Borderline Personality Disorder
Conditions
Brief summary
There are currently no pharmacological treatments approved to treat borderline personality disorder (BPD). This trial will be conducted to evaluate the efficacy and safety of brexpiprazole for the treatment of participants diagnosed with BPD to provide a pharmacological treatment for BPD.
Interventions
DRUGBrexpiprazole
Tablet
OTHERPlacebo
Tablet
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants, ages 18 to 65, inclusive, at the time of informed consent * Participants with a primary Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnosis of BPD confirmed by the Structured Clinical Interview for DSM-5 Personality Disorders (SCID-5-PD) at screening. * At screening and Day 0, participants must have a total score ≥ 12 on the Zanarini Rating Scale for BPD (ZAN-BPD) scale. * Participants who, in the investigator's judgment, require treatment with a medication for BPD. * Participants willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period.
Exclusion criteria
* Sexually active males or females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of investigational medicinal product (IMP). Consensual sexual activity that cannot biologically result in pregnancy may not be participant to required birth control methods, following discussion with the medical monitor. Male participants must also agree not to donate sperm from trial screening through 30 days after the last dose of IMP. * Women who are breastfeeding and/or who have a positive pregnancy test result prior to receiving IMP. * Participants with a concurrent DSM-5 diagnosis of schizophrenia or schizoaffective disorder. Also, participants with a concurrent diagnosis of bipolar I disorder, bipolar II disorder, delirium, dementia, amnesia, eating disorder, antisocial personality disorder, or other cognitive disorders. * Participants with a current diagnosis of substance or alcohol use disorder within 90 days prior to screening visit. * Participants who fulfill the following criteria related to suicide and/or suicidal ideation are excluded: * Participants who have a significant risk of committing violent acts, serious self-harm, or suicide based on history or routine psychiatric status examination, or those who are homicidal or considered to be a high risk to others, or participants with a response of yes on the Columbia-suicide severity rating scale (C-SSRS) Suicidal Ideation Item 5, OR * Participants with a response of yes on the C-SSRS Suicidal Behavior Items, OR * Participants who have had 3 suicide attempts, OR, * Participants who have had 3 or more hospitalizations due to suicidal behavior. * Participants who received brexpiprazole in any prior clinical trial or participants who have taken or are taking commercially available brexpiprazole (Rexulti®). * Participants who are currently either inpatient or partially hospitalized. * Participants who participated in a clinical trial within 90 days prior to screening or who participated in more than 2 clinical trials within a year prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Total Score | Baseline (Day 0) to Week 10 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Patient's Global Impression of Severity (PGI-S) | 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. |
| Patient's Global Impression of Change (PGI-C) Scale Score | 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. |
| Clinical Global Impression - Improvement (CGI-I) Scale Score | Weeks 2, 4, 6, 8, 10 and 12 | 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From Baseline (Day 0) to 21 days after last dose (Up to Week 15) | 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. |
| Number of Participants With Potentially Clinically Relevant Laboratory Test Values | From first dose of study drug up to Week 12 | 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. |
| Number of Participants With Potential Clinical Relevant Laboratory Test Values - Prolactin | 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. |
| Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | 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. |
| Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Baseline (Day 0) to Week 10 | 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. |
| Change From Baseline in Waist Circumference | Baseline (Screening: Day -21 to Day -1), Week 12 | — |
| Change From Baseline in Body Mass Index (BMI) | Baseline (Day 0), Weeks 2, 4, 6, 8, 10, and 12 | BMI is defined as weight in kilograms divided by the square of height in meters. |
| Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters | Week 12 | 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. |
| Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Baseline (Day 0), Week 6 and 12 | 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. |
| Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Baseline (Day 0), Weeks 6 and 12 | 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. |
| Change From Baseline in Barnes Akathisia Rating Scale (BARS): Global Clinical Assessment of Akathisia Score | Baseline (Day 0), Weeks 6 and 12 | 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. |
| Number of Participants With Suicidal Behavior and Suicidal Ideation As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline (Day 0) to Week 12 | 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. |
| Change From Baseline in Body Weight | Baseline (Day 0), Weeks 2, 4, 6, 8, 10, and 12 | — |
Countries
Spain, Ukraine, United States
Participant flow
Recruitment details
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.
