A Study to Test the Effect of Different Doses of BI 13588... | NCT04521478 | Trialant
NCT04521478
Sponsor
Boehringer Ingelheim
Status
Completed
Last Update Posted
Mar 6, 2025Actual
Enrollment
389Actual
Phase
Phase 2
Conditions
Depressive Disorder, Major
Interventions
BI 1358894
Placebo
Quetiapine
Countries
United States
Argentina
Australia
Bulgaria
Canada
Czechia
France
Germany
Hungary
Japan
Poland
Russia
Slovakia
Spain
Protocol Section
Identification Module
NCT ID
NCT04521478
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
1402-0011
Secondary IDs
ID
Type
Description
Link
2019-004264-21
EudraCT Number
Brief Title
A Study to Test the Effect of Different Doses of BI 1358894 and Quetiapine in People With Depression
Official Title
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.
Acronym
Not provided
Organization
Boehringer IngelheimINDUSTRY
Status Module
Record Verification Date
Feb 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Nov 20, 2020Actual
Primary Completion Date
Jan 10, 2024Actual
Completion Date
Feb 2, 2024Actual
First Submitted Date
Aug 18, 2020
First Submission Date that Met QC Criteria
Aug 19, 2020
First Posted Date
Aug 20, 2020Actual
Results Waived
Not provided
Results First Submitted Date
Jan 13, 2025
Results First Submitted that Met QC Criteria
Feb 17, 2025
Results First Posted Date
Mar 6, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Feb 17, 2025
Last Update Posted Date
Mar 6, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Boehringer IngelheimINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Detailed Description
Not provided
Conditions Module
Conditions
Depressive Disorder, Major
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
389Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
5 mg BI 1358894
Experimental
Participants 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.
Drug: BI 1358894
Placebo
Placebo Comparator
Participants 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).
Drug: Placebo
Quetiapine
Active Comparator
Participants 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.
Drug: Quetiapine
25 mg BI 1358894
Interventions
Name
Type
Description
Arm Group Labels
Other Names
BI 1358894
Drug
BI 1358894
125 mg BI 1358894
25 mg BI 1358894
5 mg BI 1358894
75 mg BI 1358894
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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
Measure
Description
Time Frame
Number of Participants With Response Defined as ≥ 50% Montgomery-Åsberg Depression Rating Scale (MADRS) Reduction From Baseline at Week 6
Number of participants with response defined as ≥ 50% MADRS reduction from baseline at Week 6 is reported. Percent reduction from baseline was calculated as follows: [(MADRS total score at baseline - MADRS total score at week 6)/ MADRS total score at baseline] *100.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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)
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.
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.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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'.
All patients were screened for eligibility prior to participation in the trial, to ensure that they met all inclusion and none of the exclusion criteria.
One patient was randomized to the placebo arm but treated with 125 mg BI 1358894.
Recruitment Details
This was a Phase II, 6-week parallel-group multicenter, randomized, double blind, doubledummy, placebo-controlled trial with a Quetiapine arm in participants with Major Depressive Disorder (MDD) with inadequate response to ongoing treatment with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin Norepinephrine Reuptake Inhibitor (SNRI) or bupropion.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo
Participants 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).
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jun 7, 2023
Dec 18, 2024
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Experimental
Participants 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.
Drug: BI 1358894
75 mg BI 1358894
Experimental
Participants 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.
Drug: BI 1358894
125 mg BI 1358894
Experimental
Participants 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.
Drug: BI 1358894
Placebo
Drug
Placebo
Placebo
Quetiapine
Drug
quetiapine
Quetiapine
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
Change from baseline in STAI State and Trait version scores at Week 6 is reported. The STAI comprises separate self-report scales for measuring state and trait anxiety. Both consist of 20 statements. The S-Anxiety scale evaluates how respondents feel "right now, at this moment." The T-Anxiety scale assesses how people generally feel. Each STAI item is given a weighted score of 1 to 4. Scores for both scales can vary from 20 (minimum) to 80 (maximum). Higher scores indicate greater anxiety.
Least squares mean and adjusted standard error were estimated by REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline 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.
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 6
Change from baseline in CGI-S score at Week 6 is reported. The CGI-S rating scale 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.
