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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-000078-12 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 1358894 5mg | Experimental |
| |
| BI 1358894 25mg | Experimental |
| |
| BI 1358894 75mg | Experimental |
| |
| BI 1358894 125mg | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 1358894 | Drug | Film-coated tablet |
|
| 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. |
| 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. |
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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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Advanced Research Center, Inc. | Anaheim | California | 92805 | United States | ||
| Viking Clinical Research, Ltd. |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39832346 | Derived | Dwyer JB, Schmahl C, Makinodan M, Fineberg SK, Sommer S, Wruck J, Jelaska A, Adeniji A, Goodman M. Efficacy and Safety of BI 1358894 in Patients With Borderline Personality Disorder: Results of a Phase 2 Randomized, Placebo-Controlled, Parallel Group Dose-Ranging Trial. J Clin Psychiatry. 2025 Jan 13;86(1):24m15523. doi: 10.4088/JCP.24m15523. | |
| 36375174 |
| Label | URL |
|---|---|
| Related Info | View source |
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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.
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.
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'.
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
This was a Phase II, 12-week multicenter, multinational, randomised, double-blind, placebo-controlled, parallel-group trial in patients with borderline personality disorder (BPD). Eligible patients with BPD were randomised to receive either BI 1358894 or placebo in a 2.5:1:1:1:2 ratio (placebo or BI 1358894 5 milligram (mg), 25 mg, 75 mg, or 125 mg), for 12 weeks.
This trial included a screening period, a 12-week randomised treatment period, and a 4-week follow-up period.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| FG001 | BI 1358894 5mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 23, 2022 | Dec 6, 2023 |
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| Placebo | Drug | Film-coated tablet |
|
| 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. |
| Temecula |
| California |
| 92591 |
| United States |
| Pacific Clinical Research Management Group LLC | Upland | California | 91786 | United States |
| Yale University School of Medicine | New Haven | Connecticut | 06519 | United States |
| Gulf Coast Clinical Research Center | Fort Myers | Florida | 33912 | United States |
| Sarkis Clinical Trials | Gainesville | Florida | 32607 | United States |
| San Marcus Research Clinic, Inc. | Miami | Florida | 33014 | United States |
| Institute for Advanced Medical Research | Alpharetta | Georgia | 30022 | United States |
| McLean Hospital | Belmont | Massachusetts | 02478 | United States |
| Precise Research Centers | Flowood | Mississippi | 39232 | United States |
| Center For Emotional Fitness | Cherry Hill | New Jersey | 08002 | United States |
| University at Buffalo, The State University of New York | Buffalo | New York | 14215 | United States |
| Neurobehavioral Research, Inc. | Cedarhurst | New York | 11516 | United States |
| Central States Research, LLC | Tulsa | Oklahoma | 74136 | United States |
| Grayline Research Center | Wichita Falls | Texas | 76309 | United States |
| Core Clinical Research | Everett | Washington | 98201 | United States |
| Fundación para el Estudio y Tratamiento de las Enfermedades Mentales (FETEM) | CABA | C1133AAH | Argentina |
| Fundación FunDaMos para la asistencia e investigación en psiquiatrÃa | CABA | C1405BOA | Argentina |
| CEN (Centro Especializado Neurociencias) | Córdoba | 5004 | Argentina |
| Instituto Modelo de NeurologÃa Lennox | Córdoba | X5000FAL | Argentina |
| Instituto Médico DAMIC S.R.L. | Córdoba | X5003DCE | Argentina |
| Clinica Privada de Salud Mental Santa Teresa de Avila | La Plata | 1900 | Argentina |
| Instituto de Neurociencias San AgustÃn | La Plata | 1900 | Argentina |
| Instituto Médico de la Fundación Estudios ClÃnicos | Rosario | 2000 | Argentina |
| Centro de Investigacion y Asistencia en Psiquiatria (CIAP) | Rosario | S2000QJI | Argentina |
| Peninsula Therapeutic and Research Group | Frankston | Victoria | 3199 | Australia |
| Monash Alfred Psychiatry Research Centre | Melbourne | Victoria | 3004 | Australia |
| Universitair Psychiatrisch Centrum Duffel (UPC Duffel) | Duffel | 2570 | Belgium |
| "Filipopolis" - Ambulatory for Group Practice for Specialized Care in Psychiatry | Plovdiv | 4000 | Bulgaria |
| University Multiprofile Hospital for Active Treatement "Alexandrovska" EAD | Sofia | 1431 | Bulgaria |
| Medical Center Intermedica Ltd. | Sofia | 1680 | Bulgaria |
| MPMeditrine s.r.o. | Ostrava-Poruba | 708 68 | Czechia |
| Clintrial s.r.o. | Prague | 10000 | Czechia |
| INEP medical s.r.o. | Prague | 18600 | Czechia |