Pre-assignment details
332 participants were enrolled out of which 324 participants were randomized to receive brexpiprazole or matching placebo in the treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole 2 to 3 Milligrams Per Day Participants received brexpiprazole, 2-3 mg/day tablets, orally, up to Week 12 during the treatment phase. | 159 |
| Placebo Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase. | 165 |
| Total | 324 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 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
| Characteristic | Placebo | Total | Brexpiprazole 2 to 3 Milligrams Per Day |
|---|---|---|---|
| Age, Continuous | 31.0 years STANDARD_DEVIATION 10.9 | 31.5 years STANDARD_DEVIATION 10.7 | 32.0 years STANDARD_DEVIATION 10.6 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 33 Participants | 64 Participants | 31 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 131 Participants | 258 Participants | 127 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 41 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 15 Participants | 6 Participants |
| Race (NIH/OMB) White | 131 Participants | 254 Participants | 123 Participants |
| Sex: Female, Male Female | 137 Participants | 266 Participants | 129 Participants |
| Sex: Female, Male Male | 28 Participants | 58 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 157 | 0 / 165 |
| other Total, other adverse events | 69 / 157 | 45 / 165 |
| serious Total, serious adverse events | 5 / 157 | 2 / 165 |
Outcome results
Primary
Change From Baseline in the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Total Score
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Total Score | -7.27 score on a scale | Standard Error 0.8 |
| Placebo | Change From Baseline in the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Total Score | -6.25 score on a scale | Standard Error 0.76 |
p-value: 0.24395% CI: [-2.75, 0.7]MMRM
Secondary
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Baseline (Day 0) | 0.03 score on a scale | Standard Deviation 0.2 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Placebo | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Baseline (Day 0) | 0.04 score on a scale | Standard Deviation 0.42 |
| Placebo | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 6 | 0.09 score on a scale | Standard Deviation 0.87 |
| Placebo | Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 12 | 0.07 score on a scale | Standard Deviation 0.73 |
Comparison: Week 6p-value: 0.097495% CI: [-0.25, 0.02]ANCOVA
Comparison: Week 12p-value: 0.39195% CI: [-0.2, 0.08]ANCOVA
Secondary
Change From Baseline in Barnes Akathisia Rating Scale (BARS): Global Clinical Assessment of Akathisia Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Placebo | Change From Baseline in Barnes Akathisia Rating Scale (BARS): Global Clinical Assessment of Akathisia Score | Baseline (Day 0) | 0.12 score on a scale | Standard Deviation 0.4 |
| Placebo | Change From Baseline in Barnes Akathisia Rating Scale (BARS): Global Clinical Assessment of Akathisia Score | Change from Baseline at Week 6 | -0.04 score on a scale | Standard Deviation 0.37 |
| Placebo | Change From Baseline in Barnes Akathisia Rating Scale (BARS): Global Clinical Assessment of Akathisia Score | Change from Baseline at Week 12 | -0.05 score on a scale | Standard Deviation 0.33 |
Comparison: Week 6p-value: 0.00639% CI: [0.04, 0.26]ANCOVA
Comparison: Week 12p-value: 0.06795% CI: [-0.01, 0.19]ANCOVA
Secondary
Change From Baseline in Body Mass Index (BMI)
BMI is defined as weight in kilograms divided by the square of height in meters.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 1.1 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Body Mass Index (BMI) | Baseline (Day 0) | 27.35 kilograms per square meter (kg/m^2) | Standard Deviation 7.49 |
| Placebo | Change From Baseline in Body Mass Index (BMI) | Change From Baseline at Week 12 | 0.13 kilograms per square meter (kg/m^2) | Standard Deviation 1.01 |
| Placebo | Change From Baseline in Body Mass Index (BMI) | Baseline (Day 0) | 28.52 kilograms per square meter (kg/m^2) | Standard Deviation 7.69 |
| Placebo | Change From Baseline in Body Mass Index (BMI) | Change From Baseline at Week 2 | 0.05 kilograms per square meter (kg/m^2) | Standard Deviation 0.62 |
