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.

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.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: Placebo; Drug: BI 1358894; Drug: Quetiapine

• Study Type: Interventional
• Enrollment (Actual): 389
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Boehringer Ingelheim; Phone Number: 1-800-243-0127; Email: clintriage.rdg@boehringer-ingelheim.com

Study Locations

• Argentina
  • Caba, Argentina, C1133AAH
    • Fundación para el Estudio y Tratamiento de las Enfermedades Mentales (FETEM)
  • Cordoba, Argentina, 5004
    • CEN (Centro Especializado Neurociencias)
  • Cordoba, Argentina, X5003DCE
    • Instituto DAMIC - Fundacion Rusculleda
  • La Plata, Argentina, 1900
    • Instituto de Neurociencias San Agustin
  • La Plata, Argentina, 1900
    • Clinica Privada de Salud Mental Santa Teresa de Ávila
  • La Plata, Argentina, 1900
    • CENPIA-Centro de Estudios Neuropsiquiátricos y Psicológicos Integral Ambulatorio
  • Rosario, Argentina, S2000DEJ
    • Instituto Medico de La Fundacion Estudios Clinicos
  • Rosario, Argentina, S2000QJI
    • Centro de Investigacion y Asistencia en Psiquiatria (CIAP)
• Australia
  • Queensland
    • Southport, Queensland, Australia, 4125
      • Griffith Health
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula Therapeutic and Research Group
    • Melbourne, Victoria, Australia, 3004
      • Monash Alfred Psychiatry Research Centre
    • Melbourne, Victoria, Australia, 3004
      • Albert Road Clinic
• Bulgaria
  • Burgas, Bulgaria, 9001
    • Mental Health Center "Prof. Dr. Ivan Temkov - Burgas" EOOD
  • Plovdiv, Bulgaria, 4000
    • "Filipopolis" - Ambulatory for Group Practice for Specialized Care in Psychiatry
  • Sofia, Bulgaria, 1680
    • Medical Center Intermedica Ltd.
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • OCT Research ULC
  • Ontario
    • Mississauga, Ontario, Canada, L5C 4E7
      • Braxia Scientific Corp. (CRTCE Mississauga)
    • Toronto, Ontario, Canada, M6J 1H4
      • Centre for Addiction and Mental Health (CAMH)
• Czechia
  • Hradec Kralove, Czechia, 500 09
    • Neuropsychiatry, s.r.o.
  • Kladno, Czechia, 27201
    • Clinical Research Foundation s.r.o
  • Ostrava-Poruba, Czechia, 708 68
    • MPMeditrine s.r.o.
  • Plzen, Czechia, 31200
    • A-SHINE s.r.o
  • Prague, Czechia, 10000
    • Clintrial s.r.o.
  • Prague, Czechia, 18600
    • INEP medical s.r.o.
  • Prague, Czechia, 10900
    • AD71 s.r.o.
• France
  • Dijon, France, 21079
    • HOP Dijon-Bourgogne
  • Douai, France, 59500
    • CAB Médical Psyché
  • Elancourt, France, 78990
    • CAB Ambroise Paré
  • Montpellier, France, 34295
    • HOP la Colombière
  • Nantes, France, 44093
    • HOP Saint-Jacques
  • Nice, France, 06000
    • HOP Pasteur
  • Nîmes, France, 30029
    • HOP Carémeau
  • Saint-Cyr-sur-Loire, France, 37540
    • CTR Psychiatrique Universitaire
  • Toulouse, France, 31059
    • HOP Purpan
• Germany
  • Bad Homburg, Germany, 61350
    • Zentrum für klinische Forschung Dr. med. I. Schöll
  • Frankfurt am Main, Germany, 60590
    • Universitatsklinikum Frankfurt
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Mannheim, Germany, 68159
    • Zentralinstitut für seelische Gesundheit
  • Stralsund, Germany, 18439
    • Praxis für Psychiatrie und Psychotherapie
  • Westerstede, Germany, 26655
    • Studienzentrum Nord-West
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis University
  • Budapest, Hungary, 1036
    • Obuda Health Center
  • Gyongyos, Hungary, 3200
    • Bugat Pal Hospital, Gyongyos
• Japan
  • Chiba, Ichikawa, Japan, 272-8516
    • National Center for Global Health and Medicine Kohnodai Hospital
  • Fukuoka, Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Fukuoka, Fukuoka, Japan, 819-0037
    • Kuramitsu Hospital
  • Fukuoka, Fukuoka, Japan, 810-0022
    • Kaku Mental Clinic
  • Hokkaido, Sapporo, Japan, 001-0010
    • Hokudai-dori Mental Health Clinic
  • Hyogo, Amagasaki, Japan, 660-0882
    • Arai Clinic
  • Hyogo, Kobe, Japan, 651-0097
    • Tatsuta Clinic
  • Kanagawa, Kawasaki, Japan, 214-0014
    • Kishiro Mental Clinic
  • Kanagawa,Sagamihara, Japan, 252-0303
    • Yutaka Clinic
  • Kumamoto, Kumamoto, Japan, 861-8002
    • Yuge Neuropsychiatric Hospital
  • Nagasaki, Nagasaki, Japan, 852-8154
    • Arata Clinic
  • Nara, Kashihara, Japan, 634-8522
    • Nara Medical University Hospital
  • Saga, Karatsu, Japan, 847-0031
    • Rainbow and Sea Hospital
  • Saga, Tosu, Japan, 841-0081
