A Study to Test Different Doses of BI 1358894 and Find Out Whether They Reduce Symptoms in People With Borderline Personality Disorder

A Phase II Randomized, Double-blinded, Placebo-controlled Parallel Group Trial to Examine the Efficacy and Safety of 4 Oral Doses of BI 1358894 Once Daily Over 12 Week Treatment Period in Patients With Borderline Personality Disorder

This study is open to adults with borderline personality disorder. The purpose of this study is to find out whether a medicine called BI 1358894 helps to reduce symptoms in people with borderline personality disorder. Four different doses of BI 1358894 are tested in the study.

Participants are put into 5 groups by chance. Participants in 4 of the 5 groups take different doses of BI 1358894. Participants in the fifth group take placebo. Participants take BI 1358894 and placebo as tablets once a day. Placebo tablets look like BI 1358894 tablets but do not contain any medicine.

Participants are in the study for about 5 months. During this time, they visit the study site about 12 times and get about 6 phone calls. At the visits, doctors ask participants about their symptoms. The results between the BI 1358894 groups and the placebo group are then compared. The doctors also regularly check the general health of the participants.

Study Overview

• Status: Completed
• Conditions: Borderline Personality Disorder
• Intervention / Treatment: Drug: Placebo; Drug: BI 1358894

• Study Type: Interventional
• Enrollment (Actual): 390
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1133AAH
    • Fundación para el Estudio y Tratamiento de las Enfermedades Mentales (FETEM)
  • Caba, Argentina, C1405BOA
    • Fundación FunDaMos para la asistencia e investigación en psiquiatría
  • Cordoba, Argentina, X5003DCE
    • Instituto Médico DAMIC S.R.L.
  • Cordoba, Argentina, 5004
    • CEN (Centro Especializado Neurociencias)
  • Córdoba, Argentina, X5000FAL
    • Instituto Modelo de Neurología Lennox
  • La Plata, Argentina, 1900
    • Instituto de Neurociencias San Agustín
  • La Plata, Argentina, 1900
    • Clinica Privada de Salud Mental Santa Teresa de Ávila
  • Rosario, Argentina, 2000
    • Instituto Medico de la Fundacion Estudios Clinicos
  • Rosario, Argentina, S2000QJI
    • Centro de Investigación y Asistencia en Psiquiatría (CIAP)
• Australia
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula Therapeutic and Research Group
    • Melbourne, Victoria, Australia, 3004
      • Monash Alfred Psychiatry Research Centre
• Belgium
  • Duffel, Belgium, 2570
    • Universitair Psychiatrisch Centrum Duffel (UPC Duffel)
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • "Filipopolis" - Ambulatory for Group Practice for Specialized Care in Psychiatry
  • Sofia, Bulgaria, 1680
    • Medical Center Intermedica Ltd.
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatement "Alexandrovska" EAD
• Czechia
  • Ostrava-Poruba, Czechia, 708 68
    • MPMeditrine s.r.o.
  • Prague, Czechia, 10000
    • CLINTRIAL s.r.o.
  • Prague, Czechia, 18600
    • INEP Medical s.r.o.
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetsshospital
  • Slagelse, Denmark, 4600
    • Region Zealand, Psychiatric Research Unit
• France
  • Bron, France, 69677
    • HOP Pierre Wertheimer
  • Montpellier, France, 34295
    • HOP la Colombière
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinikum Aachen, AöR
  • Berlin, Germany, 12203
    • Charité - Universitätsmedizin Berlin
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn AöR
  • Gießen, Germany, 35385
    • Universitätsklinikum Gießen und Marburg GmbH
  • Mannheim, Germany, 68159
    • Zentralinstitut für Seelische Gesundheit
  • München, Germany, 80336
    • Klinikum der Universität München - Campus Innenstadt
  • Tübingen, Germany, 72076
    • Universitatsklinikum Tubingen
• Italy
  • Brescia, Italy, 25125
    • IRCCS San Giovanni Di Dio Fatebenefratelli
• Japan
  • Fukuoka, Fukuoka, Japan, 815-0071
    • Kokoro no Clinic Hirao
  • Fukuoka, Kurume, Japan, 830-0033
    • Hirota Clinic
  • Kanagawa, Kawasaki, Japan, 214-0014
    • Kishiro Mental Clinic
  • Kanagawa, Yokohama, Japan, 223-0062
    • Hiyoshi Hospital
  • Nara, Kashihara, Japan, 634-8522
    • Nara Medical University Hospital
  • Tokyo, Chuo-ku, Japan, 103-0012
    • i Kokoro Clinic Nihonbashi
  • Tokyo, Shinjuku-ku, Japan, 162-0843
    • Ichigaya Himorogi Clinic
• Mexico
  • Cdmx, Mexico, 07000
    • GabiPros S.C.
  • Merida, Mexico, 97070
    • Medical Care & Research SA de CV
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr Jose Eleuterio Gonzalez
  • Monterrey, Mexico, 64610
    • CIT-Neuropsique S.C
  • Queretaro, Mexico, 76000
    • Centro de Estudios Clinicos de Queretaro S.C
  • San Luis Potosi, Mexico, 78213
    • BIND Investigaciones S.C.
• Poland
  • Bialystok, Poland, 15-732
    • Podlassian Center of Psychogeriatry, Bialystok
  • Gdansk, Poland, 80-546
    • PI HOUSE Sp. z o.o., Gdansk
• Spain
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocío
  • Valladolid, Spain, 47007
    • CS Casa del Barco
• Sweden
  • Enskede, Sweden, 122 31
    • Psykiatri Södra Stockholm
  • Göteborg, Sweden, 416 50
    • Sahlgrenska Universitetssjukhuset, Östra
  • Uppsala, Sweden, 751 85
    • Akademiska Sjukhuset
• United States
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center, Inc.
    • Temecula, California, United States, 92591
      • Viking Clinical Research, Ltd.
    • Upland, California, United States, 91786
      • Pacific Clinical Research Management Group LLC
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Gulf Coast Clinical Research Center
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Miami, Florida, United States, 33014
      • San Marcus Research Clinic, Inc.
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Institute for Advanced Medical Research
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
  • New York
    • Buffalo, New York, United States, 14215
      • University at Buffalo, The State University of New York
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc.
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Central States Research, LLC
  • Texas
    • Wichita Falls, Texas, United States, 76309
      • Grayline Research Center
  • Washington
    • Everett, Washington, United States, 98201
      • Core Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients meeting diagnostic criteria of borderline personality disorder (BoPD) per Diagnostic and Statistical Manual of Mental Disorders(DSM-5) at screening visit, confirmed by Structured Interview for DSM-5 Personality Disorder (SCID-5-PD).
• Zanarini rating scale for Borderline personality disorder (ZAN-BPD) of ≥ 9 at screening (Visit 1) and randomization (Visit 2), with question #2 Affective Instability score of ≥2.
• Male or female patients, 18-65 years of age at the time of consent