| Aalborg Universitetsshospital | Aalborg | 9000 | Denmark |
| Region Zealand, Psychiatric Research Unit | Slagelse | 4600 | Denmark |
| HOP Pierre Wertheimer | Bron | 69677 | France |
| HOP la Colombière | Montpellier | 34295 | France |
| Universitätsklinikum Aachen, AöR | Aachen | 52074 | Germany |
| Charité - Universitätsmedizin Berlin | Berlin | 12203 | Germany |
| Universitätsklinikum Bonn AöR | Bonn | 53127 | Germany |
| Universitätsklinikum Gießen und Marburg GmbH | Giessen | 35385 | Germany |
| Zentralinstitut für seelische Gesundheit | Mannheim | 68159 | Germany |
| Klinikum der Universität München - Campus Innenstadt | München | 80336 | Germany |
| Universitätsklinikum Tübingen | Tübingen | 72076 | Germany |
| IRCCS San Giovanni Di Dio Fatebenefratelli | Brescia | 25125 | Italy |
| Kokoro no Clinic Hirao | Fukuoka, Fukuoka | 815-0071 | Japan |
| Hirota Clinic | Fukuoka, Kurume | 830-0033 | Japan |
| Kishiro Mental Clinic | Kanagawa, Kawasaki | 214-0014 | Japan |
| Hiyoshi Hospital | Kanagawa, Yokohama | 223-0062 | Japan |
| Nara Medical University Hospital | Nara, Kashihara | 634-8522 | Japan |
| i Kokoro Clinic Nihonbashi | Tokyo, Chuo-ku | 103-0012 | Japan |
| Ichigaya Himorogi Clinic | Tokyo, Shinjuku-ku | 162-0843 | Japan |
| GabiPros S.C. | Mexico City | 07000 | Mexico |
| Medical Care & Research SA de CV | Mérida | 97070 | Mexico |
| Hospital Universitario Dr Jose Eleuterio Gonzalez | Monterrey | 64460 | Mexico |
| CIT-Neuropsique S.C | Monterrey | 64610 | Mexico |
| Centro de Estudios Clinicos de Queretaro S.C | Querétaro | 76000 | Mexico |
| BIND Investigaciones S.C. | San Luis Potosà City | 78213 | Mexico |
| Podlassian Center of Psychogeriatry, Bialystok | Bialystok | 15-732 | Poland |
| PI HOUSE Sp. z o.o., Gdansk | Gdansk | 80-546 | Poland |
| Hospital Universitario Marqués de Valdecilla | Santander | 39008 | Spain |
| Hospital Virgen del RocÃo | Seville | 41013 | Spain |
| CS Casa del Barco | Valladolid | 47007 | Spain |
| Psykiatri Södra Stockholm | Enskede | 122 31 | Sweden |
| Sahlgrenska Universitetssjukhuset, Östra | Gothenburg | 416 50 | Sweden |
| Akademiska sjukhuset | Uppsala | 751 85 | Sweden |
| 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. |
Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| FG002 | BI 1358894 25mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| FG003 | BI 1358894 75mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg. |
| FG004 | BI 1358894 125mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg. |
| COMPLETED | Completed planned trial treatment of 12 weeks. |
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| NOT COMPLETED |
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Treated Set (TS) consisted of all patients who were randomised and that received at least one administration of trial medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| BG001 | BI 1358894 5mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| BG002 | BI 1358894 25mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| BG003 | BI 1358894 75mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg. |
| BG004 | BI 1358894 125mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| ZAN-BPD total score at Baseline | The ZANarini rating scale for Borderline Personality Disorder (ZAN-BPD) reflects the nine DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) 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. | Mean | Standard Deviation | score on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a ZAN-BPD score value at baseline and one ZAN-BPD score value at one of the post-baseline timepoints up to Week 10. | Posted | Least Squares Mean | Standard Error | units on a scale | 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. |
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| 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. | Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Only participants with ZAN-BPD total score at baseline and at Week 10 are reported. | Posted | Count of Participants | Participants | Baseline and at Week 10. |
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| 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. | Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a DERS-16 total score value at baseline and a DERS-16 total score value at one of the post-baseline timepoints up to Week 10. | Posted | Least Squares Mean | Standard Error | units on a scale | 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. |
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| 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. | Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a STAI-S total score value at baseline and a STAI-S total score value at one of the post-baseline timepoints up to Week 10. | Posted | Least Squares Mean | Standard Error | units on a scale | 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. |