| Placebo | Change From Baseline in Body Mass Index (BMI) | Change From Baseline at Week 4 | -0.00 kilograms per square meter (kg/m^2) | Standard Deviation 0.75 |
| Placebo | Change From Baseline in Body Mass Index (BMI) | Change From Baseline at Week 6 | 0.09 kilograms per square meter (kg/m^2) | Standard Deviation 0.83 |
| Placebo | Change From Baseline in Body Mass Index (BMI) | Change From Baseline at Week 8 | 0.00 kilograms per square meter (kg/m^2) | Standard Deviation 0.89 |
| Placebo | Change From Baseline in Body Mass Index (BMI) | Change From Baseline at Week 10 | 0.15 kilograms per square meter (kg/m^2) | Standard Deviation 1 |
Comparison: Week 2p-value: 0.461395% CI: [-0.08, 0.17]ANCOVA
Comparison: Week 4p-value: 095% CI: [0.21, 0.55]ANCOVA
Comparison: Week 6p-value: 0.000195% CI: [0.21, 0.61]ANCOVA
Comparison: Week 8p-value: 095% CI: [0.33, 0.8]ANCOVA
Comparison: Week 10p-value: 095% CI: [0.34, 0.88]ANCOVA
Comparison: Week 12p-value: 0.000495% CI: [0.23, 0.8]ANCOVA
Secondary
Change From Baseline in Body Weight
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Body Weight | Change From Baseline at Week 4 | 1.05 kilogram (kg) | Standard Deviation 1.92 |
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Body Weight | Change From Baseline at Week 8 | 1.55 kilogram (kg) | Standard Deviation 2.75 |
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Body Weight | Change From Baseline at Week 2 | 0.27 kilogram (kg) | Standard Deviation 1.15 |
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Body Weight | Change From Baseline at Week 10 | 2.09 kilogram (kg) | Standard Deviation 2.96 |
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Body Weight | Change From Baseline at Week 6 | 1.39 kilogram (kg) | Standard Deviation 2.25 |
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Body Weight | Change From Baseline at Week 12 | 1.74 kilogram (kg) | Standard Deviation 3.09 |
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Body Weight | Baseline (Day 0) | 78.60 kilogram (kg) | Standard Deviation 22.15 |
| Placebo | Change From Baseline in Body Weight | Change From Baseline at Week 12 | 0.30 kilogram (kg) | Standard Deviation 2.75 |
| Placebo | Change From Baseline in Body Weight | Baseline (Day 0) | 78.85 kilogram (kg) | Standard Deviation 22.33 |
| Placebo | Change From Baseline in Body Weight | Change From Baseline at Week 2 | 0.09 kilogram (kg) | Standard Deviation 1.62 |
| Placebo | Change From Baseline in Body Weight | Change From Baseline at Week 4 | -0.05 kilogram (kg) | Standard Deviation 2.02 |
| Placebo | Change From Baseline in Body Weight | Change From Baseline at Week 6 | 0.20 kilogram (kg) | Standard Deviation 2.21 |
| Placebo | Change From Baseline in Body Weight | Change From Baseline at Week 8 | -0.03 kilogram (kg) | Standard Deviation 2.41 |
| Placebo | Change From Baseline in Body Weight | Change From Baseline at Week 10 | 0.37 kilogram (kg) | Standard Deviation 2.72 |
Comparison: Week 2p-value: 0.27295% CI: [-0.14, 0.5]ANCOVA
Comparison: Week 4p-value: 095% CI: [0.63, 1.56]ANCOVA
Comparison: Week 6p-value: 095% CI: [0.63, 1.73]ANCOVA
Comparison: Week 8p-value: 095% CI: [0.92, 2.21]ANCOVA
Comparison: Week 10p-value: 095% CI: [0.99, 2.45]ANCOVA
Comparison: Week 12p-value: 0.000295% CI: [0.68, 2.19]ANCOVA
Secondary
Change From Baseline in Simpson-Angus Scale (SAS) Total Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Baseline (Day 0) | 0.18 score on a scale | Standard Deviation 0.65 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Placebo | Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Baseline (Day 0) | 0.24 score on a scale | Standard Deviation 0.92 |
| Placebo | Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 6 | -0.08 score on a scale | Standard Deviation 0.55 |
| Placebo | Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 12 | -0.05 score on a scale | Standard Deviation 0.63 |
Comparison: Week 6p-value: 0.168795% CI: [-0.04, 0.25]ANCOVA
Comparison: Week 12p-value: 0.187495% CI: [-0.06, 0.29]ANCOVA
Secondary
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | -1.13 score on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | -1.09 score on a scale | Standard Error 0.14 |
p-value: 0.775995% CI: [-0.35, 0.27]MMRM
Secondary
Change From Baseline in the Patient's Global Impression of Severity (PGI-S)
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.
