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Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults with Schizophrenia.

Summary
EudraCT number	2011-005766-38
Trial protocol	PL RO
Global end of trial date	12 Feb 2015

Results information
Results version number	v1(current)
This version publication date	27 Jul 2016
First version publication date	27 Jul 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

331-10-232

ISRCTN number

US NCT number

NCT01668797

WHO universal trial number (UTN)

Sponsor organisation name

Otsuka Pharmaceutical Development & Commercialization, Inc.

Sponsor organisation address

2440 Research Boulevard, Rockville, Maryland, United States, 20850

Public contact

Mary Hobart, Otsuka Pharmaceutical Development & Commercialization, Inc., +1 240-683-3194, Mary.Hobart@otsuka-us.com

Scientific contact

Mary Hobart, Otsuka Pharmaceutical Development & Commercialization, Inc., +1 240-683-3194, Mary.Hobart@otsuka-us.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Interim

Date of interim/final analysis

26 Jun 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

12 Feb 2015

Global end of trial reached?

Yes

Global end of trial date

12 Feb 2015

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study was to evaluate the efficacy of brexpiprazole compared with placebo as maintenance treatment in adults with schizophrenia.

Protection of trial subjects

This trial was conducted in compliance with the protocol, ICH-GCP and applicable local laws and regulatory requirements. Written informed consent was obtained from all participants (or their guardian or legal representative, as applicable according to local laws). Informed consent was obtained and documented prior to initiation of any procedures that were performed solely for the purpose of determining eligibility for this trial, including withdrawal from current medication(s). Participants were asked to sign a separate ICF designed for the purpose of collecting a onetime blood sample for assessment of cytochrome P450 (CYP) 2D6 metabolizer genotype. Participants were informed that they would not be excluded from the treatment trial if they did not wish to participate in the pharmacogenomic assessments.

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Oct 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Colombia: 61

Country: Number of subjects enrolled

Malaysia: 47

Country: Number of subjects enrolled

Puerto Rico: 38

Country: Number of subjects enrolled

Serbia: 78

Country: Number of subjects enrolled

Turkey: 18

Country: Number of subjects enrolled

Ukraine: 147

Country: Number of subjects enrolled

United States: 204

Country: Number of subjects enrolled

Romania: 73

Worldwide total number of subjects

666

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

666

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

A total of 753 participants were screened at 49 trial sites.

Screening details

Trial had Phase A (Conversion) (N= 406), Phase B (Oral Stabilization) (N= 464; 346 rolled over from Phase A and 118 entered directly into Phase B ) and Phase C (Double-Blind Maintenance) with (N= 202 rolled over from Phase B). Participants were randomized in to Phase C in a 1:1 ratio (brexpiprazole: placebo) to receive treatment for up to 52 weeks.

Period 1 title

Phase A and Phase B

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Phase A (Conversion Phase)

Arm description

The purpose of the open-label conversion phase was 2-fold: 1) to cross-titrate the participants current antipsychotic treatment to brexpiprazole monotherapy over a period of 1 to 4 weeks and 2) to allow washout of prohibited medications in preparation for the stabilization phase.

Arm type

Experimental

Investigational medicinal product name

Brexpiprazole

Investigational medicinal product code

Other name

OPC-34712

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

All participants in the Conversion phase received brexpiprazole 1 mg/day as a starting dose and the dose was adjusted within the range of brexpiprazole 1 to 4 mg/day according to the study physician's judgment.

Phase B (Stabilization Phase)

Arm description

This single-blind stabilization phase was to titrate participants to a dose of brexpiprazole (1 to 4 mg/day) that would maintain stability of psychotic symptoms over 12 consecutive weeks (within a maximum of 36 weeks), while minimizing tolerability issues.

Arm type

Experimental

Investigational medicinal product name

Brexpiprazole

Investigational medicinal product code

Other name

OPC-34712

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

All participants in this stabilization phase were titrated to a dose of brexpiprazole (1 to 4 mg/day) that would maintain stability of psychotic symptoms over 12 consecutive weeks (within a maximum of 36 weeks), while minimizing tolerability issues.

Number of subjects in period 1	Phase A (Conversion Phase)	Phase B (Stabilization Phase)
Started	406	464
Completed	346	202
Not completed	60	262
Physician decision	2	11
Consent withdrawn by subject	16	60
Terminated Study on Interim Analysis	19	86
Adverse Event Without Impending Relapse	8	43
Met withdrawal criteria	3	22
Lost to follow-up	3	16
Protocol deviation	2	3
Lack of efficacy	7	21

Period 2 title

Phase C

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

The randomized treatments were administered in a double-blind fashion with blocks of randomization numbers assigned to trial centers by the Interactive voice response system (IVRS)/ Interactive web response system (IWRS).

Are arms mutually exclusive

Yes

Phase C - Brexpiprazole (Double-Blind Maintenance Phase)

Arm description

Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.

Arm type

Experimental

Investigational medicinal product name

Brexpiprazole

Investigational medicinal product code

Other name

OPC-34712

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.

Phase C - Placebo (Double-Blind Maintenance Phase)

Arm description

Participants received placebo orally once daily for 52 weeks.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received placebo orally once daily for 52 weeks.

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Period 1 is not baseline period as it consisted of Phase A and Phase B. Phase A was for conversion from other antipsychotics to oral brexpiprazole and washout of prohibited concomitant medications, if applicable. In addition, Phase B was a single-blind treatment phase to stabilize participants on oral brexpiprazole.

