A Trial of Brexpiprazole in the Treatment of Borderline Personality Disorder

A Multicenter, Randomized, Flexible-dose, Double-blind Trial of Brexpiprazole Versus Placebo for the Treatment of Adults With Borderline Personality Disorder

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.

Study Overview

• Status: Completed
• Conditions: Borderline Personality Disorder
• Intervention / Treatment: Drug: Brexpiprazole; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 332
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Institut Hospital del Mar d'Investigacions Mèdiques - IMIM
  • Barcelona, Spain, 08025
    • Consultoria i Projectes Sanitaris S.L. Clinic: Hestia Palau
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau Carrer de Sant Quint
  • Madrid, Spain, 28031
    • Hospital Universitario Infanta Leonor
  • Zamora, Spain, 49021
    • Hospital Provincial de Zamora
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Hospital Parc Taul Parc Tauli 1
• Ukraine
  • Kharkiv, Ukraine, 61068
    • Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine
  • Kyiv, Ukraine, 1030
    • Kyiv railway clinical hospital 1
  • Odessa, Ukraine, 65006
    • Odessa Regional Medical Centre of Mental Health
  • Poltava, Ukraine, 36013
    • Communal Enterprise-Regional Institution of Mental Psychiatric Care of the Poltava Regional Council
  • Vinnytsia, Ukraine, 21005
    • Vinnitsa National Medical University
• United States
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Pillar Clinical Research
  • California
    • Bellflower, California, United States, 90706
      • CI Trials
    • Beverly Hills, California, United States, 90212
      • Care Access Research Beverly Hills
    • Lancaster, California, United States, 93534
      • Om Research LLC
    • Los Angeles, California, United States, 90024
      • CalNeuro Research Group
    • Oceanside, California, United States, 92056
      • Excell Research
    • San Diego, California, United States, 92108
      • PCSD - Feighner Research
    • San Rafael, California, United States, 94901
      • SF-Care Inc.
    • Santa Ana, California, United States, 92705
      • CI Trials
    • Temecula, California, United States, 90706
      • Viking Clinical Research
    • Upland, California, United States, 91786
      • Pacific Clinical Research Management Group
  • Colorado
    • Denver, Colorado, United States, 80209
      • Mountain View Clinical Research, Inc.
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut
    • Hartford, Connecticut, United States, 06106
      • Institute of Living Hartford Hospital
    • Norwich, Connecticut, United States, 06360
      • Comprehensive Psychiatric Care
  • Florida
    • Boca Raton, Florida, United States, 33431
      • Mindful Behavioral Health
    • Coral Springs, Florida, United States, 33067
      • CNS Clinical Research of Coral Springs
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Clinical Research Center
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Hialeah, Florida, United States, 33016
      • Galiz Research
    • Hialeah, Florida, United States, 33012
      • New Life Medical Research Center
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions Inc.
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research, INC
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions dba CNS Healthcare
    • Orlando, Florida, United States, 32803
      • APG Research
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Institute for Advanced Medical Research
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Hospitals
    • Naperville, Illinois, United States, 60563
      • AMR Conventions Research
    • Winfield, Illinois, United States, 60190
      • Neuroscience Research Institute Inc.
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital
    • Boston, Massachusetts, United States, 02116
      • Copley Clinical
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Advanced Clinical Research Center, LLC
    • O'Fallon, Missouri, United States, 63368
      • Psychiatric Care and Research Center
    • Saint Charles, Missouri, United States, 63304
      • St. Charles Psychiatric Associates dba Midwest Research Group
    • Saint Louis, Missouri, United States, 63128
      • PsychCare Consultants Research
    • Saint Louis, Missouri, United States, 63118
      • Arch Clinical Trials LLC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute, LLC
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
  • New York
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials
    • Brooklyn, New York, United States, 11235
      • SPRI Clinical Trials LLC
    • Mount Kisco, New York, United States, 10549
      • Bioscience Research, LLC
    • New York, New York, United States, 10128
      • The Medical Research Network, LLC
    • New York, New York, United States, 10036
      • Manhattan Behavioral Medicine PLLC
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research
    • Raleigh, North Carolina, United States, 27606
      • Mindpath Care Centers
  • Ohio
    • Avon Lake, Ohio, United States, 44012
      • Quest Therapeutics of Avon Lake
    • Mason, Ohio, United States, 45040
      • Lindner Center of Hope
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Sooner Clinical Research
    • Oklahoma City, Oklahoma, United States, 73118
      • Paradigm Research Professionals
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Carolina Clinical Trials Inc.
  • Texas
    • Dallas, Texas, United States, 75243
      • Relaro Medical Trials, LLC
    • Houston, Texas, United States, 77058
      • Earle Research
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatric Associates
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Research
    • San Antonio, Texas, United States, 78229
      • The University of Texas Heath Science Center at San Antonio
    • Wichita Falls, Texas, United States, 76309
      • Grayline Research Center
  • Utah
    • Salt Lake City, Utah, United States, 84105
      • Psychiatric Behavioral Solutions
    • Springville, Utah, United States, 84663
      • Cedar Psychiatry
  • Vermont
    • Woodstock, Vermont, United States, 05091
      • Woodstock Research Center
  • Washington
    • Everett, Washington, United States, 98201
      • Eastside Therapeutic Resource Inc dba Core Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brexpiprazole 2-3 Milligrams Per Day; Participants received brexpiprazole, 2-3 milligrams per day (mg/day) tablets, orally, up to Week 12 during the treatment phase.	Drug: Brexpiprazole; Tablet; Other Names: Rexulti®
Placebo Comparator: Placebo; Participants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.	Other: Placebo; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 0) to Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 0) to Week 10
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.	Baseline (Day 0), Weeks 2, 4, 6, 8, 10 and 12
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.	Weeks 2, 4, 6, 8,10 and 12
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.	Weeks 2, 4, 6, 8, 10 and 12
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.	From Baseline (Day 0) to 21 days after last dose (Up to Week 15)
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.	From first dose of study drug up to Week 12
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.	Week 12
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.	From first dose of study drug up to Week 12
Change From Baseline in Body Weight		Baseline (Day 0), Weeks 2, 4, 6, 8, 10, and 12
Change From Baseline in Waist Circumference		Baseline (Screening: Day -21 to Day -1), Week 12
Change From Baseline in Body Mass Index (BMI)	BMI is defined as weight in kilograms divided by the square of height in meters.	Baseline (Day 0), Weeks 2, 4, 6, 8, 10, and 12
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.	Week 12
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.	Baseline (Day 0), Week 6 and 12
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.	Baseline (Day 0), Weeks 6 and 12
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.	Baseline (Day 0), Weeks 6 and 12
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.	Baseline (Day 0) to Week 12

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

General Publications

• Stoffers-Winterling JM, Storebo OJ, Pereira Ribeiro J, Kongerslev MT, Vollm BA, Mattivi JT, Faltinsen E, Todorovac A, Jorgensen MS, Callesen HE, Sales CP, Schaug JP, Simonsen E, Lieb K. Pharmacological interventions for people with borderline personality disorder. Cochrane Database Syst Rev. 2022 Nov 14;11(11):CD012956. doi: 10.1002/14651858.CD012956.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Actual): June 27, 2021
• Study Completion (Actual): June 27, 2021

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: September 20, 2019
• First Posted (Actual): September 24, 2019

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: June 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Borderline Personality Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Dopamine Agonists; Dopamine Agents; Brexpiprazole
• Other Study ID Numbers: 331-201-00242

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No