Time frame: Baseline (Day 0), 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. 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Brexpiprazole 2-3 Milligrams Per Day | 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 |
| Placebo | Change From Baseline in the Patient's Global Impression of Severity (PGI-S) | Change from Baseline at Week 10 | -0.79 score on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in the Patient's Global Impression of Severity (PGI-S) | Change from Baseline at Week 2 | -0.27 score on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline in the Patient's Global Impression of Severity (PGI-S) | Change from Baseline at Week 8 | -0.69 score on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in the Patient's Global Impression of Severity (PGI-S) | Change from Baseline at Week 4 | -0.35 score on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in the Patient's Global Impression of Severity (PGI-S) | Change from Baseline at Week 12 | -0.86 score on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline in the Patient's Global Impression of Severity (PGI-S) | Change from Baseline at Week 6 | -0.72 score on a scale | Standard Error 0.14 |
Comparison: Week 2p-value: 0.658595% CI: [-0.32, 0.2]MMRM
Comparison: Week 4p-value: 0.118195% CI: [-0.57, 0.06]MMRM
Comparison: Week 6p-value: 0.243195% CI: [-0.51, 0.13]MMRM
Comparison: Week 8p-value: 0.063895% CI: [-0.61, 0.02]MMRM
Comparison: Week 10p-value: 0.50595% CI: [-0.44, 0.22]MMRM
Comparison: Week 12p-value: 0.427795% CI: [-0.48, 0.21]MMRM
Secondary
Change From Baseline in Waist Circumference
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Waist Circumference | Baseline (Screening: Day -21 to Day -1) | 89.74 centimeter | Standard Deviation 17.54 |
| Brexpiprazole 2-3 Milligrams Per Day | Change From Baseline in Waist Circumference | Change from Baseline at Week 12 | 1.07 centimeter | Standard Deviation 5.23 |
| Placebo | Change From Baseline in Waist Circumference | Baseline (Screening: Day -21 to Day -1) | 90.01 centimeter | Standard Deviation 17.25 |
| Placebo | Change From Baseline in Waist Circumference | Change from Baseline at Week 12 | -0.32 centimeter | Standard Deviation 5.76 |
Comparison: Week 12p-value: 0.06295% CI: [-0.07, 2.68]ANCOVA
Secondary
Clinical Global Impression - Improvement (CGI-I) Scale Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 2 | 2.99 score on a scale | Standard Deviation 0.96 |
| Brexpiprazole 2-3 Milligrams Per Day | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 4 | 2.89 score on a scale | Standard Deviation 1.04 |
| Brexpiprazole 2-3 Milligrams Per Day | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 6 | 2.62 score on a scale | Standard Deviation 1.05 |
| Brexpiprazole 2-3 Milligrams Per Day | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 8 | 2.39 score on a scale | Standard Deviation 1.06 |
| Brexpiprazole 2-3 Milligrams Per Day | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 10 | 2.45 score on a scale | Standard Deviation 1.18 |
| Brexpiprazole 2-3 Milligrams Per Day | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 12 | 2.37 score on a scale | Standard Deviation 1.19 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 10 | 2.61 score on a scale | Standard Deviation 1.2 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 2 | 2.99 score on a scale | Standard Deviation 0.97 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 8 | 2.79 score on a scale | Standard Deviation 1.26 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 4 | 3.00 score on a scale | Standard Deviation 1.2 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 12 | 2.65 score on a scale | Standard Deviation 1.17 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scale Score | Week 6 | 2.77 score on a scale | Standard Deviation 1.21 |
Comparison: Week 2p-value: 0.657995% CI: [-0.29, 0.19]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: 0.372895% CI: [-0.43, 0.16]Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.168495% CI: [-0.5, 0.09]Cochran-Mantel-Haenszel
Comparison: Week 8p-value: 0.004695% CI: [-0.74, -0.13]Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.208795% CI: [-0.51, 0.11]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: 0.038995% CI: [-0.64, -0.02]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Potential Clinical Relevant Laboratory Test Values - Prolactin
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.