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| 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. | Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a PHQ-9 total score value at baseline and a PHQ-9 total score value at one of the post-baseline timepoints up to Week 10. | Posted | Least Squares Mean | Standard Error | units on a scale | 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. |
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| 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. | Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a CGI-S scale value at baseline and a CGI-S scale value at one of the post-baseline timepoints up to Week 10. | Posted | Least Squares Mean | Standard Error | units on a scale | 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. |
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| 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. | Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a PGI-S scale value at baseline and a PGI-S scale value at one of the post-baseline timepoints up to Week 10. | Posted | Least Squares Mean | Standard Error | units on a scale | 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. |
|
From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks.
Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. | 0 | 128 | 11 | 128 | 75 | 128 |
| EG001 | BI 1358894 5mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. | 0 | 52 | 4 | 52 | 32 | 52 |
| EG002 | BI 1358894 25mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. | 0 | 53 | 3 | 53 | 40 | 53 |
| EG003 | BI 1358894 75mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg. | 0 | 53 | 4 | 53 | 34 | 53 |
| EG004 | BI 1358894 125mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg. | 2 | 104 | 16 | 104 | 61 | 104 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myocardial infarction | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cannabinoid hyperemesis syndrome | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oesophageal varices haemorrhage | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Jaundice cholestatic | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Hepatitis A | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Wound abscess | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Comminuted fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Forearm fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Metabolic acidosis | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 25.1 | Systematic Assessment |
| |
| Aggression | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Drug abuse | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Panic attack | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Post-traumatic stress disorder | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Suicidal behaviour | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Calculus urinary | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperinsulinaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Increased appetite | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Initial insomnia | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Intentional self-injury | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 26, 2023 | Dec 6, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D001883 | Borderline Personality Disorder |
| ID | Term |
|---|---|
| D010554 | Personality Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000730434 | TRPC inhibitor BI 1358894 |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg. |
| Other |
No formal hypotheses were tested. |
| Least Squares (LS) mean difference and 95 % confidence interval 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 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 means differences (95 % confidence intervals) for Week 10 are reported. | Mixed effects model repeated measures | 0.6014 | P-value is considered nominal. | Mean Difference (Net) | -0.6 | 2-Sided | 95 | -2.60 | 1.51 | Least Squares Mean of "BI 1358894 25mg" - Least Squares Mean of "Placebo". | Other | No formal hypotheses were tested. |
| Least Squares (LS) mean difference and 95 % confidence interval 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 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 means differences (95 % confidence intervals) for Week 10 are reported. | Mixed effects model repeated measures | 0.8166 | P-value is considered nominal. | Mean Difference (Net) | -0.2 | 2-Sided | 95 | -2.17 | 1.72 | Least Squares Mean of "BI 1358894 75mg" - Least Squares Mean of "Placebo". | Other | No formal hypotheses were tested. |
| Least Squares (LS) mean difference and 95 % confidence interval 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 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 means differences (95 % confidence intervals) for Week 10 are reported. | Mixed effects model repeated measures | 0.6588 | P-value is considered nominal. | Mean Difference (Net) | -0.4 | 2-Sided | 95 | -1.96 | 1.24 | Least Squares Mean of "BI 1358894 125mg" - Least Squares Mean of "Placebo". | Other | No formal hypotheses were tested. |