Number of subjects in period 2 ^[2] ^[3]	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Started	97	105
Completed	14	9
Not completed	83	96
Physician decision	5	2
Consent withdrawn by subject	3	5
Terminated Study on Interim Analysis	49	38
Adverse Event Without Impending Relapse	4	2
Met withdrawal criteria	3	3
Lost to follow-up	4	6
Lack of Efficacy without AE	11	30
Protocol deviation	2	-
Lack of efficacy	2	10

Notes
[2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: All participants who signed the informed consent for the trial and entered the conversion phase or stabilization phase were included in the subjects enrolled per country table. However, the baseline period (Phase C) are those participants who were randomized to receive at least one dose of double-blind study medication in the maintenance phase.
[3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: 346 participants entered Phase B; 346 rolled over from Phase A and 118 new patients entered into Phase B directly.

Baseline characteristics

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Reporting group title

Phase C - Brexpiprazole (Double-Blind Maintenance Phase)

Reporting group description

Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.

Reporting group title

Phase C - Placebo (Double-Blind Maintenance Phase)

Reporting group description

Participants received placebo orally once daily for 52 weeks.

Reporting group values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)	Total
Number of subjects	97	105	202
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	97	105	202
From 65-84 years	0	0	0
85 years and over	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	38.8 ( 10.7 )	41.6 ( 10.6 )	-
Gender categorical
Units: Subjects
Female	39	40	79
Male	58	65	123

End points

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Reporting group title

Phase A (Conversion Phase)

Reporting group description

Reporting group title

Phase B (Stabilization Phase)

Reporting group description

Reporting group title

Phase C - Brexpiprazole (Double-Blind Maintenance Phase)

Reporting group description

Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.

Reporting group title

Phase C - Placebo (Double-Blind Maintenance Phase)

Reporting group description

Participants received placebo orally once daily for 52 weeks.

Primary: Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.

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End point title

Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.

End point description

The primary efficacy variable was time to impending relapse from randomization, as assessed by Clinical Global Impression of Improvement (CGI-I) score ≥5, Positive and Negative Syndrome Scale (PANSS) scores for hostility or uncooperativeness ≥5, or ≥20% increase in PANSS Total Score. Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score > 4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content). OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of "yes" to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.

End point type

Primary

End point timeframe

From randomization to time of exacerbation of psychotic symptoms/impending relapse - up to 52 weeks

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Days
number (not applicable)	169	111

Statistical analysis 1

Statistical analysis description

The total number of exacerbation of psychotic symptoms/impending relapse was estimated using a 1:1 (brexpiprazole: placebo) randomization ratio. For the primary endpoint, a 95% confidence interval for the hazard ratio (brexpiprazole vs. placebo) was provided using the Cox Proportional Hazard model with term of treatment in the model.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[1]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.292

Confidence interval

level

95%

sides

2-sided

lower limit

0.156

upper limit

0.548

Notes
[1] - The log-rank test was based on time to exacerbation of psychotic symptoms/impending relapse.

Secondary: Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance Phase

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End point title

Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance Phase

End point description

Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score > 4 with an absolute increase of ≥ 2 on that specific item or an increase on any of the following individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual though content) to a score of >4 and an absolute increase of ≥ 4 on the combined 4 PANSS items. OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Current suicidal behavior as assessed by the C-SSRS (ie, an answer of "yes" to any of the questions on the suicidal behavior section of the C-SSRS 5) Violent or aggressive behavior resulting in clinically significant self-injury to another person, or property damage.

End point type

Secondary

End point timeframe

Baseline and Week 52/Early Termination

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: percentage of participants
number (not applicable)	13.54	38.46

Statistical analysis 1

Statistical analysis description

The percentage of participants with impending relapse in treatment groups (Brexpiprazole and placebo) in final analysis for participants meeting at least one of the criteria.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Chi-squared

Confidence interval

Secondary: Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis

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End point title

Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis

End point description

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The anxiety/depression factor score is the sum of score from the 4 items on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome).

End point type

Secondary

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6 (N= 81, 84)	0.19 ( 0.25 )	0.66 ( 0.24 )
Week 12 (N= 73, 68)	0.54 ( 0.29 )	0.78 ( 0.29 )
Week 24 (N= 50, 36)	0.61 ( 0.28 )	0.58 ( 0.32 )
Week 36 (N= 33, 24)	0.46 ( 0.33 )	0.71 ( 0.39 )
Week 52 (N= 15, 9)	0.04 ( 0.43 )	0.28 ( 0.56 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.164

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-1.14

upper limit

0.19

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5466

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

0.55

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9417

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.81

upper limit

0.87

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6257

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-1.25

upper limit

0.76

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7437

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-1.68

upper limit

1.21

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4506

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.62

upper limit

0.28

Other pre-specified: Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase

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End point title

Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase

End point description

Participants were assessed for stability using the following criteria:1) Outpatient status AND 2) Positive and Negative Syndrome Scale (PANSS) Total Score ≤ 70 AND 3) A score of ≤ 4 (moderate) on each of the following PANSS items (possible scores of 1 to 7 for each item): conceptual disorganization, suspiciousness hallucinatory behavior, unusual thought content, AND 4) Clinical Global Impression - Severity of Illness scale(CGI-S) score ≤ 4 (moderately ill) AND 5) No current suicidal behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS), defined as the following: An answer of "no" to each question on the Suicidal Behavior section of the C-SSRS AND an answer of "no" to Questions 4 and 5 on the Suicidal Ideation section of the C-SSRS, if completed, AND 6) No evidence of aggressive or violent behavior resulting in clinically significant self-injury, injury to another person, property damage.

