MedPath

A Trial of Brexpiprazole in the Treatment of Borderline Personality Disorder

Phase 2
Completed
Conditions
Borderline Personality Disorder
Interventions
Other: Placebo
Drug: Brexpiprazole
Registration Number
NCT04100096
Lead Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
332
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.
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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.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants received brexpiprazole-matching placebo tablets, orally, up to Week 12 during the treatment phase.
Brexpiprazole 2-3 Milligrams Per DayBrexpiprazoleParticipants received brexpiprazole, 2-3 milligrams per day (mg/day) tablets, orally, up to Week 12 during the treatment phase.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Total ScoreBaseline (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 Outcome Measures
NameTimeMethod
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) ScoreBaseline (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.

Number of Participants With Potentially Clinically Relevant Laboratory Test ValuesFrom 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.

Change From Baseline in Barnes Akathisia Rating Scale (BARS): Global Clinical Assessment of Akathisia ScoreBaseline (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.

Patient's Global Impression of Change (PGI-C) Scale ScoreWeeks 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.

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.

Change From Baseline in Body WeightBaseline (Day 0), Weeks 2, 4, 6, 8, 10, and 12
Change From Baseline in Waist CircumferenceBaseline (Screening: Day -21 to Day -1), Week 12
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total ScoreBaseline (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.

Number of Participants With Potentially Clinically Relevant Abnormalities in Vital SignsFrom 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.

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 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.

Clinical Global Impression - Improvement (CGI-I) Scale ScoreWeeks 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 Potential Clinical Relevant Laboratory Test Values - ProlactinWeek 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.

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) ParametersWeek 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 ScoreBaseline (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.

Trial Locations

Locations (75)

Institute of Living Hartford Hospital

🇺🇸

Hartford, Connecticut, United States

Mindful Behavioral Health

🇺🇸

Boca Raton, Florida, United States

University of Connecticut

🇺🇸

Farmington, Connecticut, United States

Red Oak Psychiatric Associates

🇺🇸

Houston, Texas, United States

PCSD - Feighner Research

🇺🇸

San Diego, California, United States

Mountain View Clinical Research, Inc.

🇺🇸

Denver, Colorado, United States

Sooner Clinical Research

🇺🇸

Oklahoma City, Oklahoma, United States

The University of Texas Heath Science Center at San Antonio

🇺🇸

San Antonio, Texas, United States

Center for Emotional Fitness

🇺🇸

Cherry Hill, New Jersey, United States

OM Research LLC

🇺🇸

Lancaster, California, United States

iResearch Atlanta

🇺🇸

Decatur, Georgia, United States

Copley Clinical

🇺🇸

Boston, Massachusetts, United States

Neuroscience Research Institute Inc.

🇺🇸

Winfield, Illinois, United States

Gulfcoast Clinical Research Center

🇺🇸

Fort Myers, Florida, United States

Integrative Clinical Trials

🇺🇸

Brooklyn, New York, United States

Galiz Research

🇺🇸

Hialeah, Florida, United States

APG Research

🇺🇸

Orlando, Florida, United States

PsychCare Consultants Research

🇺🇸

Saint Louis, Missouri, United States

New Life Medical Research Center

🇺🇸

Hialeah, Florida, United States

The University of Chicago Hospitals

🇺🇸

Chicago, Illinois, United States

Comprehensive Psychiatric Care

🇺🇸

Norwich, Connecticut, United States

Innovative Clinical Research, Inc

🇺🇸

Lauderhill, Florida, United States

Adams Clinical

🇺🇸

Watertown, Massachusetts, United States

Clinical Neuroscience Solutions Inc.

