A Study to Test the Effect of Different Doses of BI 1358894 and Quetiapine in People With Depression
A Phase II, 6-week, Multicenter, Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel Group Trial With a Quetiapine Arm to Evaluate the Efficacy, Tolerability and Safety of Oral BI 1358894 in Patients With Major Depressive Disorder With Inadequate Response to Antidepressants.
2 other identifiers
interventional
389
14 countries
120
Brief Summary
This study is open to adults with depression (major depressive disorder) for whom standard treatment with antidepressants alone does not work sufficiently. The purpose of the trial is to find out whether a medicine called BI 1358894 helps to improve symptoms of depression. Four different doses of BI 1358894 are tested in the study. Participants continue their standard antidepressant therapy throughout the study. Participants are put into 6 groups by chance. Participants in 4 of the 6 groups take different doses of BI 1358894, and placebo. Participants in the fifth group take quetiapine, a medicine already used to treat depression, and placebo. Participants in the sixth group take placebo only. Participants take BI 1358894, quetiapine, or placebo as tablets. Placebo tablets look like BI 1358894 or quetiapine tablets but do not contain any medicine. Each participant takes tablets twice a day. Participants are in the study for about 3 months. During this time, they visit the study site about 8 times and get about 2 phone calls. At the visits, doctors ask participants about their symptoms. The results between the BI 1358894 groups, the quetiapine group, and the placebo group are then compared. The doctors also regularly check the general health of the participants.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Nov 2020
Typical duration for phase_2
120 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 18, 2020
CompletedFirst Posted
Study publicly available on registry
August 20, 2020
CompletedStudy Start
First participant enrolled
November 20, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 10, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
February 2, 2024
CompletedResults Posted
Study results publicly available
March 6, 2025
CompletedMarch 6, 2025
February 1, 2025
3.1 years
August 18, 2020
January 13, 2025
February 17, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6
Change from baseline in MADRS total score at Week 6 is reported. The MADRS evaluates core symptoms of depression and consists of 10 items. Nine of them are based upon participant reports, and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). The possible total score could range from 0 (normal with absence of symptoms) to 60 (severe depression). Least squares mean and adjusted standard error were estimated by Restricted Maximum Likelihood (REML)-based Mixed effects model for repeated measures (MMRM) including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline MADRS total score. Visit was treated as a repeated measure with an unstructured covariance matrix. The Kenward-Roger approximation was used to estimate the denominator degrees of freedom and adjust standard errors.
MMRM included measurements from baseline (Week 0) and at Weeks 1, 2, 4 and 6 after first drug administration. MMRM estimates of change from baseline to Week 6 is reported.
Secondary Outcomes (4)
Number of Participants With Response Defined as ≥ 50% Montgomery-Åsberg Depression Rating Scale (MADRS) Reduction From Baseline at Week 6
Prior to the first intake of the trial medication (week 0, baseline) and after 6 weeks of treatment.
Change From Baseline in State-Trait Anxiety Inventory (STAI) State and Trait Version Scores at Week 6
MMRM included measurements from baseline (Week 0) and at Weeks 1, 2, 4 and 6 after first drug administration. MMRM estimates of change from baseline to Week 6 is reported.
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 6
MMRM included measurements from baseline (Week 0) and at Weeks 1, 2, 4 and 6 after first drug administration. MMRM estimates of change from baseline to Week 6 is reported.
Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6
MMRM included measurements from baseline (Week 0) and at Weeks 1, 2, 4 and 6 after first drug administration. MMRM estimates of change from baseline to Week 6 is reported.
Study Arms (6)
5 mg BI 1358894
EXPERIMENTALParticipants with an established diagnosis of MDD administered one 5 milligram (mg) dose of BI 1358894 in the morning as film-coated tablet, and one dose of placebo matching quetiapine in the evening as tablets. Each administration was performed orally once daily, for 6 weeks. During the trial, participants also continued treatment with their OAD.
Placebo
PLACEBO COMPARATORParticipants with an established diagnosis of Major Depressive Disorder (MDD) administered one dose of placebo matching BI 1358894 in the morning as film-coated tablets, and one dose of placebo matching quetiapine in the evening as tablets. Each administration was performed orally once daily, for 6 weeks. During the trial, participants also continued treatment with their Ongoing Antidepressants (OAD).
Quetiapine
ACTIVE COMPARATORParticipants with an established diagnosis of MDD administered one dose of placebo matching BI 1358894 in the morning as film-coated tablets, and one 150 or 300 mg dose of quetiapine in the evening as tablets. Each administration was performed orally once daily, for 6 weeks. The daily active dose at the start of therapy was 50 mg on Day 1, 100 mg at Day 2 and 150 mg on Day 3 and 4. Beginning with Day 5, the recommended daily dose of 300 mg was taken. If not tolerated by a participant, the dose was reduced to 150 mg in Week 1. Thereafter, this finally chosen dose had to be stable until end of treatment at Week 6. During the trial, participants also continued treatment with their OAD.
