Trial Outcomes & Findings for A Trial of Brexpiprazole in the Treatment of Borderline Personality Disorder (NCT NCT04100096)

Last Updated: 2024-07-18

Results Overview

The ZAN-BPD is a clinician-administered scale designed to assess severity of disease symptoms in participants with BPD based on clinician rating on 9 criteria. Each of the 9 criteria for BPD was rated on a 5-point anchored rating scale of 0 to 4. These scores were clustered into 4 sector scores (akin to domains) and a total score. The 4 sector scores added up to provide the overall total score for the ZAN-BPD, which ranged from 0 to 36. A higher score represented a higher severity of disease symptoms. Mixed model repeated measures = MMRM, antidepressant therapy = ADT.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

332 participants

Primary outcome timeframe

Baseline (Day 0) to Week 10

Results posted on

2024-07-18

Participant Flow

Participants were enrolled in the study at 62 study centers in the United States, Spain, and Ukraine from 17 October 2019 to 27 Jun 2021.

332 participants were enrolled out of which 324 participants were randomized to receive brexpiprazole or matching placebo in the treatment phase.

Participant milestones

Participant milestones
Measure	Brexpiprazole 2-3 Milligrams Per Day Participants received brexpiprazole, 2-3 milligrams per day (mg/day) tablets, orally, up to Week 12 during treatment phase.	Placebo Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during treatment phase.
Overall Study STARTED	159	165
Overall Study Safety Population	157	165
Overall Study Full Analysis Set (FAS) for Enriched Participants	112	111
Overall Study COMPLETED	112	127
Overall Study NOT COMPLETED	47	38

Reasons for withdrawal

Reasons for withdrawal
Measure	Brexpiprazole 2-3 Milligrams Per Day Participants received brexpiprazole, 2-3 milligrams per day (mg/day) tablets, orally, up to Week 12 during treatment phase.	Placebo Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during treatment phase.
Overall Study Adverse Event	19	7
Overall Study Lack of Efficacy	0	1
Overall Study Lost to Follow-up	13	11
Overall Study Non-Compliance With Study Drug	1	3
Overall Study Protocol Deviation	1	1
Overall Study Withdrawal by Participant	13	15

Baseline Characteristics

A Trial of Brexpiprazole in the Treatment of Borderline Personality Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brexpiprazole 2 to 3 Milligrams Per Day n=159 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=165 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.	Total n=324 Participants Total of all reporting groups
Age, Continuous	32.0 years STANDARD_DEVIATION 10.6 • n=5 Participants	31.0 years STANDARD_DEVIATION 10.9 • n=7 Participants	31.5 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	129 Participants n=5 Participants	137 Participants n=7 Participants	266 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	28 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	19 Participants n=5 Participants	22 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) White	123 Participants n=5 Participants	131 Participants n=7 Participants	254 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	31 Participants n=5 Participants	33 Participants n=7 Participants	64 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	127 Participants n=5 Participants	131 Participants n=7 Participants	258 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0) to Week 10

Population: FAS for enriched participants is a subset of randomized population who met pre-defined criteria and who received at least 1 dose of double-blind investigational medicinal product (IMP) and had a baseline value and at least 1 valid post-randomization efficacy evaluation for ZAN-BPD total score. Overall number of participants analyzed = number of participants with data available for analysis for this outcome measure.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=86 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=91 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Change From Baseline in the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Total Score	-7.27 score on a scale Standard Error 0.80	-6.25 score on a scale Standard Error 0.76

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 10

Population: FAS for enriched participants is a subset of randomized population who met pre-defined criteria and who received at least 1 valid post-randomization efficacy evaluation for ZAN-BPD total score. Overall number of participants analyzed = number of participants with data available for analysis for this outcome measure.

The severity of illness for each participant was rated using the CGI-S. CGI-S is an observer-rated scale with a total score range of 0 to 7 where a higher score represented a worse outcome. The response choices were 0 = not assessed; 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=86 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=91 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score	-1.13 score on a scale Standard Error 0.14	-1.09 score on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline (Day 0), Weeks 2, 4, 6, 8, 10 and 12