Least squares mean and adjusted standard error were estimated by REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6
Change from baseline in SMDDS total score at Week 6 is reported. The SMDDS is a 16-item, patient-reported outcome measure developed to capture the core symptoms of MDD. 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.
Least squares mean and adjusted standard error were estimated by REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
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
FG001
5 mg BI 1358894
Participants 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.
FG002
25 mg BI 1358894
Participants 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.
FG003
75 mg BI 1358894
Participants 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.
FG004
125 mg BI 1358894
Participants 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.
FG005
Quetiapine
Participants 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.
FG000129 subjects
FG00136 subjects
FG00239 subjects
FG00339 subjects
FG00474 subjects
FG00572 subjects
Treated
one participant from the "Placebo" arm was treated with 125 mg BI 1358894, and thus was analyzed as part of the "125 mg BI 1358894" arm for the Safety Analyses. This patient is shown here in the "Placebo" arm.
FG000129 subjects
FG00136 subjects
FG00239 subjects
FG00339 subjects
FG00474 subjects
FG00571 subjects
COMPLETED
FG000116 subjects
FG00131 subjects
FG00233 subjects
FG00334 subjects
FG00467 subjects
FG00559 subjects
NOT COMPLETED
FG00013 subjects
FG0015 subjects
FG0026 subjects
FG0035 subjects
FG0047 subjects
FG00513 subjects
Type
Comment
Reasons
Protocol Violation
FG0002 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Technical Problems
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Burden of Study Procedures
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Lack of Efficacy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Adverse Event
FG0007 subjects
FG0010 subjects
FG0022 subjects
FG0031 subjects
FG004
No Reason Available
FG0000 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
FG004
Other than listed
FG0003 subjects
FG0013 subjects
FG0023 subjects
FG0032 subjects
FG004
Not treated
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Treated Set (TS): all participants that have been randomized and that received at least one administration of study drug. Participants are analysed according to the actual received treatment.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo
Participants 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).
BG001
5 mg BI 1358894
Participants 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.
BG002
25 mg BI 1358894
Participants 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.
BG003
75 mg BI 1358894
Participants 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.
BG004
125 mg BI 1358894
Participants 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.
BG005
Quetiapine
Participants 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.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000128
BG00136
BG00239
BG00339
BG00475
BG00571
BG006388
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00042.9± 13.0
BG00139.7± 13.8
BG00244.7± 12.1
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00082
BG00127
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG00019
BG0015
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Montgomery-Åsberg Depression Rating Scale (MADRS) total score
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).
Baseline MADRS total score is the last non-missing value recorded prior to first dose of trial medication.
Mean
Standard Deviation
Score on a scale
Title
Denominators
Categories
Title
Measurements
BG00032.0± 6.4
BG001
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
Primary
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.
Full analysis set (FAS): all participants in TS that have a baseline and at least one evaluable post-baseline measurement. As per protocol, data from participants assigned to the quetiapine arm were not included in the primary endpoint.
Posted
Least Squares Mean
Standard Error
Units on a scale
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.
ID
Title
Description
OG000
Placebo
Participants 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).
OG001
5 mg BI 1358894
Participants 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.
OG002
25 mg BI 1358894
Participants 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.
OG003
75 mg BI 1358894
Participants 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.
OG004
125 mg BI 1358894
Participants 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.
Units
Counts
Participants
OG000126
OG00136
OG00239
OG003
Title
Denominators
Categories
Title
Measurements
OG000-13.0± 1.0
OG001-12.4± 2.0
OG002-10.8± 1.9
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Adjusted means and confidence intervals were estimated using REML-based 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.
Mixed Models Analysis
0.7636
Mean Difference (Net)
0.7
Standard Error of the Mean
2.2
2-Sided
90
-3.0
4.3
Difference = (adjusted mean 5 mg BI 1358894) - (adjusted mean Placebo)
Secondary
Number of Participants With Response Defined as ≥ 50% Montgomery-Åsberg Depression Rating Scale (MADRS) Reduction From Baseline at Week 6
Number of participants with response defined as ≥ 50% MADRS reduction from baseline at Week 6 is reported. Percent reduction from baseline was calculated as follows: [(MADRS total score at baseline - MADRS total score at week 6)/ MADRS total score at baseline] *100.
