daily for 6 weeks.
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. Week 1	-4.38 Units on a scale Standard Error 0.60	-4.87 Units on a scale Standard Error 0.59	-2.52 Units on a scale Standard Error 0.83	-2.87 Units on a scale Standard Error 0.60
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. Week 2	-9.51 Units on a scale Standard Error 0.93	-8.86 Units on a scale Standard Error 0.93	-3.28 Units on a scale Standard Error 1.32	-5.11 Units on a scale Standard Error 0.95
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. Week 3	-12.78 Units on a scale Standard Error 1.15	-11.08 Units on a scale Standard Error 1.16	-5.71 Units on a scale Standard Error 1.65	-7.64 Units on a scale Standard Error 1.18
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. Week 4	-16.50 Units on a scale Standard Error 1.32	-14.06 Units on a scale Standard Error 1.32	-8.86 Units on a scale Standard Error 1.90	-8.89 Units on a scale Standard Error 1.35
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. Week 5	-18.61 Units on a scale Standard Error 1.42	-17.90 Units on a scale Standard Error 1.43	-11.87 Units on a scale Standard Error 2.05	-10.75 Units on a scale Standard Error 1.47

SECONDARY outcome

Timeframe: Baseline to Week 1, 2, 3, 4 and 5

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation.

The severity of illness was rated using the CGI-S. To perform this assessment, the rater or 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 participant.

Outcome measures

Measure	Brexpiprazole 4mg n=178 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=181 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=89 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=181 Participants Placebo tablet once daily for 6 weeks.
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. Week 1	-0.16 Units on a scale Standard Error 0.04	-0.16 Units on a scale Standard Error 0.04	-0.11 Units on a scale Standard Error 0.05	-0.14 Units on a scale Standard Error 0.04
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. Week 2	-0.46 Units on a scale Standard Error 0.05	-0.43 Units on a scale Standard Error 0.05	-0.18 Units on a scale Standard Error 0.07	-0.30 Units on a scale Standard Error 0.05
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. Week 3	-0.72 Units on a scale Standard Error 0.06	-0.60 Units on a scale Standard Error 0.06	-0.33 Units on a scale Standard Error 0.09	-0.51 Units on a scale Standard Error 0.07
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. Week 4	-0.96 Units on a scale Standard Error 0.07	-0.73 Units on a scale Standard Error 0.07	-0.58 Units on a scale Standard Error 0.11	-0.54 Units on a scale Standard Error 0.08
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. Week 5	-1.08 Units on a scale Standard Error 0.08	-1.03 Units on a scale Standard Error 0.08	-0.73 Units on a scale Standard Error 0.11	-0.69 Units on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 122, 55 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

The PSP is a clinician-rated scale that measures personal and social functioning in 4 domains: socially useful activities (eg, 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 to determine 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	Brexpiprazole 4mg n=121 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=122 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=55 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=108 Participants Placebo tablet once daily for 6 weeks.
Mean Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)	12.72 Units on a scale Standard Error 0.93	13.15 Units on a scale Standard Error 0.93	11.84 Units on a scale Standard Error 1.33	10.26 Units on a scale Standard Error 0.98

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

For each symptom construct of the PANSS Positive Subscale, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The symptom constructs were as follows: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale Score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.

Outcome measures

Measure	Brexpiprazole 4mg n=121 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=123 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=56 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=108 Participants Placebo tablet once daily for 6 weeks.
Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score	-6.78 Units on a scale Standard Error 0.51	-6.57 Units on a scale Standard Error 0.52	-5.46 Units on a scale Standard Error 0.74	-4.35 Units on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

For each symptom construct of the PANSS Negative Subscale, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The symptom constructs were as follows: 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 Subscale Score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.

Outcome measures

Measure	Brexpiprazole 4mg n=121 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=123 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=56 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=108 Participants Placebo tablet once daily for 6 weeks.
Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score	-3.65 Units on a scale Standard Error 0.36	-4.02 Units on a scale Standard Error 0.36	-3.31 Units on a scale Standard Error 0.53	-2.24 Units on a scale Standard Error 0.38

SECONDARY outcome

Timeframe: Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation.

The participant's overall improvement was rated using the CGI-I. The rater or study physician rated the participant's total improvement whether or not it was due entirely to drug treatment. All responses were compared with the participant's condition at screening/baseline. Response choices were: 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 4mg n=178 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=181 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=89 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=178 Participants Placebo tablet once daily for 6 weeks.
Clinical Global Impression- Improvement Scale (CGI-I) Score at Week 6	2.94 Units on a scale Standard Deviation 1.29	2.94 Units on a scale Standard Deviation 1.34	3.37 Units on a scale Standard Deviation 1.46	3.48 Units on a scale Standard Deviation 1.47

SECONDARY outcome

Timeframe: Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation.