🇺🇸

Jacksonville, Florida, United States

Paradigm Research Professionals

🇺🇸

Oklahoma City, Oklahoma, United States

CI Trials

🇺🇸

Santa Ana, California, United States

Manhattan Behavioral Medicine PLLC

🇺🇸

New York, New York, United States

Finger Lakes Clinical Research

🇺🇸

Rochester, New York, United States

Pillar Clinical Research

🇺🇸

Richardson, Texas, United States

SPRI Clinical Trials LLC

🇺🇸

Brooklyn, New York, United States

Cedar Psychiatry

🇺🇸

Springville, Utah, United States

Hospital Provincial de Zamora

🇪🇸

Zamora, Spain

Hospital Universitario Infanta Leonor

🇪🇸

Madrid, Spain

Eastside Therapeutic Resource Inc dba Core Clinical Research

🇺🇸

Everett, Washington, United States

Woodstock Research Center

🇺🇸

Woodstock, Vermont, United States

Consultoria i Projectes Sanitaris S.L. Clinic: Hestia Palau

🇪🇸

Barcelona, Spain

Arch Clinical Trials LLC

🇺🇸

Saint Louis, Missouri, United States

Advanced Clinical Research Center, LLC

🇺🇸

Bridgeton, Missouri, United States

Care Access Research Beverly Hills

🇺🇸

Beverly Hills, California, United States

Viking Clinical Research

🇺🇸

Temecula, California, United States

SF-Care Inc.

🇺🇸

San Rafael, California, United States

CalNeuro Research Group

🇺🇸

Los Angeles, California, United States

The Medical Research Network, LLC

🇺🇸

New York, New York, United States

MindPath Care Centers

🇺🇸

Raleigh, North Carolina, United States

Quest Therapeutics of Avon Lake

🇺🇸

Avon Lake, Ohio, United States

Lindner Center of Hope

🇺🇸

Mason, Ohio, United States

North Star Medical Research LLC

🇺🇸

Middleburg Heights, Ohio, United States

Earle Research

🇺🇸

Houston, Texas, United States

Relaro Medical Trials, LLC

🇺🇸

Dallas, Texas, United States

Grayline Research Center

🇺🇸

Wichita Falls, Texas, United States

Psychiatric Behavioral Solutions

🇺🇸

Salt Lake City, Utah, United States

Vinnitsa National Medical University

🇺🇦

Vinnytsia, Ukraine

Institut Hospital del Mar d'Investigacions Mèdiques - IMIM

🇪🇸

Barcelona, Spain

Hospital Parc Taul Parc Tauli 1

🇪🇸

Sabadell, Barcelona, Spain

Hospital de la Santa Creu i Sant Pau Carrer de Sant Quint

🇪🇸

Barcelona, Spain

Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine

🇺🇦

Kharkiv, Ukraine

Communal Enterprise-Regional Institution of Mental Psychiatric Care of the Poltava Regional Council

🇺🇦

Poltava, Ukraine

Odessa Regional Medical Centre of Mental Health

🇺🇦

Odessa, Ukraine

McLean Hospital

🇺🇸

Belmont, Massachusetts, United States

Kyiv railway clinical hospital 1

🇺🇦

Kyiv, Ukraine

Hassman Research Institute, LLC

🇺🇸

Berlin, New Jersey, United States

Clinical Neuroscience Solutions dba CNS Healthcare

🇺🇸

Orlando, Florida, United States

Carolina Clinical Trials Inc.

🇺🇸

Charleston, South Carolina, United States

Sarkis Clinical Trials

🇺🇸

Gainesville, Florida, United States

New Hope Clinical Research

🇺🇸

Charlotte, North Carolina, United States

Excell Research

🇺🇸

Oceanside, California, United States

Pacific Clinical Research Management Group

🇺🇸

Upland, California, United States

CNS Clinical Research of Coral Springs

🇺🇸

Coral Springs, Florida, United States

Institute for Advanced Medical Research

🇺🇸

Alpharetta, Georgia, United States

AMR Conventions Research

🇺🇸

Naperville, Illinois, United States

Rochester Center for Behavioral Medicine

🇺🇸

Rochester Hills, Michigan, United States

Psychiatric Care and Research Center

🇺🇸

O'Fallon, Missouri, United States

St. Charles Psychiatric Associates dba Midwest Research Group

🇺🇸

Saint Charles, Missouri, United States

Bioscience Research, LLC

🇺🇸

Mount Kisco, New York, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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