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

Borderline Personality Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04566601
• Other study ID #: 1402-0012
• Secondary ID: 2020-000078-12
• Status: Completed
• Phase: Phase 2
• Start date: November 13, 2020
• Est. completion date: January 25, 2023

Study information

• Verified date: January 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 390
• Est. completion date: January 25, 2023
• Est. primary completion date: December 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Borderline Personality Disorder
• Personality Disorders

Intervention

Drug:
• BI 1358894
Film-coated tablet
• Placebo
Film-coated tablet

Locations

Country	Name	City	State
Argentina	Fundación FunDaMos para la asistencia e investigación en psiquiatría	Caba
Argentina	Fundación para el Estudio y Tratamiento de las Enfermedades Mentales (FETEM)	Caba
Argentina	CEN (Centro Especializado Neurociencias)	Cordoba
Argentina	Instituto Médico DAMIC S.R.L.	Cordoba
Argentina	Instituto Modelo de Neurología Lennox	Córdoba
Argentina	Clinica Privada de Salud Mental Santa Teresa de Avila	La Plata
Argentina	Instituto de Neurociencias San Agustín	La Plata
Argentina	Centro de Investigacion y Asistencia en Psiquiatria (CIAP)	Rosario
Argentina	Instituto Médico de la Fundación Estudios Clínicos	Rosario
Australia	Peninsula Therapeutic and Research Group	Frankston	Victoria
Australia	Monash Alfred Psychiatry Research Centre	Melbourne	Victoria
Belgium	Universitair Psychiatrisch Centrum Duffel (UPC Duffel)	Duffel
Bulgaria	"Filipopolis" - Ambulatory for Group Practice for Specialized Care in Psychiatry	Plovdiv
Bulgaria	Medical Center Intermedica Ltd.	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatement "Alexandrovska" EAD	Sofia
Czechia	MPMeditrine s.r.o.	Ostrava-Poruba
Czechia	Clintrial s.r.o.	Prague
Czechia	INEP medical s.r.o.	Prague
Denmark	Aalborg Universitetsshospital	Aalborg
Denmark	Region Zealand, Psychiatric Research Unit	Slagelse
France	HOP Pierre Wertheimer	Bron
France	HOP la Colombière	Montpellier
Germany	Universitätsklinikum Aachen, AöR	Aachen
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Bonn AöR	Bonn
Germany	Universitätsklinikum Gießen und Marburg GmbH	Gießen
Germany	Zentralinstitut für seelische Gesundheit	Mannheim
Germany	Klinikum der Universität München - Campus Innenstadt	München
Germany	Universitätsklinikum Tübingen	Tübingen
Italy	IRCCS San Giovanni Di Dio Fatebenefratelli	Brescia
Japan	Kokoro no Clinic Hirao	Fukuoka, Fukuoka
Japan	Hirota Clinic	Fukuoka, Kurume
Japan	Kishiro Mental Clinic	Kanagawa, Kawasaki
Japan	Hiyoshi Hospital	Kanagawa, Yokohama
Japan	Nara Medical University Hospital	Nara, Kashihara
Japan	i Kokoro Clinic Nihonbashi	Tokyo, Chuo-ku
Japan	Ichigaya Himorogi Clinic	Tokyo, Shinjuku-ku
Mexico	GabiPros S.C.	Cdmx
Mexico	Medical Care & Research SA de CV	Merida
Mexico	CIT-Neuropsique S.C	Monterrey
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez	Monterrey
Mexico	Centro de Estudios Clinicos de Queretaro S.C	Queretaro
Mexico	BIND Investigaciones S.C.	San Luis Potosi
Poland	Podlassian Center of Psychogeriatry, Bialystok	Bialystok
Poland	PI HOUSE Sp. z o.o., Gdansk	Gdansk
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Virgen del Rocío	Sevilla
Spain	CS Casa del Barco	Valladolid
Sweden	Psykiatri Södra Stockholm	Enskede
Sweden	Sahlgrenska Universitetssjukhuset, Östra	Göteborg
Sweden	Akademiska sjukhuset	Uppsala
United States	Institute for Advanced Medical Research	Alpharetta	Georgia
United States	Advanced Research Center, Inc.	Anaheim	California
United States	McLean Hospital	Belmont	Massachusetts
United States	University at Buffalo, The State University of New York	Buffalo	New York
United States	Neurobehavioral Research, Inc.	Cedarhurst	New York
United States	Center For Emotional Fitness	Cherry Hill	New Jersey
United States	Core Clinical Research	Everett	Washington
United States	Precise Research Centers	Flowood	Mississippi
United States	Gulf Coast Clinical Research Center	Fort Myers	Florida
United States	Sarkis Clinical Trials	Gainesville	Florida
United States	San Marcus Research Clinic, Inc.	Miami	Florida
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Viking Clinical Research, Ltd.	Temecula	California
United States	Central States Research, LLC	Tulsa	Oklahoma
United States	Pacific Clinical Research Management Group LLC	Upland	California
United States	Grayline Research Center	Wichita Falls	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Bulgaria,  Czechia,  Denmark,  France,  Germany,  Italy,  Japan,  Mexico,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

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