Time frame: 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 analysis for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potential Clinical Relevant Laboratory Test Values - Prolactin | Prolactin: >1 x ULN | 37 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potential Clinical Relevant Laboratory Test Values - Prolactin | Prolactin: >2 x ULN | 1 Participants |
| Placebo | Number of Participants With Potential Clinical Relevant Laboratory Test Values - Prolactin | Prolactin: >1 x ULN | 4 Participants |
| Placebo | Number of Participants With Potential Clinical Relevant Laboratory Test Values - Prolactin | Prolactin: >2 x ULN | 1 Participants |
Secondary
Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters | Rhythm: Supraventricular Premature Beat | 0 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters | Rhythm: Ventricular Premature Beat | 1 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters | Conduction: Right Bundle Branch Block | 1 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters | ST/T Morphology: Symmetrical T-Wave Inversion | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters | ST/T Morphology: Symmetrical T-Wave Inversion | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters | Rhythm: Supraventricular Premature Beat | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters | Conduction: Right Bundle Branch Block | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters | Rhythm: Ventricular Premature Beat | 0 Participants |
Secondary
Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs
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.
Time frame: 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). Overall number of participants analyzed = number of participants with data available for analyses for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Heart Rate Supine, Low | 1 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Systolic Blood Pressure Supine, Low | 1 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Heart Rate Standing, High | 2 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Weight, Increase | 5 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Systolic Blood Pressure Standing, Low | 1 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Weight, Decrease | 25 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Orthostatic Hypotension: Low | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Weight, Decrease | 12 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Orthostatic Hypotension: Low | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Heart Rate Standing, High | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Heart Rate Supine, Low | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Systolic Blood Pressure Standing, Low | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Systolic Blood Pressure Supine, Low | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Abnormalities in Vital Signs | Weight, Increase | 3 Participants |
Secondary
Number of Participants With Potentially Clinically Relevant Laboratory Test Values
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Alkaline Phosphatase, High | 1 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Aspartate Aminotransferase, High | 1 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Bilirubin, High | 0 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Cho, High | 2 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Cho Fasting, High | 13 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Creatine Kinase, High | 4 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Creatinine, High | 1 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Glu Fasting, High | 29 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: HDL Cho, Fasting, Low | 46 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Low LDL Cho, High | 3 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: LDL Cholesterol, Fasting, High | 11 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Prolactin, High | 41 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Triglyceride, Fasting, High | 35 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Urate, High | 1 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Urea Nitrogen, High | 2 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hem: Eosi/Leukocytes Ratio, High | 4 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hem: Hematocrit, Low | 2 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hem: Hemoglobin, Low | 2 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hematology: Leukocytes, Low | 0 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hem: Leukocytes, High | 2 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hem: Platelets, Low | 0 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Uri: Glu, Urine, High | 0 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Uri: Protein, Urine, High | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Prolactin, High | 7 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Alkaline Phosphatase, High | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hem: Hemoglobin, Low | 2 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Aspartate Aminotransferase, High | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Triglyceride, Fasting, High | 25 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Bilirubin, High | 2 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hem: Platelets, Low | 2 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Cho, High | 4 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Urate, High | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Cho Fasting, High | 7 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hematology: Leukocytes, Low | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Creatine Kinase, High | 3 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Urea Nitrogen, High | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Creatinine, High | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Uri: Protein, Urine, High | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Glu Fasting, High | 30 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hem: Eosi/Leukocytes Ratio, High | 2 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: HDL Cho, Fasting, Low | 42 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hem: Leukocytes, High | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: Low LDL Cho, High | 4 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Hem: Hematocrit, Low | 4 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Che: LDL Cholesterol, Fasting, High | 8 Participants |
| Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Test Values | Uri: Glu, Urine, High | 1 Participants |
Secondary
Number of Participants With Suicidal Behavior and Suicidal Ideation As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
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.