Full analysis set (FAS): all participants in TS that have a baseline and at least one evaluable post-baseline measurement. As per protocol, data from participants assigned to the quetiapine arm were not included in the secondary endpoints.
Posted
Count of Participants
Participants
Prior to the first intake of the trial medication (week 0, baseline) and after 6 weeks of treatment.
ID
Title
Description
OG000
Placebo
Participants 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).
OG001
5 mg BI 1358894
Participants 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.
Secondary
Change From Baseline in State-Trait Anxiety Inventory (STAI) State and Trait Version Scores at Week 6
Change from baseline in STAI State and Trait version scores at Week 6 is reported. The STAI comprises separate self-report scales for measuring state and trait anxiety. Both consist of 20 statements. The S-Anxiety scale evaluates how respondents feel "right now, at this moment." The T-Anxiety scale assesses how people generally feel. Each STAI item is given a weighted score of 1 to 4. Scores for both scales can vary from 20 (minimum) to 80 (maximum). Higher scores indicate greater anxiety.
Least squares mean and adjusted standard error were estimated by REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline 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.
Full analysis set (FAS): all participants in TS that have a baseline and at least one evaluable post-baseline measurement. As per protocol, data from participants assigned to the quetiapine arm were not included in the secondary endpoints.
Posted
Least Squares Mean
Standard Error
Units on a scale
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.
ID
Title
Description
OG000
Placebo
Participants 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).
Secondary
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 6
Change from baseline in CGI-S score at Week 6 is reported. The CGI-S rating scale 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.
Least squares mean and adjusted standard error were estimated by REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Full analysis set (FAS): all participants in TS that have a baseline and at least one evaluable post-baseline measurement. As per protocol, data from participants assigned to the quetiapine arm were not included in the secondary endpoints.
Posted
Least Squares Mean
Standard Error
Units on a scale
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.
ID
Title
Description
OG000
Placebo
Participants 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).
Secondary
Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6
Change from baseline in SMDDS total score at Week 6 is reported. The SMDDS is a 16-item, patient-reported outcome measure developed to capture the core symptoms of MDD. 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.
Least squares mean and adjusted standard error were estimated by REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Full analysis set (FAS): all participants in TS that have a baseline and at least one evaluable post-baseline measurement. As per protocol, data from participants assigned to the quetiapine arm were not included in the secondary endpoints.
Posted
Least Squares Mean
Standard Error
Units on a scale
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.
ID
Title
Description
OG000
Placebo
Participants 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).
Time Frame
From first treatment administration until last treatment administration + 28 days, up to approximately 11 weeks.
Description
Treated Set (TS): all participants that have been randomized and that received at least one administration of study drug. Participants are analysed according to the actual received treatment.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo
Participants 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).
0
128
7
128
32
128
EG001
5 mg BI 1358894
Participants 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.
0
36
0
36
16
36
EG002
25 mg BI 1358894
Participants 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.
0
39
2
39
22
39
EG003
75 mg BI 1358894
Participants 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.
0
39
2
39
24
39
EG004
125 mg BI 1358894
Participants 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.
0
75
1
75
34
75
EG005
Quetiapine
Participants 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.