25 mg BI 1358894
EXPERIMENTALParticipants with an established diagnosis of MDD administered one 25 mg dose of BI 1358894 in the morning as film-coated tablet, and one dose of placebo matching quetiapine in the evening as tablets. Each administration was performed orally once daily, for 6 weeks. During the trial, participants also continued treatment with their OAD.
75 mg BI 1358894
EXPERIMENTALParticipants with an established diagnosis of MDD administered one 75 mg dose of BI 1358894 in the morning as film-coated tablets, and one dose of placebo matching quetiapine in the evening as tablets. Each administration was performed orally once daily, for 6 weeks. During the trial, participants also continued treatment with their OAD.
125 mg BI 1358894
EXPERIMENTALParticipants with an established diagnosis of MDD administered one 125 mg dose of BI 1358894 in the morning as film-coated tablets, and one dose of placebo matching quetiapine in the evening as tablets. Each administration was performed orally once daily, for 6 weeks. During the trial, participants also continued treatment with their OAD.
Interventions
Eligibility Criteria
You may qualify if:
- Established diagnosis of Major Depressive Disorder (MDD), single episode or recurrent, as confirmed at the time of screening by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 5th version (DSM-5) (SCID-5), with a duration of current depressive episode ≥ 8 weeks and ≤ 24 months at the time of screening visit
- Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 24 at screening, as confirmed by a trained site based rater AND interactive, computer administered MADRS. The difference in the rater and computer administered MADRS must not exceed more than 7 points (for details refer to section 6.2). In addition, trial participants must have a score of ≥ 3 on the Reported Sadness Item on both MADRS scales (computer administered and rater-administered MADRS)
- A documented ongoing monotherapy treatment of ≥ 4 weeks at the screening visit, with bupropion or a protocol specified Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin Norepinephrine Reuptake Inhibitor (SNRI) (refer to the ISF) at adequate dose (at least minimum effective dose as per prescribing information and as confirmed per detectable drug levels in the screening blood or urine sampling)
- Male and female participants, 18 to 65 years of age, both inclusively at the time of consent
- Women who are of child-bearing potential (WOCBP)1 must be able and willing, as confirmed by the investigator, to use two methods of contraception which include one highly effective method of birth control per ICH M3 (R2) that result in a low failure rate of less than 1%, plus one additional barrier
- Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
- Able to communicate well, and to understand and comply with trial requirements
You may not qualify if:
- Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar disorder, delusional disorder or MDD with psychotic features as assessed by the Structured Clinical Interview for DSM-5 Clinical Trials (SCID-5) at the time of screening
- Diagnosis with antisocial, paranoid, schizoid or schizotypal personality disorder as per DSM-5 criteria, at the time of screening visit. Any other personality disorder at screening visit that significantly affects current psychiatric status and likely to impact trial participation, as per the judgement of investigator
- Diagnosis of a substance related disorder within 3 months prior to screening visit (with exception of caffeine and tobacco)
- History of seizure disorders, stroke, brain tumor or any other major neurological illness that can impact participation in the trial
- Any suicidal behavior in the past 12 months prior to screening (per investigator judgement including an actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)
- Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (CSSRS) in the past 3 months prior to screening or at screening or baseline visit (i.e. active suicidal thought with method and intent but without specific plan, or active suicidal thought with method, intent and plan)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (120)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Collaborative Neuroscience Network, LLC (CNS)
Garden Grove, California, 92845, United States
Alliance Research
Long Beach, California, 90807, United States
Asclepes Research Centers
Sherman Oaks, California, 91403, United States
California Neuroscience Research
Sherman Oaks, California, 91403, United States
Schuster Medical Research Institute
Sherman Oaks, California, 91403, United States
Viking Clinical Research, Ltd.
Temecula, California, 92591, United States
Collaborative Neuroscience Research, LLC
Torrance, California, 90504, United States
Mountain Mind. LLC
Denver, Colorado, 80202, United States
CT Clinical Research
Cromwell, Connecticut, 06416, United States
Institute of Living
Hartford, Connecticut, 06106, United States
Gulf Coast Clinical Research Center
Fort Myers, Florida, 33912, United States
Sarkis Clinical Trials
Gainesville, Florida, 32607, United States
Clinical Neuroscience Solutions, Inc
Jacksonville, Florida, 32256, United States
Optimus U Corporation
Miami, Florida, 33135, United States
Advanced Discovery Research LLC
Atlanta, Georgia, 30318, United States
Atlanta Center
Atlanta, Georgia, 30331, United States
Chicago Research Center, Incorporated
Chicago, Illinois, 60634, United States
University of Kansas School of Medicine-Wichita
Wichita, Kansas, 67214, United States
Precise Research Centers
Flowood, Mississippi, 39232, United States
Psychiatric Care and Research Center
O'Fallon, Missouri, 63368, United States
Center For Emotional Fitness
Cherry Hill, New Jersey, 08002, United States
Hassman Research Institute
Marlton, New Jersey, 08053, United States
Synexus Clinical Research US, Inc.