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: percentage of participants
number (not applicable)
Week 6 (N= 81, 84)	92.59	86.9
Week 12 (N= 73, 68)	93.15	86.76
Week 24 (N= 50, 36)	96	94.44
Week 36 (N= 33, 24)	93.94	83.33
Week 52 (N= 15, 9)	86.67	88.89

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2296

Method

Chi-squared

Confidence interval

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2051

Method

Chi-squared

Confidence interval

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7354

Method

Chi-squared

Confidence interval

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1977

Method

Chi-squared

Confidence interval

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8734

Method

Chi-squared

Confidence interval

Other pre-specified: Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis

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End point title

Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis

End point description

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

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6 (N= 81, 84)	0.79 ( 1.31 )	4.09 ( 1.27 )
Week 12 (N= 73, 68)	0.84 ( 1.73 )	6.15 ( 1.74 )
Week 24 (N= 50, 36)	-1.88 ( 1.39 )	2.89 ( 1.55 )
Week 36 (N= 33, 24)	-2.71 ( 1.48 )	3.33 ( 1.7 )
Week 52 (N= 15, 9)	0.61 ( 3.34 )	6.92 ( 4.53 )

Statistical analysis at Week 6

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0664

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.82

upper limit

0.23

Statistical analysis at Week 12

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0301

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.31

Confidence interval

level

95%

sides

2-sided

lower limit

-10.1

upper limit

-0.52

Statistical analysis at Week 24

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0226

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-4.77

Confidence interval

level

95%

sides

2-sided

lower limit

-8.86

upper limit

-0.68

Statistical analysis at Week 36

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0086

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.03

Confidence interval

level

95%

sides

2-sided

lower limit

-10.5

upper limit

-1.59

Statistical analysis at Week 52

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.28

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-6.31

Confidence interval

level

95%

sides

2-sided

lower limit

-18.1

upper limit

5.46

Statistical analysis at across visits

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0011

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-4.42

Confidence interval

level

95%

sides

2-sided

lower limit

-7.01

upper limit

-1.82

Other pre-specified: Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis

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End point title

Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis

End point description

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6	0.51 ( 1.4 )	3.56 ( 1.28 )
Week 12	1.55 ( 1.77 )	6.6 ( 1.62 )
Week 24	1.58 ( 1.88 )	9.17 ( 1.72 )
Week 36	2.49 ( 1.89 )	10.51 ( 1.73 )
Week 52	3.25 ( 1.94 )	11.2 ( 1.77 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0683

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.04

Confidence interval

level

95%

sides

2-sided

lower limit

-6.31

upper limit

0.23

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0174

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-5.05

Confidence interval

level

95%

sides

2-sided

lower limit

-9.2

upper limit

-0.9

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-7.59

Confidence interval

level

95%

sides

2-sided

lower limit

-12

upper limit

-3.18

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-8.02

Confidence interval

level

95%

sides

2-sided

lower limit

-12.4

upper limit

-3.59

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0007

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-7.95

Confidence interval

level

95%

sides

2-sided

lower limit

-12.5

upper limit

-3.41

Other pre-specified: Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis

End point description

PANSS consisted of three subscales: a total of 30 symptom constructs. For each construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6 (N= 81, 84)	0.17 ( 0.42 )	1.28 ( 0.41 )
Week 12 (N= 73, 68)	-0.06 ( 0.5 )	1.81 ( 0.51 )
Week 24 (N= 50, 36)	-0.84 ( 0.46 )	0.72 ( 0.51 )
Week 36 (N= 33, 24)	-0.97 ( 0.44 )	0.91 ( 0.51 )
Week 52 (N= 15, 9)	-1.21 ( 0.73 )	1.5 ( 0.99 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Placebo (Double-Blind Maintenance Phase) v Phase C - Brexpiprazole (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0507

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.11

Confidence interval

level

95%

sides

2-sided

lower limit

-2.23

upper limit

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.87

Confidence interval

level

95%

sides

2-sided

lower limit

-3.24

upper limit

-0.5

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0215

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.56

Confidence interval

level

95%

sides

2-sided

lower limit

-2.89

upper limit

-0.24

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0053

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.88

Confidence interval

level

95%

sides

2-sided

lower limit

-3.19

upper limit

-0.58

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0339

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.71

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

-0.22

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.32

upper limit

-0.88

Other pre-specified: Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis

End point description

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6	0.3 ( 0.49 )	1.25 ( 0.45 )
Week 12	0.38 ( 0.59 )	2.24 ( 0.54 )
Week 24	0.49 ( 0.64 )	3.23 ( 0.59 )
Week 36	0.97 ( 0.63 )	3.91 ( 0.58 )
Week 52	0.99 ( 0.64 )	4.17 ( 0.59 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1093