• Women of childbearing potential (WOCBP) able and willing to use two methods of contraception, as confirmed by the investigator, which include one highly effective method of birth control per ICH M3 (R2) that results in a low failure rate of less than 1%, plus one barrier method.

  --A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tubal occlusion/ ligation is NOT a method of permanent sterilization. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.

• Signed and dated written informed consent in accordance with International Council on Harmonization (ICH) - Good Clinical Practice (GCP) and local legislation prior to admission to the trial.
• further inclusion criteria apply.

Exclusion Criteria:

• Current diagnosis of paranoid, schizoid, schizotypal and antisocial personality disorders, as confirmed by SCID-5-PD at screening visit.
• Lifetime diagnosis for schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar I disorder, or delusional disorder as confirmed by the SCID-5 at the screening visit.
• Any other mental disorder that is the primary focus of treatment in the last 6 months prior to randomization, as per the clinical judgement of the investigator.
• Inpatient stay or hospitalization due to worsening of BoPD within 3 months prior to randomization.
• Initiation or change in any type or frequency of psychotherapy for BoPD within the last 3 months prior to screening.
• Any ongoing use of psychotropic medications within 7 days prior to randomization or during the course of study.
• Any suicidal behavior in the past 1 year.
• Any suicidal ideation of type 4 or 5 in the Columbia Suicidal Severity Rating Scale (C-SSRS) in the past 3 months.
• further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Film-coated tablet
Experimental: BI 1358894 5mg	Drug: BI 1358894; Film-coated tablet
Experimental: BI 1358894 25mg	Drug: BI 1358894; Film-coated tablet
Experimental: BI 1358894 75mg	Drug: BI 1358894; Film-coated tablet
Experimental: BI 1358894 125mg	Drug: BI 1358894; Film-coated tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in ZANarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Total Score at Week 10	The ZAN-BPD scale reflects the nine DSM-5 criteria and the scale has 4 domain scores that reflect core areas of BPD (i.e., affective, cognitive, impulsive and interpersonal symptoms). The ZAN-BPD scale includes a 5-point rating scale (i.e., 0 = no symptoms to 4 = severe symptoms) for each criterion. The total ZAN-BPD score is the sum of the 4 domain scores and ranges from 0 to 36 where higher scores mean severe symptoms. Least Squares (LS) mean and standard error were estimated by restricted maximum likelihood-based mixed effects model repeated measures (REML-based MMRM) including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8 and 10) and the baseline ZAN-BPD total score strata indicator (<=18 vs. >=19), the continuous fixed covariate of baseline ZAN-BPD total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. LS mean (standard error) for Week 10 are reported.	The change from baseline at Week 10 in the total ZAN-BPD score was calculated using the MMRM model which is a longitudinal analyses and it incorporates ZAN-BPD measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ZANarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Response: Defined as ≥30% ZAN-BPD Reduction From Baseline at Week 10	Number of participants with ZAN-BPD response is reported. ZAN-BPD response was defined as ≥30% ZAN-BPD reduction from baseline at Week 10. The ZAN-BPD scale reflects the nine DSM-5 criteria, and the scale has 4 domain scores that reflect core areas of BPD (i.e., affective, cognitive, impulsive and interpersonal symptoms). The ZAN-BPD scale includes a 5-point rating scale (i.e., 0 = no symptoms to 4 = severe symptoms) for each criterion. The total ZAN-BPD score is the sum of the 4 domain scores and ranges from 0 to 36 where higher scores mean severe symptoms.	Baseline and at Week 10.
Change From Baseline in Difficulties in Emotion Regulation Scale (DERS-16) Total Score at Week 10	The DERS is a self-report measure of emotion regulation difficulties. It consists of 16 items that assess non-acceptance of negative emotions, inability to engage in goal-directed behaviors when distressed, difficulties controlling impulsive behaviors when distressed, limited access to emotion regulation strategies perceived as effective, and lack of emotional clarity. Each item is scored from 1 (almost never (0-10%)) to 5 (almost always (91-100%)). Total DERS-16 can range from 16 to 80, with higher scores reflecting greater levels of emotion dysregulation. Least Squares (LS) mean and standard error were estimated by REML-based MMRM including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8 and 10) and the continuous fixed covariate of baseline DERS-16 total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. Patient was considered as random. LS mean (standard error) for Week 10 are reported.	Change from baseline in DERS-16 total score at Week 10 was calculated using the MMRM model which is a longitudinal analyses and it incorporates DERS-16 measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.