New York, New York, 10017, United States
University of Cincinnati
Cincinnati, Ohio, 45219, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210, United States
Lehigh Center for Clinical Research
Allentown, Pennsylvania, 18104, United States
Global Medical Institutes, LLC, Scranton Medical Institute
Moosic, Pennsylvania, 18507, United States
Core Clinical Research
Everett, Washington, 98201, United States
Fundación para el Estudio y Tratamiento de las Enfermedades Mentales (FETEM)
CABA, C1133AAH, Argentina
CEN (Centro Especializado Neurociencias)
Córdoba, 5004, Argentina
Instituto DAMIC - Fundacion Rusculleda
Córdoba, X5003DCE, Argentina
CENPIA-Centro de Estudios Neuropsiquiátricos y Psicológicos Integral Ambulatorio
La Plata, 1900, Argentina
Clinica Privada de Salud Mental Santa Teresa de Avila
La Plata, 1900, Argentina
Instituto de Neurociencias San Agustín
La Plata, 1900, Argentina
Instituto Médico de la Fundación Estudios Clínicos
Rosario, S2000DEJ, Argentina
Centro de Investigacion y Asistencia en Psiquiatria (CIAP)
Rosario, S2000QJI, Argentina
Griffith Health
Southport, Queensland, 4125, Australia
Peninsula Therapeutic and Research Group
Frankston, Victoria, 3199, Australia
Albert Road Clinic
Melbourne, Victoria, 3004, Australia
Monash Alfred Psychiatry Research Centre
Melbourne, Victoria, 3004, Australia
Mental Health Center "Prof. Dr. Ivan Temkov - Burgas" EOOD
Burgas, 9001, Bulgaria
Filipopolis Ambulatory for Group Practice for Specialized Care in Psychiatry
Plovdiv, 4000, Bulgaria
Medical Center Intermedica Ltd.
Sofia, 1680, Bulgaria
University of Calgary
Calgary, Alberta, T2N 4Z6, Canada
OCT Research ULC
Kelowna, British Columbia, V1Y 1Z9, Canada
Braxia Scientific Corp. (CRTCE Mississauga)
Mississauga, Ontario, L5C 4E7, Canada
Centre for Addiction and Mental Health (CAMH)
Toronto, Ontario, M6J 1H4, Canada
Neuropsychiatry, s.r.o.
Hradec Králové, 500 09, Czechia
Clinical Research Foundation s.r.o
Kladno, 27201, Czechia
MP Meditrine s.r.o.
Ostrava, 708 00, Czechia
A-SHINE s.r.o
Pilsen, 31200, Czechia
Clintrial s.r.o.
Prague, 10000, Czechia
AD71 s.r.o.
Prague, 10900, Czechia
INEP medical s.r.o.
Prague, 18600, Czechia
HOP Dijon-Bourgogne
Dijon, 21079, France
CAB Médical Psyché
Douai, 59500, France
CAB Ambroise Paré
Élancourt, 78990, France
HOP la Colombière
Montpellier, 34295, France
HOP Saint-Jacques
Nantes, 44093, France
HOP Pasteur
Nice, 06000, France
HOP Carémeau
Nîmes, 30029, France
CTR Psychiatrique Universitaire
Saint-Cyr-sur-Loire, 37540, France
HOP Purpan
Toulouse, 31059, France
Zentrum für klinische Forschung Dr. med. I. Schöll GmbH
Bad Homburg, 61350, Germany
Universitätsklinikum Frankfurt
Frankfurt am Main, 60590, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55131, Germany
Zentralinstitut für seelische Gesundheit
Mannheim, 68159, Germany
Praxis für Psychiatrie und Psychotherapie
Stralsund, 18439, Germany
Studienzentrum Nord-West
Westerstede, 26655, Germany
Obuda Health Center
Budapest, 1036, Hungary
Semmelweis University
Budapest, 1083, Hungary
Bugat Pal Hospital, Gyongyos
Gyöngyös, 3200, Hungary
National Center for Global Health and Medicine Kohnodai Hospital
Chiba, Ichikawa, 272-8516, Japan
Kaku Mental Clinic
Fukuoka, Fukuoka, 810-0022, Japan
Fukuoka University Hospital
Fukuoka, Fukuoka, 814-0180, Japan
Kuramitsu Hospital
Fukuoka, Fukuoka, 819-0037, Japan
Hokudai-dori Mental Health Clinic
Hokkaido, Sapporo, 001-0010, Japan
Arai Clinic
Hyogo, Amagasaki, 660-0882, Japan
Tatsuta Clinic
Hyogo, Kobe, 651-0097, Japan
Kishiro Mental Clinic