PGI-S is a 7-point single-item self-report scale for the participant to rate the severity of symptoms of BPD ranging from 0 to 7 where 1 denoted no symptoms and 7 denoted very severe.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=107 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=107 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Change From Baseline in the Patient's Global Impression of Severity (PGI-S) Change from Baseline at Week 2	-0.33 score on a scale Standard Error 0.12	-0.27 score on a scale Standard Error 0.12
Change From Baseline in the Patient's Global Impression of Severity (PGI-S) Change from Baseline at Week 4	-0.60 score on a scale Standard Error 0.15	-0.35 score on a scale Standard Error 0.14
Change From Baseline in the Patient's Global Impression of Severity (PGI-S) Change from Baseline at Week 6	-0.91 score on a scale Standard Error 0.15	-0.72 score on a scale Standard Error 0.14
Change From Baseline in the Patient's Global Impression of Severity (PGI-S) Change from Baseline at Week 8	-0.99 score on a scale Standard Error 0.14	-0.69 score on a scale Standard Error 0.14
Change From Baseline in the Patient's Global Impression of Severity (PGI-S) Change from Baseline at Week 10	-0.90 score on a scale Standard Error 0.15	-0.79 score on a scale Standard Error 0.14
Change From Baseline in the Patient's Global Impression of Severity (PGI-S) Change from Baseline at Week 12	-1.00 score on a scale Standard Error 0.16	-0.86 score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Weeks 2, 4, 6, 8,10 and 12

A 7-point single-item self-report scale depicting a participant's rating of overall change in their condition since starting trial medication. Participants answered the question: "Since starting study medication, how much have their symptoms of Borderline Personality Disorder changed?" with a score ranging from 1 to 7 where 1 denoted very much improved and 7 denoted very much worse.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=109 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=110 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Patient's Global Impression of Change (PGI-C) Scale Score Week 12	2.88 score on a scale Standard Deviation 1.19	2.96 score on a scale Standard Deviation 1.14
Patient's Global Impression of Change (PGI-C) Scale Score Week 2	3.38 score on a scale Standard Deviation 0.89	3.30 score on a scale Standard Deviation 0.93
Patient's Global Impression of Change (PGI-C) Scale Score Week 4	3.23 score on a scale Standard Deviation 1.26	3.25 score on a scale Standard Deviation 1.22
Patient's Global Impression of Change (PGI-C) Scale Score Week 6	2.94 score on a scale Standard Deviation 1.14	3.15 score on a scale Standard Deviation 1.11
Patient's Global Impression of Change (PGI-C) Scale Score Week 8	2.94 score on a scale Standard Deviation 1.10	3.11 score on a scale Standard Deviation 1.12
Patient's Global Impression of Change (PGI-C) Scale Score Week 10	2.89 score on a scale Standard Deviation 1.26	2.97 score on a scale Standard Deviation 1.20

SECONDARY outcome

Timeframe: Weeks 2, 4, 6, 8, 10 and 12

Population: FAS for enriched participants is a subset of randomized population who met pre-defined criteria and who received at least 1 valid post-randomization efficacy evaluation for ZAN-BPD total score. Number analyzed = number of participants with data available for analyses at the specified time point.

Participant's condition was assessed using CGI-I scale. CGI-I is an observer-rated scale with a total score of 0 to 7 and a higher score represents a worse outcome. The score included the following response choices: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=110 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=110 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Clinical Global Impression - Improvement (CGI-I) Scale Score Week 2	2.99 score on a scale Standard Deviation 0.96	2.99 score on a scale Standard Deviation 0.97
Clinical Global Impression - Improvement (CGI-I) Scale Score Week 4	2.89 score on a scale Standard Deviation 1.04	3.00 score on a scale Standard Deviation 1.20
Clinical Global Impression - Improvement (CGI-I) Scale Score Week 6	2.62 score on a scale Standard Deviation 1.05	2.77 score on a scale Standard Deviation 1.21
Clinical Global Impression - Improvement (CGI-I) Scale Score Week 8	2.39 score on a scale Standard Deviation 1.06	2.79 score on a scale Standard Deviation 1.26
Clinical Global Impression - Improvement (CGI-I) Scale Score Week 10	2.45 score on a scale Standard Deviation 1.18	2.61 score on a scale Standard Deviation 1.20
Clinical Global Impression - Improvement (CGI-I) Scale Score Week 12	2.37 score on a scale Standard Deviation 1.19	2.65 score on a scale Standard Deviation 1.17

SECONDARY outcome

Timeframe: From Baseline (Day 0) to 21 days after last dose (Up to Week 15)

Population: Safety population (SP) included those participants who received at least 1 dose of study drug (brexpiprazole or placebo).