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.94

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

0.21

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0089

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.86

Confidence interval

level

95%

sides

2-sided

lower limit

-3.25

upper limit

-0.47

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.74

Confidence interval

level

95%

sides

2-sided

lower limit

-4.26

upper limit

-1.22

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.94

Confidence interval

level

95%

sides

2-sided

lower limit

-4.43

upper limit

-1.44

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.18

Confidence interval

level

95%

sides

2-sided

lower limit

-4.7

upper limit

-1.66

Other pre-specified: Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis

End point description

The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS negative subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6 (N= 81, 84)	-0.04 ( 0.37 )	0.65 ( 0.35 )
Week 12 (N= 73, 68)	-0.22 ( 0.43 )	0.55 ( 0.44 )
Week 24 (N= 50, 36)	-0.78 ( 0.39 )	0.18 ( 0.42 )
Week 36 (N= 33, 24)	-1.03 ( 0.47 )	0.02 ( 0.53 )
Week 52 (N= 15, 9)	1.3 ( 1.37 )	0.87 ( 1.71 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.165

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-1.66

upper limit

0.29

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.78

Confidence interval

level

95%

sides

2-sided

lower limit

-1.97

upper limit

0.42

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0939

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.95

Confidence interval

level

95%

sides

2-sided

lower limit

-2.07

upper limit

0.16

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1396

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.05

Confidence interval

level

95%

sides

2-sided

lower limit

-2.44

upper limit

0.35

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.847

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-4.14

upper limit

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2258

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-1.24

upper limit

0.3

Other pre-specified: Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis

End point description

The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS negative subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6	-0.12 ( 0.39 )	0.63 ( 0.35 )
Week 12	-0.17 ( 0.46 )	1.06 ( 0.42 )
Week 24	-0.08 ( 0.49 )	1.47 ( 0.44 )
Week 36	-0.14 ( 0.51 )	1.44 ( 0.46 )
Week 52	0.39 ( 0.54 )	1.63 ( 0.49 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0981

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-1.65

upper limit

0.14

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0264

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.22

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

-0.15

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0078

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.55

Confidence interval

level

95%

sides

2-sided

lower limit

-2.69

upper limit

-0.42

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0101

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.57

Confidence interval

level

95%

sides

2-sided

lower limit

-2.77

upper limit

-0.38

Statistical analysis at Week 52

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0516

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.24

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

0.01

Other pre-specified: Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis

Top of page

End point title

Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis

End point description

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

End point type

Other pre-specified

End point timeframe

Weeks 2, 12, 24, 26 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6 (N= 81, 84)	-0.01 ( 0.09 )	0.26 ( 0.09 )
Week 12 (N= 73, 68)	-0.01 ( 0.11 )	0.37 ( 0.11 )
Week 24 (N= 50, 36)	-0.16 ( 0.1 )	0.21 ( 0.1 )
Week 36 (N= 33, 24)	-0.31 ( 0.11 )	0.25 ( 0.12 )
Week 52 (N= 15, 9)	-0.23 ( 0.17 )	0.28 ( 0.22 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0279

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.53

upper limit

-0.03

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0117

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.68

upper limit

-0.09

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0105

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-0.64

upper limit

-0.09

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0007

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.56

Confidence interval

level

95%

sides

2-sided

lower limit

-0.87

upper limit

-0.25

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.078

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

0.06

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

-0.15

Other pre-specified: Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis

Top of page

End point title

Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis

End point description

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6	-0.08 ( 0.09 )	0.17 ( 0.09 )
Week 12	-0.04 ( 0.11 )	0.32 ( 0.1 )
Week 24	-0.03 ( 0.11 )	0.47 ( 0.1 )
Week 36	0 ( 0.11 )	0.56 ( 0.1 )
Week 52	0.02 ( 0.11 )	0.55 ( 0.11 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0284

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.03

Statistical analysis at Week 12.

Comparison groups

Phase C - Placebo (Double-Blind Maintenance Phase) v Phase C - Brexpiprazole (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0056

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-0.62

upper limit

-0.11

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

-0.24

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.56

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

-0.3

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0002

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-0.79

upper limit

-0.26

Other pre-specified: Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis

Top of page

End point title

Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis

End point description

The rater or investigator would rate the participant's total improvement whether or not it is due entirely to study treatment. During Phase B, responses were compared to the participant's condition at Baseline of Phase B (for participants who entered Phase B directly after screening) or to the End of Phase A visit (for participants who participated in Phase A). During Phase C, responses were compared to the participant's condition at the End of Phase B visit. Response choices include: 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.

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
arithmetic mean (standard deviation)
Week 6	3.68 ( 0.98 )	4 ( 1.14 )
Week 12	3.66 ( 1.19 )	4.1 ( 1.3 )
Week 24	3.67 ( 1.27 )	4.3 ( 1.32 )
Week 36	3.71 ( 1.27 )	4.39 ( 1.3 )
Week 52	3.77 ( 1.26 )	4.4 ( 1.32 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0387

Method

Cochran-Mantel-Haenszel

Parameter type

Mean difference (final values)

Point estimate

-0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

-0.2

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0185

Method

Cochran-Mantel-Haenszel

Parameter type

Mean difference (final values)

Point estimate

-0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-0.75

upper limit

-0.07

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Cochran-Mantel-Haenszel

Parameter type

Mean difference (final values)

Point estimate

-0.61

Confidence interval

level

95%

sides

2-sided

lower limit

-0.97

upper limit

-0.24

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

Cochran-Mantel-Haenszel

Parameter type

Mean difference (final values)

Point estimate

-0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-1.02

upper limit

-0.3

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0009

Method

Cochran-Mantel-Haenszel

Parameter type

Mean difference (final values)

Point estimate

-0.61

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

-0.25

Other pre-specified: Mean Change From Baseline in Personal and Social Performance (PSP) Scale Score - MMRM Analysis

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End point title

Mean Change From Baseline in Personal and Social Performance (PSP) Scale Score - MMRM Analysis

End point description

The PSP is a validated clinician-rated scale that measures 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 is rated as absent, mild, manifest, marked, severe, or very severe. These ratings are 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 are considered to have mild functional difficulty. Scores of 31 to 70 represent manifest disabilities of various degrees and ratings of 1 to 30 indicate minimal functioning that requires intense support and/or supervision. The PSP score ranges from 0 to 100, with higher scores indicating higher levels of social functioning.