Time frame: Baseline (Day 0) to Week 12
Population: Safety population included those participants who received at least 1 dose of study drug (brexpiprazole or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Suicidal Behavior and Suicidal Ideation As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 42 Participants |
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Suicidal Behavior and Suicidal Ideation As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 78 Participants |
| Placebo | Number of Participants With Suicidal Behavior and Suicidal Ideation As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 29 Participants |
| Placebo | Number of Participants With Suicidal Behavior and Suicidal Ideation As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 70 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 95 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 79 Participants |
Secondary
Patient's Global Impression of Change (PGI-C) Scale Score
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.
Time frame: 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. 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2-3 Milligrams Per Day | Patient's Global Impression of Change (PGI-C) Scale Score | Week 8 | 2.94 score on a scale | Standard Deviation 1.1 |
| Brexpiprazole 2-3 Milligrams Per Day | Patient's Global Impression of Change (PGI-C) Scale Score | Week 4 | 3.23 score on a scale | Standard Deviation 1.26 |
| Brexpiprazole 2-3 Milligrams Per Day | Patient's Global Impression of Change (PGI-C) Scale Score | Week 10 | 2.89 score on a scale | Standard Deviation 1.26 |
| Brexpiprazole 2-3 Milligrams Per Day | Patient's Global Impression of Change (PGI-C) Scale Score | Week 6 | 2.94 score on a scale | Standard Deviation 1.14 |
| Brexpiprazole 2-3 Milligrams Per Day | Patient's Global Impression of Change (PGI-C) Scale Score | Week 12 | 2.88 score on a scale | Standard Deviation 1.19 |
| Brexpiprazole 2-3 Milligrams Per Day | Patient's Global Impression of Change (PGI-C) Scale Score | Week 2 | 3.38 score on a scale | Standard Deviation 0.89 |
| Placebo | Patient's Global Impression of Change (PGI-C) Scale Score | Week 12 | 2.96 score on a scale | Standard Deviation 1.14 |
| Placebo | Patient's Global Impression of Change (PGI-C) Scale Score | Week 2 | 3.30 score on a scale | Standard Deviation 0.93 |
| Placebo | Patient's Global Impression of Change (PGI-C) Scale Score | Week 6 | 3.15 score on a scale | Standard Deviation 1.11 |
| Placebo | Patient's Global Impression of Change (PGI-C) Scale Score | Week 8 | 3.11 score on a scale | Standard Deviation 1.12 |
| Placebo | Patient's Global Impression of Change (PGI-C) Scale Score | Week 10 | 2.97 score on a scale | Standard Deviation 1.2 |
| Placebo | Patient's Global Impression of Change (PGI-C) Scale Score | Week 4 | 3.25 score on a scale | Standard Deviation 1.22 |
Comparison: Week 8p-value: 0.192295% CI: [-0.5, 0.1]Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.648895% CI: [-0.4, 0.25]Cochran-Mantel-Haenszel
Comparison: Week 2p-value: 0.622595% CI: [-0.18, 0.3]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: 0.914595% CI: [-0.35, 0.31]Cochran-Mantel-Haenszel
Comparison: Week 6p-value: 0.153595% CI: [-0.52, 0.08]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: 0.599295% CI: [-0.4, 0.23]Cochran-Mantel-Haenszel