0
71
1
71
43
71
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Genital herpes
Infections and infestations
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0020 affected39 at risk
EG0031 affected39 at risk
EG0040 affected75 at risk
EG0050 affected71 at risk
Blood creatinine increased
Investigations
MedDRA 26.1
Systematic Assessment
EG0001 affected128 at risk
EG0010 affected36 at risk
EG0020 affected39 at risk
EG003
Myeloproliferative neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0020 affected39 at risk
EG003
Emotional distress
Psychiatric disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0021 affected39 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA 26.1
Systematic Assessment
EG0006 affected128 at risk
EG0010 affected36 at risk
EG0020 affected39 at risk
EG003
Pulmonary fibrosis
Respiratory, thoracic and mediastinal disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0021 affected39 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Vertigo
Ear and labyrinth disorders
MedDRA 26.1
Systematic Assessment
EG0001 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG0030 affected39 at risk
EG0043 affected75 at risk
EG0051 affected71 at risk
Abdominal pain
Gastrointestinal disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0020 affected39 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 26.1
Systematic Assessment
EG0004 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG003
Fatigue
General disorders
MedDRA 26.1
Systematic Assessment
EG0004 affected128 at risk
EG0015 affected36 at risk
EG0023 affected39 at risk
EG003
COVID-19
Infections and infestations
MedDRA 26.1
Systematic Assessment
EG0005 affected128 at risk
EG0011 affected36 at risk
EG0021 affected39 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 26.1
Systematic Assessment
EG0002 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0012 affected36 at risk
EG0020 affected39 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 26.1
Systematic Assessment
EG0002 affected128 at risk
EG0011 affected36 at risk
EG0022 affected39 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG003
Disturbance in attention
Nervous system disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 26.1
Systematic Assessment
EG0003 affected128 at risk
EG0012 affected36 at risk
EG0026 affected39 at risk
EG003
Headache
Nervous system disorders
MedDRA 26.1
Systematic Assessment
EG00013 affected128 at risk
EG0019 affected36 at risk
EG0024 affected39 at risk
EG003
Sedation
Nervous system disorders
MedDRA 26.1
Systematic Assessment
EG0001 affected128 at risk
EG0010 affected36 at risk
EG0021 affected39 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 26.1
Systematic Assessment
EG0004 affected128 at risk
EG0011 affected36 at risk
EG0021 affected39 at risk
EG003
Aggression
Psychiatric disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0012 affected36 at risk
EG0020 affected39 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 26.1
Systematic Assessment
EG0001 affected128 at risk
EG0012 affected36 at risk
EG0020 affected39 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 26.1
Systematic Assessment
EG0001 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA 26.1
Systematic Assessment
EG0002 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0011 affected36 at risk
EG0021 affected39 at risk
EG003
Hypertension
Vascular disorders
MedDRA 26.1
Systematic Assessment
EG0000 affected128 at risk
EG0010 affected36 at risk
EG0022 affected39 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
Adjusted means and confidence intervals were estimated using REML-based 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.
Mixed Models Analysis
0.3040
Mean Difference (Net)
2.3
Standard Error of the Mean
2.2
2-Sided
90
-1.4
5.9
Difference = (adjusted mean 25 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG003
Adjusted means and confidence intervals were estimated using REML-based 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.
Mixed Models Analysis
0.3090
Mean Difference (Net)
2.2
Standard Error of the Mean
2.2
2-Sided
90
-1.4
5.7
Difference = (adjusted mean 75 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG004
Adjusted means and confidence intervals were estimated using REML-based 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.
Mixed Models Analysis
0.3694
Mean Difference (Net)
1.5
Standard Error of the Mean
1.7
2-Sided
90
-1.3
4.4
Difference = (adjusted mean 125 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG001
OG002
OG003
OG004
The Multiple Comparison Procedures and Modeling (MCPMod) procedure used the estimated values from an MMRM model as input and allowed for simultaneous evaluation of different potential dose response patterns (Linear, Exponential, Emax1, Emax2, Sigmoid Emax), while protecting the overall false positive rate (probability of Type I error) using a one-sided, nominal α level of 10 %.
MCPMod Linear model
No parameter assumptions required. Corresponding dose response is linear
0.9158
Other
OG000
OG001
OG002
OG003
OG004
The Multiple Comparison Procedures and Modeling (MCPMod) procedure used the estimated values from an MMRM model as input and allowed for simultaneous evaluation of different potential dose response patterns (Linear, Exponential, Emax1, Emax2, Sigmoid Emax), while protecting the overall false positive rate (probability of Type I error) using a one-sided, nominal α level of 10 %.
MCPMod Exponential model
Assumption: 5% of the maximum effect is achieved at 25 mg; corresponding to a drug effect achieved mainly at higher doses
0.8676
Other
OG000
OG001
OG002
OG003
OG004
The Multiple Comparison Procedures and Modeling (MCPMod) procedure used the estimated values from an MMRM model as input and allowed for simultaneous evaluation of different potential dose response patterns (Linear, Exponential, Emax1, Emax2, Sigmoid Emax), while protecting the overall false positive rate (probability of Type I error) using a one-sided, nominal α level of 10 %.