End point type

Other pre-specified

End point timeframe

Weeks 24 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 24 (N= 50, 36)	18.85 ( 1.51 )	17.84 ( 1.82 )
Week 52 (N= 15, 9)	18.63 ( 2.76 )	12.55 ( 3.48 )

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6525

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

-3.47

upper limit

5.49

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1677

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

6.08

Confidence interval

level

95%

sides

2-sided

lower limit

-2.71

upper limit

14.87

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2347

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.55

Confidence interval

level

95%

sides

2-sided

lower limit

-2.41

upper limit

9.5

Other pre-specified: Mean Change From Baseline in PSP Scale Score - LOCF Analysis

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End point title

Mean Change From Baseline in PSP Scale Score - LOCF Analysis

End point description

End point type

Other pre-specified

End point timeframe

Weeks 24 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	94	100
Units: Units on a scale
least squares mean (standard error)
Week 24	15.2 ( 1.41 )	11.41 ( 1.32 )
Week 52	15.06 ( 1.43 )	10.31 ( 1.34 )

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

194

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0285

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

7.17

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

194

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0071

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

4.75

Confidence interval

level

95%

sides

2-sided

lower limit

1.31

upper limit

8.18

Other pre-specified: Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis

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End point title

Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis

End point description

The GAF is a clinician-rated scale that assesses the participant's psychological, social, and occupational functioning on a hypothetical continuum of mental health-illness using a scale that ranges from 1 to 100 score, where lower values indicate worst outcome. From among 10 descriptive anchors, investigators will choose the anchor which is the most representative of the participant's level of functioning at the time of the assessment and will assign a single score within the point range given for the selected anchor.

End point type

Other pre-specified

End point timeframe

Weeks 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 12 (N= 73, 68)	1.59 ( 1.27 )	-0.03 ( 1.29 )
Week 24 (N= 50, 36)	3.74 ( 1.42 )	1.09 ( 1.57 )
Week 36 (N= 33, 24)	4.71 ( 1.5 )	0.21 ( 1.67 )
Week 52 (N= 15, 9)	5.72 ( 1.87 )	-0.16 ( 2.37 )

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.329

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

-1.65

upper limit

4.88

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1756

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.66

Confidence interval

level

95%

sides

2-sided

lower limit

-1.22

upper limit

6.54

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0331

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

4.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

8.63

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0522

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

5.88

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

11.82

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0281

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

3.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

6.92

Other pre-specified: Mean Change From Baseline in GAF Scale Score - LOCF Analysis

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End point title

Mean Change From Baseline in GAF Scale Score - LOCF Analysis

End point description

End point type

Other pre-specified

End point timeframe

Weeks 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	95	102
Units: Units on a scale
least squares mean (standard error)
Week 12	0.44 ( 1.26 )	-3.44 ( 1.17 )
Week 24	0.85 ( 1.37 )	-4.51 ( 1.27 )
Week 36	0.97 ( 1.35 )	-5.84 ( 1.25 )
Week 52	0.55 ( 1.38 )	-6.01 ( 1.28 )

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0111

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

6.86

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0014

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.36

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

8.62

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

6.81

Confidence interval

level

95%

sides

2-sided

lower limit

3.61

upper limit

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

6.55

Confidence interval

level

95%

sides

2-sided

lower limit

3.28

upper limit

9.83

Other pre-specified: Percentage of Participants Who Discontinued Due to All Causes

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End point title

Percentage of Participants Who Discontinued Due to All Causes

End point description

Analysis of the percentage of participants who discontinued due to all causes was based on all participants who have been randomized and taken one dose of IMP in the Double-blind Maintenance phase. The trial was completed by sponsor when efficacy was demonstrated at the first pre-specified interim analysis (45 impending relapse events) performed by an independent (unblinded) statistician.