    • Inuo Hospital
  • Tokyo, Kodaira, Japan, 187-8851
    • National Center of Neurology and Psychiatry
  • Tokyo, Minato-ku, Japan, 108-0023
    • Tamachi mita cocoromi Clinic
  • Tokyo, Setagaya-ku, Japan, 154-0004
    • Sancha Mental Clinic
  • Tokyo, Shibuya-ku, Japan, 151-0053
    • Maynds Tower Mental Clinic
  • Tokyo, Shinjuku-ku, Japan, 162-0843
    • Ichigaya Himorogi Clinic
  • Tokyo, Toshima-ku, Japan, 170-0002
    • Ohwa Mental Clinic
• Poland
  • Gdansk, Poland, 80-382
    • Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk
  • Lodz, Poland, 90127
    • Synexus Lodz Medical Center
  • Lodz, Poland, 91-229
    • Specialist Psychiatric Healthcare Centre in Lodz
  • Lublin, Poland, 20-078
    • Clinical Best Solutions
  • Lublin, Poland, 20-109
    • Centrum Medyczne "Luxmed" Sp. z o.o.
  • Poznan, Poland, 60-702
    • Synexus Poland, Branch in Poznan
• Russian Federation
  • Moscow, Russian Federation, 115522
    • Federal State Budget Institution "Mental Health Research Center"
  • Moscow, Russian Federation, 129110
    • SBI of HC "Z. P. Solovyov Scientific&pract psychoneurolog.Cent"
  • Saratov, Russian Federation, 410060
    • SHI "Reg.Clin.Psychiatric Hosp.of Saint Sophia"
  • Smolensk, Russian Federation, 214019
    • FSBEI of HE Smolensk State Medical University
  • St. Petersburg, Russian Federation, 190121
    • SBHI "Psychiatric Hospital #1 P.P.Kashchenko"
  • St. Petersburg, Russian Federation, 192019
    • FSBI Bekhterev Net.Med.Res.Cen.of Psych&Neuro
  • St. Petersburg, Russian Federation, 197373
    • LLC "MK-Med"
• Slovakia
  • Banska Bystrica, Slovakia, 974 04
    • MUDr. Beata Dupejová
  • Bratislava, Slovakia, 81107
    • J & J SMART, s.r.o., psychiatric clinic
  • Bratislava, Slovakia, 82007
    • MENTUM s.r.o.
  • Kosice, Slovakia, 040 01
    • EPAMED s.r.o.
  • Kosice, Slovakia, 4001
    • Psychiatricka klinika I.UN L. Pasteura
  • Svidnik, Slovakia, 089 01
    • CENTRUM ZDRAVIA R.B.K, s.r.o., psychiatric clinic
  • Trencin, Slovakia, 911 01
    • Pro mente sana s.r.o., Psychiatric clinic
  • Vranov nad Toplou, Slovakia, 093 01
    • Crystal Comfort s.r.o
• Spain
  • Alcorcón, Spain, 28922
    • Hospital Universitario Fundación Alcorcón
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08025
    • Hestia Palau
  • Jerez de la Frontera, Spain, 11407
    • Hospital Jerez de la Frontera
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Salamanca, Spain, 37005
    • Centro de Salud de San Juan
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, LLC (CNS)
    • Long Beach, California, United States, 90807
      • Alliance Research
    • Sherman Oaks, California, United States, 91403
      • Schuster Medical Research Institute
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research
    • Sherman Oaks, California, United States, 91403
      • ASCLEPES Research Centers
    • Temecula, California, United States, 92591
      • Viking Clinical Research, Ltd.
    • Torrance, California, United States, 90504
      • Collaborative Neuroscience Research, LLC
  • Colorado
    • Denver, Colorado, United States, 80202
      • Mountain Mind. LLC
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • CT Clinical Research
    • Hartford, Connecticut, United States, 06106
      • Institute of Living
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Gulf Coast Clinical Research Center
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc
    • Miami, Florida, United States, 33135
      • Optimus U Corporation
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center
    • Atlanta, Georgia, United States, 30318
      • Advanced Discovery Research LLC
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Chicago Research Center, Incorporated
  • Kansas
    • Wichita, Kansas, United States, 67214
      • University of Kansas School of Medicine-Wichita
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Missouri
    • O'Fallon, Missouri, United States, 63368
      • Psychiatric Care and Research Center
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center for Emotional Fitness
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute
  • New York
    • New York, New York, United States, 10017
      • Synexus Clinical Research US, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Moosic, Pennsylvania, United States, 18507
      • Global Medical Institutes, LLC, Scranton Medical Institute
  • Washington
    • Everett, Washington, United States, 98201
      • Core Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