An adverse event (AE) is any untoward medical occurrence in a clinical trial participant administered an IMP and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is defined as an AE that started after start of study treatment.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=157 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=165 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	95 Participants	79 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to Week 12

Population: SP: Participants who received at least 1 dose of study drug (brexpiprazole or placebo). Only those categories with at least one participant with event are reported. Overall number of participants analyzed = number of participants with data available for analysis for this outcome measure. Number analyzed = total number of participants with at least one post-baseline numeric result for given laboratory parameter.

Laboratory parameters included hematology(Hem), serum chemistry(Che) and urinalysis(Uri). Criterion:Che-Alkaline Phosphatase (Units/liter \[U/L\]):≥3 x ULN, Aspartate Aminotransferase (U/L):≥3 x ULN,Bilirubin (mg/deciliter\[dL\]):≥2.0,Cholesterol(Cho);Cho,fasting(mg/dl):≥240,Creatine Kinase(U/L):≥3 x ULN, Creatinine(mg/dL):≥2.0,Glucose (Glu);Glu,fasting(mg/dL):100,High Density Lipoprotein (HDL) Cho (mg/dL):Male (M) \< 40or Female (F) \<50, Low Density Lipoprotein (LDL) Cho(mg/dL):≥160,Prolactin (nanograms/milliliter \[ng/mL\]):\>1 x ULN,Triglyceride (mg/dL):≥150,Urate(mg/dL): M ≥10.5 or F ≥8.5,Urea Nitrogen (mg/dL):≥30,Hem-Eosinophils (Eosi) (10\^9 L):≥10%,Hematocrit (%): M ≤37% and ≥3 percentage (per) point decrease from baseline or F≤32% and ≥3per point decrease from baseline, Hemaglobin(gram per deciliter \[g/dL\]):M ≤11.5 or F ≤9.5,Leukocytes(10\^9/L):≤2.8 x10\^3/uL,≤16.0 x10\^3/uL,Platelets(10\^9/L):≤75 x10\^3/ uL,≥700 x10\^3/uL,Uri-Glu,urine; Protein,urine:Increase of ≥2U.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=146 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=157 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Creatinine, High	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Glu Fasting, High	29 Participants	30 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: HDL Cho, Fasting, Low	46 Participants	42 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: LDL Cholesterol, Fasting, High	11 Participants	8 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Triglyceride, Fasting, High	35 Participants	25 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Urate, High	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Urea Nitrogen, High	2 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Hem: Eosi/Leukocytes Ratio, High	4 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Hem: Hematocrit, Low	2 Participants	4 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Hem: Leukocytes, High	2 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Hem: Platelets, Low	0 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Uri: Glu, Urine, High	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Prolactin, High	41 Participants	7 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Hem: Hemoglobin, Low	2 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Hematology: Leukocytes, Low	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Uri: Protein, Urine, High	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Alkaline Phosphatase, High	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Aspartate Aminotransferase, High	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Bilirubin, High	0 Participants	2 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Cho, High	2 Participants	4 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Cho Fasting, High	13 Participants	7 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Creatine Kinase, High	4 Participants	3 Participants
Number of Participants With Potentially Clinically Relevant Laboratory Test Values Che: Low LDL Cho, High	3 Participants	4 Participants

SECONDARY outcome

Timeframe: Week 12

New onset (\> 1 x upper limit of normal {ULN}, \> 2 x ULN, 3 X ULN) prolactin means a participant who attains a categorical change during treatment phase but not at baseline. Only those categories with at least one participant with event are reported.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=130 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=143 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Number of Participants With Potential Clinical Relevant Laboratory Test Values - Prolactin Prolactin: >1 x ULN	37 Participants	4 Participants
Number of Participants With Potential Clinical Relevant Laboratory Test Values - Prolactin Prolactin: >2 x ULN	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to Week 12