Response rate was defined as improvement in mean change of ≥30% from baseline in PANSS Total Score at Week 6 or CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6.

Outcome measures

Measure	Brexpiprazole 4mg n=178 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=180 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=87 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=178 Participants Placebo tablet once daily for 6 weeks.
Response Rate at Week 6	46.07 Percentage of participants	47.78 Percentage of participants	39.08 Percentage of participants	30.34 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

The PEC consists of 5 PANSS items (excitement [P4], hostility [P7], tension [G4], uncooperativeness [G8], and poor impulse control [G14]). Each rated on a scale of 1 (absent) to 7 (extreme). The PEC for participants was calculated as the sum of the rating assigned to each of the 5 items, and ranged from 5 to 35 with a higher score indicating greater severity of symptoms.

Outcome measures

Measure	Brexpiprazole 4mg n=121 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=123 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=56 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=108 Participants Placebo tablet once daily for 6 weeks.
Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score	-2.75 Units on a scale Standard Error 0.34	-2.87 Units on a scale Standard Error 0.34	-1.99 Units on a scale Standard Error 0.49	-1.64 Units on a scale Standard Error 0.36

SECONDARY outcome

Timeframe: Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation.

Outcome measures

Measure	Brexpiprazole 4mg n=178 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=180 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=87 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=178 Participants Placebo tablet once daily for 6 weeks.
Discontinuation Rate for Lack of Efficacy at Week 6	3.93 Percentage of participants	9.44 Percentage of participants	8.05 Percentage of participants	10.11 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

The PANSS Marder Factor score - Positive Symptoms Score consists of 8 PANSS items (delusions [P1], hallucinatory behaviour [P3], grandiosity [P5], suspiciousness [P6], stereotyped thinking [N7], somatic concern [G1], unusual thought content [G9], lack of judgment and insight [G10]. Each was rated on a scale of 1 (absent) to 7 (extreme). The PANSS Marder Factor score - Positive Symptoms Score for participants was calculated as the sum of the rating assigned to each of the 8 items, and ranged from 8 to 42 with a higher score indicating greater severity of symptoms.

Outcome measures

Measure	Brexpiprazole 4mg n=121 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=123 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=56 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=108 Participants Placebo tablet once daily for 6 weeks.
Change From Baseline to Week 6 in PANSS Marder Factor Score - Positive Symptoms Score	-7.23 Units on a scale Standard Error 0.51	-7.37 Units on a scale Standard Error 0.51	-5.78 Units on a scale Standard Error 0.73	-4.89 Units on a scale Standard Error 0.53

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

The PANSS Marder Factor score - Negative Symptoms Score consists of 7 PANSS items (blunted effect [N1], emotional withdrawal [N2], poor rapport [N3], passive/apathetic social withdrawal [N4], lack of spontaneity and conversation flow [N6], motor retardation [G7], active social avoidance [G16]). The PANSS Marder Factor score - Negative Symptoms Score for participants was calculated as the sum of the rating assigned to each of the 7 items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.

Outcome measures

Measure	Brexpiprazole 4mg n=121 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=123 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=56 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=108 Participants Placebo tablet once daily for 6 weeks.
Change From Baseline to Week 6 in PANSS Marder Factor Score - Negative Symptoms Score	-4.10 Units on a scale Standard Error 0.37	-4.48 Units on a scale Standard Error 0.37	-3.66 Units on a scale Standard Error 0.54	-2.80 Units on a scale Standard Error 0.38

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

The PANSS Marder Factor score -Disorganized Thought Score consists of 7 PANSS items (conceptual disorganization [P2], difficulty in abstract thinking [N5], mannerisms and posturing [G5], disorientation [G10], poor attention [G11], disturbance of violation [G13], preoccupation [G15]). The PANSS Marder Factor score - Disorganized Thought Score for participants was calculated as the sum of the rating assigned to each of the 7 items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.

Outcome measures

Measure	Brexpiprazole 4mg n=121 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=123 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=56 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=108 Participants Placebo tablet once daily for 6 weeks.
Change From Baseline to Week 6 in PANSS Marder Disorganised Thought Score	-3.72 Units on a scale Standard Error 0.36	-3.94 Units on a scale Standard Error 0.36	-2.69 Units on a scale Standard Error 0.52	-1.97 Units on a scale Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

The PANSS Marder Factor score - Uncontrolled Hostility/Excitement Score consists of 4 PANSS items (excitement [P4], hostility [P7], uncooperativeness [G8], poor impulse control [G14]). The PANSS Marder Factor score - Uncontrolled Hostility/Excitement Score for participants was calculated as the sum of the rating assigned to each of the 4 items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms.