End point type

Other pre-specified

End point timeframe

Baseline to Week 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Percentage of participants
number (not applicable)	34.38	54.81

Statistical analysis 1

Statistical analysis description

Statistical analysis for participants who discontinued due to all causes.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0014

Method

Logrank

Confidence interval

Other pre-specified: Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis

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End point title

Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis

End point description

The PEC score consisted of five PANSS items: excitement (P4), hostility (P7), tension (G4), uncooperativeness (G8), and poor impulse control (G14). Each of the items were rated on a scale of 1 (absent) to 7 (extreme). The PEC scores ranged from 5 (not present) to 35 (extremely severe).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6 (N= 81, 84)	0.32 ( 0.23 )	0.74 ( 0.22 )
Week 12 (N= 73, 68)	0.5 ( 0.34 )	1.16 ( 0.35 )
Week 24 (N= 50, 36)	-0.06 ( 0.31 )	0.45 ( 0.36 )
Week 36 (N= 33, 24)	0.1 ( 0.33 )	1.25 ( 0.4 )
Week 52 (N= 15, 9)	-0.04 ( 0.46 )	1 ( 0.59 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1577

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-1.02

upper limit

0.17

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1685

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-1.61

upper limit

0.28

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2815

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.43

upper limit

0.42

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0286

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.14

Confidence interval

level

95%

sides

2-sided

lower limit

-2.16

upper limit

-0.12

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1803

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-2.58

upper limit

0.51

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0077

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-1.12

upper limit

-0.17

Other pre-specified: Mean Change From Baseline in PEC Score - LOCF Analysis

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End point title

Mean Change From Baseline in PEC Score - LOCF Analysis

End point description

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6	0.38 ( 0.27 )	0.81 ( 0.25 )
Week 12	0.73 ( 0.36 )	1.36 ( 0.33 )
Week 24	0.78 ( 0.42 )	1.86 ( 0.38 )
Week 36	0.89 ( 0.41 )	2.23 ( 0.38 )
Week 52	0.82 ( 0.41 )	2.35 ( 0.38 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1852

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-1.06

upper limit

0.21

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.143

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

0.21

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0323

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.08

Confidence interval

level

95%

sides

2-sided

lower limit

-2.06

upper limit

-0.09

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0071

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.34

Confidence interval

level

95%

sides

2-sided

lower limit

-2.31

upper limit

-0.37

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0023

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.54

Confidence interval

level

95%

sides

2-sided

lower limit

-2.52

upper limit

-0.56

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis

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End point title

Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis

End point description

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6 (N= 81, 84)	-0.1 ( 0.45 )	1.24 ( 0.44 )
Week 12 (N= 73, 68)	-0.18 ( 0.58 )	1.83 ( 0.58 )
Week 24 (N= 50, 36)	-0.82 ( 0.54 )	0.77 ( 0.6 )
Week 36 (N= 33, 24)	-1.35 ( 0.57 )	0.93 ( 0.63 )
Week 52 (N= 15, 9)	-1.62 ( 0.83 )	1.78 ( 1.05 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0288

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.34

Confidence interval

level

95%

sides

2-sided

lower limit

-2.54

upper limit

-0.14

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0128

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.02

Confidence interval

level

95%

sides

2-sided

lower limit

-3.6

upper limit

-0.44

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0462

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.59

Confidence interval

level

95%

sides

2-sided

lower limit

-3.15

upper limit

0.03

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0074

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.29

Confidence interval

level

95%

sides

2-sided

lower limit

-3.94

upper limit

-0.64

Statistical analysis at Week 52

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0136

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-6.05

upper limit

-0.75

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.91

Confidence interval

level

95%

sides

2-sided

lower limit

-2.84

upper limit

-0.97

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis

End point description

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6	0.05 ( 0.5 )	1.13 ( 0.46 )
Week 12	0.1 ( 0.61 )	2.03 ( 0.56 )
Week 24	0.25 ( 0.66 )	3.08 ( 0.61 )
Week 36	0.6 ( 0.66 )	3.69 ( 0.6 )
Week 52	0.58 ( 0.66 )	4.02 ( 0.6 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Placebo (Double-Blind Maintenance Phase) v Phase C - Brexpiprazole (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0695

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.08

Confidence interval

level

95%

sides

2-sided

lower limit

-2.26

upper limit

0.09

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0089

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.93

Confidence interval

level

95%

sides

2-sided

lower limit

-3.38

upper limit

-0.49

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.83

Confidence interval

level

95%

sides

2-sided

lower limit

-4.39

upper limit

-1.27

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.09

Confidence interval

level

95%

sides

2-sided

lower limit

-4.63

upper limit

-1.54

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.44

Confidence interval

level

95%

sides

2-sided

lower limit

-4.99

upper limit

-1.89

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis

End point description

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6 (N= 81, 84)	0.02 ( 0.38 )	0.68 ( 0.36 )
Week 12 (N= 73, 68)	-0.01 ( 0.45 )	0.8 ( 0.45 )
Week 24 (N= 50, 36)	-0.71 ( 0.4 )	0.46 ( 0.43 )
Week 36 (N= 33, 24)	-0.8 ( 0.5 )	0.7 ( 0.56 )
Week 52 (N= 15, 9)	1.37 ( 1.39 )	1.06 ( 1.77 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1969

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-1.66

upper limit

0.35

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2007

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.04

upper limit

0.43

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0436

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.17

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

-0.03

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0444

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.51

Confidence interval

level

95%

sides

2-sided

lower limit

-2.97

upper limit

-0.04

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8927

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

5.02

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2154

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.52

Confidence interval

level

95%

sides

2-sided

lower limit

-1.34

upper limit

0.31

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis

End point description

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6	-0.24 ( 0.4 )	0.61 ( 0.36 )
Week 12	-0.15 ( 0.48 )	1.09 ( 0.43 )
Week 24	-0.09 ( 0.49 )	1.5 ( 0.44 )
Week 36	-0.07 ( 0.52 )	1.56 ( 0.47 )
Week 52	0.34 ( 0.56 )	1.57 ( 0.5 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0707