MCPMod Emax1 model
Assumption: 50% of the maximum effect is achieved at 25 mg; corresponding to the assumed true median effective dose (ED50) = 25 mg
0.9552
Other
OG000
OG001
OG002
OG003
OG004
The Multiple Comparison Procedures and Modeling (MCPMod) procedure used the estimated values from an MMRM model as input and allowed for simultaneous evaluation of different potential dose response patterns (Linear, Exponential, Emax1, Emax2, Sigmoid Emax), while protecting the overall false positive rate (probability of Type I error) using a one-sided, nominal α level of 10 %.
MCPMod Emax2 model
Assumption: 70% of the maximum effect is achieved at 5 mg; corresponding to a drug effect achieved mainly with low doses, ED50 = 2.14 mg
0.9619
Other
OG000
OG001
OG002
OG003
OG004
The Multiple Comparison Procedures and Modeling (MCPMod) procedure used the estimated values from an MMRM model as input and allowed for simultaneous evaluation of different potential dose response patterns (Linear, Exponential, Emax1, Emax2, Sigmoid Emax), while protecting the overall false positive rate (probability of Type I error) using a one-sided, nominal α level of 10 %.
MCPMod Sigmoid Emax model
Assumption: 50% of the maximum effect is achieved at 25 mg, 90% 75 mg; corresponding to a more flexible model of the assumed true ED50 = 25 mg
0.9507
Other
OG002
25 mg BI 1358894
Participants 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.
OG003
75 mg BI 1358894
Participants 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.
OG004
125 mg BI 1358894
Participants 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.
Units
Counts
Participants
OG000126
OG00136
OG00239
OG00339
OG00472
Title
Denominators
Categories
Title
Measurements
OG00040
OG00110
OG0029
OG00312
OG00423
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Logistic regression model, including the fixed categorical effects of treatment and baseline MDD severity.
Regression, Logistic
0.8889
Odds Ratio (OR)
0.9427
2-Sided
90
0.4709
1.8873
5 mg BI 1358894 vs Placebo
Other
OG000
OG002
Logistic regression model, including the fixed categorical effects of treatment and baseline MDD severity.
Regression, Logistic
0.3284
Odds Ratio (OR)
0.6581
2-Sided
90
0.3255
1.3307
25 mg BI 1358894 vs Placebo
Other
OG000
OG003
Logistic regression model, including the fixed categorical effects of treatment and baseline MDD severity.
Regression, Logistic
0.8048
Odds Ratio (OR)
1.1026
2-Sided
90
0.5757
2.1114
75 mg BI 1358894 vs Placebo
Other
OG000
OG004
Logistic regression model, including the fixed categorical effects of treatment and baseline MDD severity.
Regression, Logistic
0.9820
Odds Ratio (OR)
1.0072
2-Sided
90
0.5968
1.6999
125 mg BI 1358894 vs Placebo
Other
OG001
5 mg BI 1358894
Participants 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.
OG002
25 mg BI 1358894
Participants 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.
OG003
75 mg BI 1358894
Participants 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.
OG004
125 mg BI 1358894
Participants 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.
Units
Counts
Participants
OG000126
OG00136
OG00239
OG00339
OG00472
Title
Denominators
Categories
S-Anxiety
Title
Measurements
OG000-11.3± 1.2
OG001-7.0± 2.3
OG002-8.9± 2.3
OG003-12.3± 2.2
OG004-8.6± 1.6
T-Anxiety
Title
Measurements
OG000-11.0± 1.1
OG001-6.9± 2.1
OG002-10.2± 2.1
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline score (S-Anxiety scale). 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.
Mixed Models Analysis
0.1013
Mean Difference (Net)
4.3
Standard Error of the Mean
2.6
2-Sided
90
0.0
8.6
Difference = (adjusted mean 5 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG002
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline score (S-Anxiety scale). 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.
Mixed Models Analysis
0.3596
Mean Difference (Net)
2.4
Standard Error of the Mean
2.6
2-Sided
90
-1.9
6.6
Difference = (adjusted mean 25 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG003
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline score (S-Anxiety scale). 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.
Mixed Models Analysis
0.6745
Mean Difference (Net)
-1.1
Standard Error of the Mean
2.5
2-Sided
90
-5.2
3.1
Difference = (adjusted mean 75 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG004
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline score (S-Anxiety scale). 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.