Outcome measures

Measure	Brexpiprazole 4mg n=121 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=123 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=56 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=108 Participants Placebo tablet once daily for 6 weeks.
Change From Baseline to Week 6 in PANSS Marder Uncontrolled Hostility/Excitement Score	-1.90 Units on a scale Standard Error 0.28	-1.91 Units on a scale Standard Error 0.28	-1.15 Units on a scale Standard Error 0.41	-0.82 Units on a scale Standard Error 0.30

SECONDARY outcome

Timeframe: Baseline to Week 6

Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.

The PANSS Marder Factor score - Anxiety/Depression Score consists of 4 PANSS items (anxiety [G2], guilt feelings [G3], tension [G4], depression [G6]). The PANSS Marder Factor score - Anxiety/Depression Score for participants was calculated as the sum of the rating assigned to each of the 4 items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms.

Outcome measures

Measure	Brexpiprazole 4mg n=121 Participants Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=123 Participants Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazole 0.25 mg n=56 Participants Brexpiprazole 0.25mg tablet once daily for 6 weeks	Placebo n=108 Participants Placebo tablet once daily for 6 weeks.
Change From Baseline to Week 6 in PANSS Marder Anxiety Depression Score	-3.40 Units on a scale Standard Error 0.25	-3.70 Units on a scale Standard Error 0.25	-3.27 Units on a scale Standard Error 0.35	-3.05 Units on a scale Standard Error 0.26

Adverse Events

Brexpiprazole 4mg

Serious events: 2 serious events

Other events: 64 other events

Deaths: 0 deaths

Brexpiprazole 2 mg

Serious events: 4 serious events

Other events: 53 other events

Deaths: 0 deaths

Brexpiprazile 0.25 mg

Serious events: 4 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Measure	Brexpiprazole 4mg n=180 participants at risk Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=182 participants at risk Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazile 0.25 mg n=90 participants at risk Brexpiprazole 0.25mg tablet once daily for 6 weeks.	Placebo n=184 participants at risk Placebo tablet once daily for 6 weeks.
Cardiac disorders Acute myocardial infarction	0.00% 0/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	1.1% 1/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Gastrointestinal disorders Gastric ulcer	0.00% 0/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.54% 1/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.55% 1/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Nervous system disorders Grand mal convulsion	0.00% 0/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.54% 1/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Psychiatric disorders Psychotic disorder	0.00% 0/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.55% 1/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	1.1% 1/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	1.1% 2/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Psychiatric disorders Schizophrenia	1.1% 2/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	1.1% 2/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	2.2% 2/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	1.1% 2/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Psychiatric disorders Schizophrenia, paranoid type	0.00% 0/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.54% 1/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.

Other adverse events

Measure	Brexpiprazole 4mg n=180 participants at risk Brexpiprazole 4mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).	Brexpiprazole 2 mg n=182 participants at risk Brexpiprazole 2mg tablet once daily for 6 weeks. Participants were titrated to the target dose of brexpiprazole over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.	Brexpiprazile 0.25 mg n=90 participants at risk Brexpiprazole 0.25mg tablet once daily for 6 weeks.	Placebo n=184 participants at risk Placebo tablet once daily for 6 weeks.
Gastrointestinal disorders Diarrhoea	3.9% 7/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	1.6% 3/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	5.6% 5/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	1.6% 3/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Gastrointestinal disorders Nausea	3.3% 6/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	5.5% 10/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	1.1% 1/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	4.3% 8/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Nervous system disorders Akathisia	7.2% 13/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	4.4% 8/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	0.00% 0/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	2.2% 4/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Nervous system disorders Headache	12.2% 22/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	9.3% 17/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	10.0% 9/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	8.2% 15/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Psychiatric disorders Agitation	7.2% 13/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	6.0% 11/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	4.4% 4/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	10.3% 19/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Psychiatric disorders Insomnia	8.3% 15/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	8.8% 16/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	8.9% 8/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	9.8% 18/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Psychiatric disorders Schizophrenia	5.6% 10/180 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	3.8% 7/182 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	6.7% 6/90 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.	9.8% 18/184 • Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.

Additional Information

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Phone: 800 562-3974

Results disclosure agreements

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