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.85

Confidence interval

level

95%

sides

2-sided

lower limit

-1.78

upper limit

0.07

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0276

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.24

Confidence interval

level

95%

sides

2-sided

lower limit

-2.35

upper limit

-0.14

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0065

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.59

Confidence interval

level

95%

sides

2-sided

lower limit

-2.72

upper limit

-0.45

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0085

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.63

Confidence interval

level

95%

sides

2-sided

lower limit

-2.84

upper limit

-0.42

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.063

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.23

Confidence interval

level

95%

sides

2-sided

lower limit

-2.52

upper limit

0.07

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis

End point description

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6 (N= 81, 84)	-0.18 ( 0.31 )	0.32 ( 0.3 )
Week 12 (N= 73, 68)	-0.44 ( 0.38 )	0.69 ( 0.39 )
Week 24 (N= 50, 36)	-1.26 ( 0.34 )	0.27 ( 0.38 )
Week 36 (N= 33, 24)	-1.31 ( 0.44 )	0.17 ( 0.5 )
Week 52 (N= 15, 9)	-0.37 ( 0.99 )	-0.3 ( 1.24 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Placebo (Double-Blind Maintenance Phase) v Phase C - Brexpiprazole (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2251

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-1.33

upper limit

0.31

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0368

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.13

Confidence interval

level

95%

sides

2-sided

lower limit

-2.19

upper limit

-0.07

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0024

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.53

Confidence interval

level

95%

sides

2-sided

lower limit

-2.51

upper limit

-0.56

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0293

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.48

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

-0.15

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9632

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-3.32

upper limit

3.17

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0029

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.99

Confidence interval

level

95%

sides

2-sided

lower limit

-1.63

upper limit

-0.34

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis

End point description

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6	-0.32 ( 0.34 )	0.33 ( 0.31 )
Week 12	-0.19 ( 0.41 )	1.19 ( 0.38 )
Week 24	-0.29 ( 0.44 )	1.76 ( 0.41 )
Week 36	0 ( 0.45 )	1.95 ( 0.42 )
Week 52	0.29 ( 0.48 )	1.97 ( 0.45 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1062

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-1.44

upper limit

0.14

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0051

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.37

Confidence interval

level

95%

sides

2-sided

lower limit

-2.33

upper limit

-0.42

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.05

Confidence interval

level

95%

sides

2-sided

lower limit

-3.08

upper limit

-1.01

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.94

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-0.89

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0035

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.69

Confidence interval

level

95%

sides

2-sided

lower limit

-2.81

upper limit

-0.56

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis

End point description

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6 (N= 81, 84)	0.19 ( 0.19 )	0.55 ( 0.18 )
Week 12 (N= 73, 68)	0.33 ( 0.28 )	0.82 ( 0.29 )
Week 24 (N= 50, 36)	-0.26 ( 0.27 )	0.81 ( 0.31 )
Week 36 (N= 33, 24)	-0.13 ( 0.29 )	0.94 ( 0.34 )
Week 52 (N= 15, 9)	-0.2 ( 0.4 )	0.94 ( 0.5 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1465

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-0.85

upper limit

0.13

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2154

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-1.27

upper limit

0.29

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2696

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-1.23

upper limit

0.35

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0179

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.07

Confidence interval

level

95%

sides

2-sided

lower limit

-1.95

upper limit

-0.19

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0875

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.14

Confidence interval

level

95%

sides

2-sided

lower limit

-2.46

upper limit

0.18

Statistical analysis at across visits.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0021

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-1.08

upper limit

-0.24

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis

Top of page

End point title

Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis

End point description

Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome).

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6	0.32 ( 0.22 )	0.65 ( 0.21 )
Week 12	0.52 ( 0.3 )	0.94 ( 0.28 )
Week 24	0.5 ( 0.36 )	1.31 ( 0.33 )
Week 36	0.57 ( 0.36 )	1.63 ( 0.33 )
Week 52	0.49 ( 0.37 )	1.75 ( 0.34 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2135

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.86

upper limit

0.19

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2437

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.42

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

0.29

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0635

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.81

Confidence interval

level

95%

sides

2-sided

lower limit

-1.66

upper limit

0.05

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0144

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.07

Confidence interval

level

95%

sides

2-sided

lower limit

-1.92

upper limit

-0.22

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0046

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.26

Confidence interval

level

95%

sides

2-sided

lower limit

-2.12

upper limit

-0.39

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis

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End point title

Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis

End point description

End point type

Other pre-specified

End point timeframe

Weeks 6, 12, 24, 36 and 52

End point values	Phase C - Brexpiprazole (Double-Blind Maintenance Phase)	Phase C - Placebo (Double-Blind Maintenance Phase)
Number of subjects analysed	96	104
Units: Units on a scale
least squares mean (standard error)
Week 6	0.19 ( 0.27 )	0.85 ( 0.25 )
Week 12	0.86 ( 0.32 )	1.41 ( 0.3 )
Week 24	1.07 ( 0.32 )	1.64 ( 0.3 )
Week 36	1.09 ( 0.32 )	1.79 ( 0.3 )
Week 52	1.17 ( 0.31 )	1.88 ( 0.29 )

Statistical analysis at Week 6.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0467

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-1.32

upper limit

-0.06

Statistical analysis at Week 12.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1599

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-1.33

upper limit

0.22

Statistical analysis at Week 24.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1417

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-1.35

upper limit

0.19

Statistical analysis at Week 36.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0724

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

0.06

Statistical analysis at Week 52.