| A flat vs. non-flat dose-response relationship across the 4 doses of BI 1358894 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, exponential, Emax 1, Emax 2 and Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.100). | MCP-Mod sigmoid Emax model fit | Model assumption: 50% of the maximum effect is achieved at 25 mg, and 90% of the maximum effect is achieved at 75 mg. | 0.3914 | Other | MMRM estimates were used as input for the MCP-Mod. MMRM included the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 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. |
| A flat vs. non-flat dose-response relationship across the 4 doses of BI 1358894 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, exponential, Emax 1, Emax 2 and Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.100). | MCP-Mod Emax1 model fit | Model assumption: 50% of the maximum effect is achieved at 25 mg. | 0.4104 | Other | MMRM estimates were used as input for the MCP-Mod. MMRM included the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 10 and 12) 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. |
| A flat vs. non-flat dose-response relationship across the 4 doses of BI 1358894 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, exponential, Emax 1, Emax 2 and Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.100). | MCP-Mod linear model fit | Model assumption: No parameter assumptions required. | 0.4560 | Other | MMRM estimates were used as input for the MCP-Mod. MMRM included the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 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. |
| A flat vs. non-flat dose-response relationship across the 4 doses of BI 1358894 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, exponential, Emax 1, Emax 2 and Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.100). | MCP-Mod exponential model fit | Model assumption: 5% of the maximum effect is achieved at 25 mg. | 0.4908 | Other | MMRM estimates were used as input for the MCP-Mod. MMRM included the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 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. |
| A flat vs. non-flat dose-response relationship across the 4 doses of BI 1358894 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, exponential, Emax 1, Emax 2 and Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.100). | MCP-Mod Emax2 model fit | Model assumption: 70% of the maximum effect is achieved at 5 mg. | 0.4974 | Other | MMRM estimates were used as input for the MCP-Mod. MMRM included the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 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. |
| OG002 | BI 1358894 25mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG003 | BI 1358894 75mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg. |
| OG004 | BI 1358894 125mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg. |
|
|
|
| Placebo |
Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG001 | BI 1358894 5mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG002 | BI 1358894 25mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG003 | BI 1358894 75mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg. |
| OG004 | BI 1358894 125mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg. |
|
|
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Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.
| OG001 | BI 1358894 5mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG002 | BI 1358894 25mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG003 | BI 1358894 75mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg. |
| OG004 | BI 1358894 125mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg. |
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| OG001 | BI 1358894 5mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG002 | BI 1358894 25mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG003 | BI 1358894 75mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg. |
| OG004 | BI 1358894 125mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg. |
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Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG001 | BI 1358894 5mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG002 | BI 1358894 25mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG003 | BI 1358894 75mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg. |
| OG004 | BI 1358894 125mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg. |
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Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.
| OG001 | BI 1358894 5mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG002 | BI 1358894 25mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg. |
| OG003 | BI 1358894 75mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg. |
| OG004 | BI 1358894 125mg | Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg. |
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