Mixed Models Analysis
0.1870
Mean Difference (Net)
2.7
Standard Error of the Mean
2.0
2-Sided
90
-0.7
6.0
Difference = (adjusted mean 125 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG001
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline score (T-Anxiety scale). 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.
Mixed Models Analysis
0.0921
Mean Difference (Net)
4.1
Standard Error of the Mean
2.4
2-Sided
90
0.1
8.1
Difference = (adjusted mean 5 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG002
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline score (T-Anxiety scale). 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.
Mixed Models Analysis
0.7395
Mean Difference (Net)
0.8
Standard Error of the Mean
2.4
2-Sided
90
-3.2
4.8
Difference = (adjusted mean 25 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG003
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline score (T-Anxiety scale). 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.
Mixed Models Analysis
0.6296
Mean Difference (Net)
1.1
Standard Error of the Mean
2.4
2-Sided
90
-2.7
5.0
Difference = (adjusted mean 75 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG004
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of baseline score (T-Anxiety scale). 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.
Mixed Models Analysis
0.0429
Mean Difference (Net)
3.8
Standard Error of the Mean
1.9
2-Sided
90
0.7
6.9
Difference = (adjusted mean 125 mg BI 1358894) - (adjusted mean Placebo)
Other
OG001
5 mg BI 1358894
Participants 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.
OG002
25 mg BI 1358894
Participants 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.
OG003
75 mg BI 1358894
Participants 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.
OG004
125 mg BI 1358894
Participants 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.
Units
Counts
Participants
OG000126
OG00136
OG00239
OG00339
OG00472
Title
Denominators
Categories
Title
Measurements
OG000-1.3± 0.1
OG001-1.2± 0.2
OG002-1.2± 0.2
OG003-1.1± 0.2
OG004-1.1± 0.2
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Mixed Models Analysis
0.6211
Mean Difference (Net)
0.1
Standard Error of the Mean
0.3
2-Sided
90
-0.3
0.5
Difference = (adjusted mean 5 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG002
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Mixed Models Analysis
0.5158
Mean Difference (Net)
0.2
Standard Error of the Mean
0.2
2-Sided
90
-0.2
0.6
Difference = (adjusted mean 25 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG003
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Mixed Models Analysis
0.4518
Mean Difference (Net)
0.2
Standard Error of the Mean
0.2
2-Sided
90
-0.2
0.6
Difference = (adjusted mean 75 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG004
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Mixed Models Analysis
0.2347
Mean Difference (Net)
0.2
Standard Error of the Mean
0.2
2-Sided
90
-0.1
0.6
Difference = (adjusted mean 125 mg BI 1358894) - (adjusted mean Placebo)
Other
OG001
5 mg BI 1358894
Participants 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.
OG002
25 mg BI 1358894
Participants 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.
OG003
75 mg BI 1358894
Participants 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.
OG004
125 mg BI 1358894
Participants 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.
Units
Counts
Participants
OG000126
OG00136
OG00239
OG00339
OG00472
Title
Denominators
Categories
Title
Measurements
OG000-13.3± 1.2
OG001-9.9± 2.2
OG002-8.9± 2.2
OG003-12.3± 2.1
OG004-10.5± 1.6
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Mixed Models Analysis
0.1723
Mean Difference (Net)
3.4
Standard Error of the Mean
2.5
2-Sided
90
-0.7
7.6
Difference = (adjusted mean 5 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG002
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Mixed Models Analysis
0.0757
Mean Difference (Net)
4.4
Standard Error of the Mean
2.5
2-Sided
90
0.3
8.5
Difference = (adjusted mean 25 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG003
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Mixed Models Analysis
0.6864
Mean Difference (Net)
1.0
Standard Error of the Mean
2.4
2-Sided
90
-3.0
5.0
Difference = (adjusted mean 75 mg BI 1358894) - (adjusted mean Placebo)
Other
OG000
OG004
Adjusted means and confidence intervals were estimated using REML-based MMRM including the fixed categorical effects of treatment, concomitant psychotherapy use (yes vs. no), and the fixed continuous effect of the baseline 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.
Mixed Models Analysis
0.1585
Mean Difference (Net)
2.8
Standard Error of the Mean
1.9
2-Sided
90
-0.5
6.0
Difference = (adjusted mean 125 mg BI 1358894) - (adjusted mean Placebo)