Vital Signs included orthostatic hypotension, heart rate (HR), systolic and diastolic blood pressure (bp), and weight. Potential clinical relevance criterion: Orthostatic Hypotension:\>= 20 millimeters of mercury (mmhg) decrease in systolic bp and \>= 25 beats per minute (bpm) increase in HR from supine to standing; HR Standing (bpm):\< 50 and decrease \>= 15,\> 120 and increase \>= 15; HR Supine (bpm): \< 50 and decrease \>= 15,\>120 and increase \>= 15; Systolic BP Standing (mmhg):\< 90 and decrease \>=20,\> 180 and increase \>= 20; Systolic BP Supine (mmhg):\< 90 and decrease \>= 20, \>180 and increase \>= 20; Diastolic BP Standing (mmHg): \< 50 and decrease \>= 15,\> 105 and increase \>= 15; Diastolic BP Supine (mmHg):\< 50 and decrease \>= 15, \> 105 and increase \>= 15; Weight (kilograms\[kg\]): Decrease or increase \>= 7%. Only those categories with at least one participant with event are reported.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=154 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=165 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Orthostatic Hypotension: Low	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Heart Rate Standing, High	2 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Heart Rate Supine, Low	1 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Systolic Blood Pressure Standing, Low	1 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Systolic Blood Pressure Supine, Low	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Weight, Increase	5 Participants	3 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs Weight, Decrease	25 Participants	12 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0), Weeks 2, 4, 6, 8, 10, and 12

Population: SP: Participants who received at least 1 dose of study drug (brexpiprazole or placebo). Overall number of participants analyzed = number of participants with data available for analyses for this outcome measure. Number analyzed = number of participants with data available for analyses at the specified time point.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=154 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=165 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Change From Baseline in Body Weight Baseline (Day 0)	78.60 kilogram (kg) Standard Deviation 22.15	78.85 kilogram (kg) Standard Deviation 22.33
Change From Baseline in Body Weight Change From Baseline at Week 2	0.27 kilogram (kg) Standard Deviation 1.15	0.09 kilogram (kg) Standard Deviation 1.62
Change From Baseline in Body Weight Change From Baseline at Week 4	1.05 kilogram (kg) Standard Deviation 1.92	-0.05 kilogram (kg) Standard Deviation 2.02
Change From Baseline in Body Weight Change From Baseline at Week 6	1.39 kilogram (kg) Standard Deviation 2.25	0.20 kilogram (kg) Standard Deviation 2.21
Change From Baseline in Body Weight Change From Baseline at Week 8	1.55 kilogram (kg) Standard Deviation 2.75	-0.03 kilogram (kg) Standard Deviation 2.41
Change From Baseline in Body Weight Change From Baseline at Week 10	2.09 kilogram (kg) Standard Deviation 2.96	0.37 kilogram (kg) Standard Deviation 2.72
Change From Baseline in Body Weight Change From Baseline at Week 12	1.74 kilogram (kg) Standard Deviation 3.09	0.30 kilogram (kg) Standard Deviation 2.75

SECONDARY outcome

Timeframe: Baseline (Screening: Day -21 to Day -1), Week 12

Population: SP: Participants who received at least 1 dose of study drug (brexpiprazole or placebo). Overall number of participants analyzed= number of participants with data available for analyses for this outcome measure. Number analyzed= number of participants with data available for analyses at the specified time point.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=134 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=146 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Change From Baseline in Waist Circumference Baseline (Screening: Day -21 to Day -1)	89.74 centimeter Standard Deviation 17.54	90.01 centimeter Standard Deviation 17.25
Change From Baseline in Waist Circumference Change from Baseline at Week 12	1.07 centimeter Standard Deviation 5.23	-0.32 centimeter Standard Deviation 5.76

SECONDARY outcome

Timeframe: Baseline (Day 0), Weeks 2, 4, 6, 8, 10, and 12

Population: SP: Participants who received at least 1 dose of study drug (brexpiprazole or placebo). Overall number of participants analyzed= number of participants with data available for analyses for this outcome measure. Number analyzed= number of participants with data available for analyses at the specified time point.