Comparison groups

Phase C - Brexpiprazole (Double-Blind Maintenance Phase) v Phase C - Placebo (Double-Blind Maintenance Phase)

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0608

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

0.03

Adverse events

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Timeframe for reporting adverse events

Adverse events reported from the signing of the informed consent throughout the stabilization and treatment period followed by a follow-up phone call or clinic visit (study physician's discretion) of 30 (+2) days after last dose of study medication.

Adverse event reporting additional description

AEs were collected for participants who received brexpiprazole in the stabilization phase and for participants were randomized to double-blind treatment (brexpiprazole or placebo) and received at least one dose of double-blind study medication in Double-Blind Maintenance Phase.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Single Blind Stabilization Phase

Reporting group description

Reporting group title

Brexpiprazole (Double-blind Maintenance Phase)

Reporting group description

Participants received maintenance treatment daily with brexpiprazole (at the final dose achieved during the stabilization phase) for up to 52 weeks.

Reporting group title

Placebo (Double-blnd Maintenance Phase)

Reporting group description

Participants received placebo orally once daily for 52 weeks.

Serious adverse events	Single Blind Stabilization Phase	Brexpiprazole (Double-blind Maintenance Phase)	Placebo (Double-blnd Maintenance Phase)
Total subjects affected by serious adverse events
subjects affected / exposed	34 / 464 (7.33%)	3 / 97 (3.09%)	11 / 104 (10.58%)
number of deaths (all causes)	1	0	0
number of deaths resulting from adverse events	0	0	0
Investigations
Hepatic enzyme increased
subjects affected / exposed	0 / 464 (0.00%)	1 / 97 (1.03%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Burns second degree
subjects affected / exposed	1 / 464 (0.22%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gun shot wound
subjects affected / exposed	1 / 464 (0.22%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	1 / 464 (0.22%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	1 / 464 (0.22%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 464 (0.00%)	0 / 97 (0.00%)	1 / 104 (0.96%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina unstable
subjects affected / exposed	0 / 464 (0.00%)	0 / 97 (0.00%)	1 / 104 (0.96%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	0 / 464 (0.00%)	0 / 97 (0.00%)	1 / 104 (0.96%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Convulsion
subjects affected / exposed	1 / 464 (0.22%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	1 / 464 (0.22%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Major depression
subjects affected / exposed	1 / 464 (0.22%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	3 / 464 (0.65%)	1 / 97 (1.03%)	4 / 104 (3.85%)
occurrences causally related to treatment / all	1 / 3	1 / 1	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Schizophrenia
subjects affected / exposed	22 / 464 (4.74%)	1 / 97 (1.03%)	5 / 104 (4.81%)
occurrences causally related to treatment / all	3 / 23	0 / 1	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Schizophrenia, paranoid type
subjects affected / exposed	1 / 464 (0.22%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	3 / 464 (0.65%)	0 / 97 (0.00%)	1 / 104 (0.96%)
occurrences causally related to treatment / all	0 / 3	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 464 (0.22%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
subjects affected / exposed	1 / 464 (0.22%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Single Blind Stabilization Phase	Brexpiprazole (Double-blind Maintenance Phase)	Placebo (Double-blnd Maintenance Phase)
Total subjects affected by non serious adverse events
subjects affected / exposed	148 / 464 (31.90%)	0 / 97 (0.00%)	0 / 104 (0.00%)
Investigations
Weight increased
subjects affected / exposed	24 / 464 (5.17%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences all number	27	1	0
Nervous system disorders
Akathisia
subjects affected / exposed	42 / 464 (9.05%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences all number	57	1	1
Headache
subjects affected / exposed	23 / 464 (4.96%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences all number	42	6	12
Psychiatric disorders
Insomnia
subjects affected / exposed	56 / 464 (12.07%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences all number	90	9	8
Schizophrenia
subjects affected / exposed	28 / 464 (6.03%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences all number	7	2	2
Agitation
subjects affected / exposed	30 / 464 (6.47%)	0 / 97 (0.00%)	0 / 104 (0.00%)
occurrences all number	42	1	6

More information

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

As the interim analysis results were positive, the trial was completed as it achieved the primary endpoint of a significant delay in time to impending relapse for participants randomized to brexpiprazole when compared to participants in placebo.

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Clinical trials

Clinical Trial Results: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults with Schizophrenia.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.

Primary: Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.

Secondary: Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance Phase

Secondary: Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance Phase

Secondary: Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis

Secondary: Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis

Other pre-specified: Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase

Other pre-specified: Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase

Other pre-specified: Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis

Other pre-specified: Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis

Other pre-specified: Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis

Other pre-specified: Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis

Other pre-specified: Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis

Other pre-specified: Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis

Other pre-specified: Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis

Other pre-specified: Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis

Other pre-specified: Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis

Other pre-specified: Mean Change From Baseline in Personal and Social Performance (PSP) Scale Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in Personal and Social Performance (PSP) Scale Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PSP Scale Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PSP Scale Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in GAF Scale Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in GAF Scale Score - LOCF Analysis

Other pre-specified: Percentage of Participants Who Discontinued Due to All Causes

Other pre-specified: Percentage of Participants Who Discontinued Due to All Causes

Other pre-specified: Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PEC Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PEC Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis

Other pre-specified: Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults with Schizophrenia.