Kanagawa, Kawasaki, 214-0014, Japan
Yutaka Clinic
Kanagawa,Sagamihara, 252-0303, Japan
Yuge Neuropsychiatric Hospital
Kumamoto, Kumamoto, 861-8002, Japan
Arata Clinic
Nagasaki, Nagasaki, 852-8154, Japan
Nara Medical University Hospital
Nara, Kashihara, 634-8522, Japan
Rainbow and Sea Hospital
Saga, Karatsu, 847-0031, Japan
Inuo Hospital
Saga, Tosu, 841-0081, Japan
National Center of Neurology and Psychiatry
Tokyo, Kodaira, 187-8851, Japan
Tamachi mita cocoromi Clinic
Tokyo, Minato-ku, 108-0023, Japan
Sancha Mental Clinic
Tokyo, Setagaya-ku, 154-0004, Japan
Maynds Tower Mental Clinic
Tokyo, Shibuya-ku, 151-0053, Japan
Ichigaya Himorogi Clinic
Tokyo, Shinjuku-ku, 162-0843, Japan
Ohwa Mental Clinic
Tokyo, Toshima-ku, 170-0002, Japan
Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk
Gdansk, 80-382, Poland
Synexus Lodz Medical Center
Lodz, 90127, Poland
Specialist Psychiatric Healthcare Centre in Lodz
Lodz, 91-229, Poland
Clinical Best Solutions
Lublin, 20-078, Poland
Centrum Medyczne "Luxmed" Sp. z o.o.
Lublin, 20-109, Poland
Synexus Poland, Branch in Poznan
Poznan, 60-702, Poland
Federal State Budget Institution "Mental Health Research Center"
Moscow, 115522, Russia
SBI of HC "Z. P. Solovyov Scientific&pract psychoneurolog.Cent"
Moscow, 129110, Russia
SBHI "Psychiatric Hospital #1 P.P.Kashchenko"
Saint Petersburg, 190121, Russia
FSBI Bekhterev Net.Med.Res.Cen.of Psych&Neuro
Saint Petersburg, 192019, Russia
LLC "MK-Med"
Saint Petersburg, 197373, Russia
SHI "Reg.Clin.Psychiatric Hosp.of Saint Sophia"
Saratov, 410060, Russia
FSBEI of HE Smolensk State Medical University
Smolensk, 214019, Russia
MUDr. Beata Dupejová
Banská Bystrica, 974 04, Slovakia
J & J SMART, s.r.o., psychiatric clinic
Bratislava, 81107, Slovakia
MENTUM s.r.o.
Bratislava, 82007, Slovakia
EPAMED s.r.o.
Košice, 040 01, Slovakia
Psychiatricka klinika I.UN L. Pasteura
Košice, 4001, Slovakia
CENTRUM ZDRAVIA R.B.K, s.r.o., psychiatric clinic
Svidník, 089 01, Slovakia
Pro mente sana s.r.o., Psychiatric clinic
Trenčín, 911 01, Slovakia
Crystal Comfort s.r.o
Vranov nad Topľou, 093 01, Slovakia
Hospital Universitario Fundación Alcorcón
Alcorcón, 28922, Spain
Hestia Palau
Barcelona, 08025, Spain
Hospital Clínic de Barcelona
Barcelona, 08036, Spain
Hospital Jerez de la Frontera
Jerez de la Frontera, 11407, Spain
Hospital Ramón y Cajal
Madrid, 28034, Spain
Centro de Salud de San Juan
Salamanca, 37005, Spain
Related Publications (1)
Shelton RC, Pizzagalli DA, Cohen EA, Hori H, Dickschat U, Asafu-Adjei J, Feldbarg A, Just S, Roehrle M, Sommer S, Sussmuth SD. Efficacy, Tolerability, and Safety of TRPC4/5 Inhibitor BI 1358894 in Patients With Major Depressive Disorder and Inadequate Response to Antidepressants: A Phase 2 Randomized, Placebo-Controlled, Parallel Group, Dose-Ranging Trial. J Clin Psychiatry. 2025 Sep 3;86(3):25m15868. doi: 10.4088/JCP.25m15868.
PMID: 40900110DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boehringer Ingelheim, Call Center
- Organization
- Boehringer Ingelheim
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 18, 2020
First Posted
August 20, 2020
Study Start
November 20, 2020
Primary Completion
January 10, 2024
Study Completion
February 2, 2024
Last Updated
March 6, 2025
Results First Posted
March 6, 2025
Record last verified: 2025-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- 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.
- 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'.
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.