BMI is defined as weight in kilograms divided by the square of height in meters.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=154 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=165 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Change From Baseline in Body Mass Index (BMI) Change From Baseline at Week 8	0.57 kilograms per square meter (kg/m^2) Standard Deviation 1.01	0.00 kilograms per square meter (kg/m^2) Standard Deviation 0.89
Change From Baseline in Body Mass Index (BMI) Change From Baseline at Week 10	0.76 kilograms per square meter (kg/m^2) Standard Deviation 1.10	0.15 kilograms per square meter (kg/m^2) Standard Deviation 1.00
Change From Baseline in Body Mass Index (BMI) Baseline (Day 0)	27.35 kilograms per square meter (kg/m^2) Standard Deviation 7.49	28.52 kilograms per square meter (kg/m^2) Standard Deviation 7.69
Change From Baseline in Body Mass Index (BMI) Change From Baseline at Week 2	0.09 kilograms per square meter (kg/m^2) Standard Deviation 0.42	0.05 kilograms per square meter (kg/m^2) Standard Deviation 0.62
Change From Baseline in Body Mass Index (BMI) Change From Baseline at Week 4	0.38 kilograms per square meter (kg/m^2) Standard Deviation 0.68	-0.00 kilograms per square meter (kg/m^2) Standard Deviation 0.75
Change From Baseline in Body Mass Index (BMI) Change From Baseline at Week 6	0.50 kilograms per square meter (kg/m^2) Standard Deviation 0.81	0.09 kilograms per square meter (kg/m^2) Standard Deviation 0.83
Change From Baseline in Body Mass Index (BMI) Change From Baseline at Week 12	0.64 kilograms per square meter (kg/m^2) Standard Deviation 1.17	0.13 kilograms per square meter (kg/m^2) Standard Deviation 1.01

SECONDARY outcome

Timeframe: Week 12

Population: SP: Participants who received at least 1 dose of study drug (brexpiprazole or placebo). Overall number of participants analyzed= number of participants with data available for analyses for this outcome measure. Number analyzed = total number of participants with at least one post-baseline numeric result for the given ECG parameter.

ECG parameters analyzed included rhythm, conduction and ST/T morphology. Potential clinical relevance criterion: Rhythm- Supraventricular Premature Beat: not present at baseline and present post baseline, Ventricular Premature Beat: not present at baseline and present post baseline, Conduction- Right Bundle Branch Block: not present at baseline and present post baseline, ST/T Morphology- Symmetrical (Sym) T-Wave Inversion: not present at baseline and present post baseline. Only those categories with at least one participant with event are reported.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=133 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=143 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters Rhythm: Supraventricular Premature Beat	0 Participants	1 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters Rhythm: Ventricular Premature Beat	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters Conduction: Right Bundle Branch Block	1 Participants	0 Participants
Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters ST/T Morphology: Symmetrical T-Wave Inversion	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0), Week 6 and 12

Population: SP: Participants who received at least 1 dose of study drug (brexpiprazole or placebo). Overall number of participants analyzed = number of participants with data available for analysis for this outcome measure. Number analyzed = number of participants with data available for analyses at the specified time point.

The SAS consisted of a list of 10 symptoms of Parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Each item was rated on a 5-point scale, with a score of zero representing the absence of symptoms and a score of 4 representing a severe condition. The SAS total score was the sum of the scores for all 10 items and ranged from 0 to 40. Higher scores indicated worst outcome.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=138 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=148 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Change From Baseline in Simpson-Angus Scale (SAS) Total Score Baseline (Day 0)	0.18 score on a scale Standard Deviation 0.65	0.24 score on a scale Standard Deviation 0.92
Change From Baseline in Simpson-Angus Scale (SAS) Total Score Change from Baseline at Week 12	0.04 score on a scale Standard Deviation 0.88	-0.05 score on a scale Standard Deviation 0.63
Change From Baseline in Simpson-Angus Scale (SAS) Total Score Change from Baseline at Week 6	0.04 score on a scale Standard Deviation 0.76	-0.08 score on a scale Standard Deviation 0.55

SECONDARY outcome

Timeframe: Baseline (Day 0), Weeks 6 and 12

Population: SP: Participants who received at least 1 dose of study drug (brexpiprazole or placebo). Overall number of participants analyzed = number of participants with data available for analysis for this outcome measure. Number analyzed = number of participants with data available for analyses at the specified time point.

AIMS assessment consisted of 10 items describing symptoms of dyskinesia (muscles of facial expression, lips and perioral area, jaw, tongue, upper extremities, lower extremities, neck/shoulders/hips, overall movement severity, incapacitation, participant awareness). Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7) were observed unobtrusively while participant was at rest (e.g., in waiting room), and study physician would make global judgments on participant's dyskinesia's (items 8 through 10). Each item was rated on 5-point scale of severity from 0 (none) to 4 (severe) and assessment of problems with teeth or dentures (yes = 1, no = 0) and if the participant normally wears dentures (yes = 1, no = 0). Total score ranged from 0 to 42. Higher scores indicated worst outcome.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=142 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=148 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score Change from Baseline at Week 12	-0.02 score on a scale Standard Deviation 0.27	0.07 score on a scale Standard Deviation 0.73
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score Baseline (Day 0)	0.03 score on a scale Standard Deviation 0.20	0.04 score on a scale Standard Deviation 0.42
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score Change from Baseline at Week 6	-0.02 score on a scale Standard Deviation 0.25	0.09 score on a scale Standard Deviation 0.87

SECONDARY outcome

Timeframe: Baseline (Day 0), Weeks 6 and 12

Population: Safety population included those participants in who received at least 1 dose of study drug (brexpiprazole or placebo). Overall number of participants analyzed = number of participants with data available for analysis for this outcome measure. Number analyzed = number of participants with data available for analyses at the specified time point.