--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

Exclusion Criteria:

• 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 of any other mental disorder (in addition to those as described in Exclusion Criterion #1) that was the primary focus of treatment within 6 months prior to screening or at baseline (as per clinical discretion of the investigator)
• 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
• History of more than 2 unsuccessful monotherapy treatments (at adequate dosage and duration, per local prescribing information of the product) with an approved antidepressant medication for the current ongoing major depressive episode. These include ongoing monotherapy treatment with bupropion or a protocol specified SSRI or SNRI as described in Inclusion Criterion #3
• 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group 1; BI 1358894	Drug: BI 1358894; BI 1358894
Placebo Comparator: Placebo group; Placebo	Drug: Placebo; Placebo
Experimental: Treatment group 2; Quetiapine	Drug: Quetiapine; quetiapine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score	The MADRS consists of 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thought, suicidal thoughts. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression).	At week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response defined as ≥ 50% MADRS reduction from baseline		At week 6
Change from baseline in State-Trait Anxiety Inventory (STAI) State and Trait version scores	The S-Anxiety scale (STAI Form Y-1) consists of twenty statements that evaluate how respondents feel "right now, at this moment." The T-Anxiety scale (STAI Form Y-2) consists of twenty statements that assess how people generally feel. Each STAI item is given a weighted score of 1 to 4. A rating of 4 indicates the presence of a high level of anxiety for ten S-Anxiety items and eleven T-Anxiety items (e.g., "I feel frightened," "I feel upset"). A high rating indicates the absence of anxiety for the remaining ten S-Anxiety items and nine T-Anxiety items (e.g., "I feel calm," "I feel relaxed").Scores for both the S-Anxiety and the T-Anxiety scales can vary from a minimum of 20 to a maximum of 80. Higher scores indicate greater anxiety.	At week 6
Change from baseline in Clinical Global Impression Severity Scale (CGI-S) score	The CGI-S evaluates the severity of psychopathology on a scale of 1 to 7. Considering total clinical experience with the depression population, a participant is assessed on severity of illness at the time of rating according to: 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 participants. Higher scores indicate worsening.	At week 6
Change from baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) total score	The different categories and associated 16 items are: Negative Emotions/Mood: sadness, hopeless/helpless, irritability, anhedonia; Anxiety: feeling overwhelmed, worry; Low Energy: tiredness; Cognition: intrusive thoughts, poor concentration; Sleep Disturbances: general sleep adequacy; Self Harm/Suicide: life not worth living; Low Motivation: lack of drive, no interest in activities; Sense of Self: self-blame; Eating Behavior: poor appetite, overeating. The SMDDS uses a recall of "over the past 7 days" and participants respond to each question using a rating scale between 0 ("Not at all" or "Never") to 4 ("Extremely" or "Always"). The total score ranges from 0 to 60 with a higher score indicating more severe depressive symptomatology.	At week 6

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2020
• Primary Completion (Actual): January 10, 2024
• Study Completion (Actual): February 2, 2024

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 19, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Quetiapine Fumarate
• Other Study ID Numbers: 1402-0011; 2019-004264-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No