Change From Baseline in State-Trait Anxiety Inventory (STAI-S) Total Score at Week 10	The STAI-S consists of 20 item state anxiety questions that evaluate how respondents feel "right now, at this moment". All items are rated on a weighted score of 1 to 4 scale (e.g. from 'Almost Never to 'Almost Always'); with higher scores indicating greater anxiety. STAI-S score ranges from 20 to 80 where higher scores indicate greater anxiety. Least Squares (LS) mean and standard error were estimated by restricted maximum likelihood-based mixed effects model repeated measures (REML-based MMRM) including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 10) and the continuous fixed covariate of baseline STAI-S total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. Patient was considered as random. LS mean (standard error) for Week 10 are reported.	Change from baseline in STAI-S total score at Week 10 was calculated using the MMRM model which is a longitudinal analyses and it incorporates STAI-S measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.
Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Week 10	The PHQ-9 is a 9-item brief self-reported tool used for screening, diagnosing, monitoring and measuring the severity of depression. PHQ-9 has a maximum total score of 27. Depression Severity is assessed as: none (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), or severe (20-27). Least Squares (LS) mean and standard error were estimated by restricted maximum likelihood-based mixed effects model repeated measures (REML-based MMRM) including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 10) and the continuous fixed covariate of baseline PHQ-9 total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. Patient was considered as random. LS mean (standard error) for Week 10 are reported.	Change from baseline in PHQ-9 total score at Week 10 was calculated using the MMRM model which is a longitudinal analyses and it incorporates PHQ-9 measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) at Week 10	The CGI-S rating scale measures the clinician's impression of the severity of illness exhibited by a participant. The CGI-S only question states "Considering your total clinical experience with this particular population, please choose the response below that best describes how mentally ill the patient was over the past week?", and is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. Least Squares (LS) mean and standard error were estimated by REML-based MMRM including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 10) and the continuous fixed covariate of baseline CGI-S total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. Patient was considered as random. LS mean (standard error) for Week 10 are reported.	Change from baseline in CGI-S scale at Week 10 was calculated using the MMRM model which is a longitudinal analyses and it incorporates CGI-S measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.
Change From Baseline in Patient Global Impression Severity Scale (PGI-S) at Week 10	The PGI-S measures the patient's impression of the severity of their illness. It is a single item 5-point scale that asks patients to rate the severity of their illness. The PGI-S question states "Please choose the response below that best describes the overall severity of your symptoms of Borderline Personality Disorder at this time. (Select one response)": 1=No symptoms; 2=Mild; 3=Moderate; 4=Severe; 5=Very severe. Least Squares (LS) mean and standard error were estimated by restricted maximum likelihood-based mixed effects model repeated measures (REML-based MMRM) including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8,10) and the continuous fixed covariate of baseline PGI-S total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. Patient was considered as random. LS means (standard error) for Week 10 are reported.	Change from baseline in PGI-S scale at Week 10 was calculated using the MMRM model which is a longitudinal analyses and it incorporates PGI-S measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): December 9, 2022
• Study Completion (Actual): January 25, 2023

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Borderline Personality Disorder
• Other Study ID Numbers: 1402-0012; 2020-000078-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'.For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• 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