The BARS consisted of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the participant, subjective distress due to akathisia, and global clinical assessment of akathisia. The global clinical evaluation was made on a 6-point scale, with zero representing absence of symptoms and a score of 5 representing severe akathisia.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=142 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=149 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Change From Baseline in Barnes Akathisia Rating Scale (BARS): Global Clinical Assessment of Akathisia Score Baseline (Day 0)	0.08 score on a scale Standard Deviation 0.27	0.12 score on a scale Standard Deviation 0.40
Change From Baseline in Barnes Akathisia Rating Scale (BARS): Global Clinical Assessment of Akathisia Score Change from Baseline at Week 6	0.15 score on a scale Standard Deviation 0.59	-0.04 score on a scale Standard Deviation 0.37
Change From Baseline in Barnes Akathisia Rating Scale (BARS): Global Clinical Assessment of Akathisia Score Change from Baseline at Week 12	0.06 score on a scale Standard Deviation 0.53	-0.05 score on a scale Standard Deviation 0.33

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 12

Population: Safety population included those participants who received at least 1 dose of study drug (brexpiprazole or placebo).

Suicidality was monitored using the C-SSRS. Suicidality was defined as at least one occurrence of suicidal ideation (including wish to be dead, non-specific suicidal thought, suicidal ideation-no intent, ideation with intent, no plan, ideation with plan/intent) or at least one occurrence of suicidal behavior (actual attempt, non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts/behavior, suicidal behavior) for the assessment period.

Outcome measures

Outcome measures
Measure	Brexpiprazole 2-3 Milligrams Per Day n=157 Participants Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=165 Participants Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Number of Participants With Suicidal Behavior and Suicidal Ideation As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Behavior	42 Participants	29 Participants
Number of Participants With Suicidal Behavior and Suicidal Ideation As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation	78 Participants	70 Participants

Adverse Events

Brexpiprazole 2-3 Milligrams Per Day

Serious events: 5 serious events

Other events: 69 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Brexpiprazole 2-3 Milligrams Per Day n=157 participants at risk Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=165 participants at risk Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Gastrointestinal disorders Gastritis	0.00% 0/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	0.61% 1/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Infections and infestations Pneumonia	0.00% 0/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	0.61% 1/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Nervous system disorders Cerebrovascular Accident	0.64% 1/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	0.00% 0/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Psychiatric disorders Dissociation	0.00% 0/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	0.61% 1/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Psychiatric disorders Major Depression	0.64% 1/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	0.00% 0/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Psychiatric disorders Panic Attack	0.64% 1/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	0.00% 0/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Psychiatric disorders Suicide Attempt	1.3% 2/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	0.00% 0/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).

Other adverse events

Other adverse events
Measure	Brexpiprazole 2-3 Milligrams Per Day n=157 participants at risk Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase.	Placebo n=165 participants at risk Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
General disorders Fatigue	7.6% 12/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	3.6% 6/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Investigations Weight Increased	6.4% 10/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	2.4% 4/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Metabolism and nutrition disorders Increased Appetite	5.1% 8/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	2.4% 4/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Nervous system disorders Akathisia	14.0% 22/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	1.2% 2/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Nervous system disorders Headache	5.1% 8/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	7.3% 12/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Nervous system disorders Somnolence	5.1% 8/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	3.0% 5/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Psychiatric disorders Anxiety	8.3% 13/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	5.5% 9/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Psychiatric disorders Insomnia	9.6% 15/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	6.1% 10/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).
Psychiatric disorders Restlessness	6.4% 10/157 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).	1.2% 2/165 • From Baseline (Day 0) to 21 days after last dose (up to Week 15) Safety population included randomized participants who received at least 1 dose of study drug (brexpiprazole or placebo).

Additional Information

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Results disclosure agreements

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