A Study to Test the Effect of Different Doses of BI 1358894 and Quetiapine in People With Depression

Depressive Disorder, Major Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04521478
• Other study ID #: 1402-0011
• Secondary ID: 2019-004264-21
• Status: Completed
• Phase: Phase 2
• Start date: November 20, 2020
• Est. completion date: February 2, 2024

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 389
• Est. completion date: February 2, 2024
• Est. primary completion date: January 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• BI 1358894
BI 1358894
• Placebo
Placebo
• Quetiapine
quetiapine

Locations

Country	Name	City	State
Argentina	Fundación para el Estudio y Tratamiento de las Enfermedades Mentales (FETEM)	Caba
Argentina	CEN (Centro Especializado Neurociencias)	Cordoba
Argentina	Instituto DAMIC - Fundacion Rusculleda	Cordoba
Argentina	CENPIA-Centro de Estudios Neuropsiquiátricos y Psicológicos Integral Ambulatorio	La Plata
Argentina	Clinica Privada de Salud Mental Santa Teresa de Avila	La Plata
Argentina	Instituto de Neurociencias San Agustín	La Plata
Argentina	Centro de Investigacion y Asistencia en Psiquiatria (CIAP)	Rosario
Argentina	Instituto Médico de la Fundación Estudios Clínicos	Rosario
Australia	Peninsula Therapeutic and Research Group	Frankston	Victoria
Australia	Albert Road Clinic	Melbourne	Victoria
Australia	Monash Alfred Psychiatry Research Centre	Melbourne	Victoria
Australia	Griffith Health	Southport	Queensland
Bulgaria	Mental Health Center "Prof. Dr. Ivan Temkov - Burgas" EOOD	Burgas
Bulgaria	"Filipopolis" - Ambulatory for Group Practice for Specialized Care in Psychiatry	Plovdiv
Bulgaria	Medical Center Intermedica Ltd.	Sofia
Canada	University of Calgary	Calgary	Alberta
Canada	OCT Research ULC	Kelowna	British Columbia
Canada	Braxia Scientific Corp. (CRTCE Mississauga)	Mississauga	Ontario
Canada	Centre for Addiction and Mental Health (CAMH)	Toronto	Ontario
Czechia	Neuropsychiatry, s.r.o.	Hradec Kralove
Czechia	Clinical Research Foundation s.r.o	Kladno
Czechia	MPMeditrine s.r.o.	Ostrava-Poruba
Czechia	A-SHINE s.r.o	Plzen
Czechia	AD71 s.r.o.	Prague
Czechia	Clintrial s.r.o.	Prague
Czechia	INEP medical s.r.o.	Prague
France	HOP Dijon-Bourgogne	Dijon
France	CAB Médical Psyché	Douai
France	CAB Ambroise Paré	Elancourt
France	HOP la Colombière	Montpellier
France	HOP Saint-Jacques	Nantes
France	HOP Pasteur	Nice
France	HOP Carémeau	Nîmes
France	CTR Psychiatrique Universitaire	Saint-Cyr-sur-Loire
France	HOP Purpan	Toulouse
Germany	Zentrum für klinische Forschung Dr. med. I. Schöll	Bad Homburg
Germany	Universitätsklinikum Frankfurt	Frankfurt am Main
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Zentralinstitut für seelische Gesundheit	Mannheim
Germany	Praxis für Psychiatrie und Psychotherapie	Stralsund
Germany	Studienzentrum Nord-West	Westerstede
Hungary	Obuda Health Center	Budapest
Hungary	Semmelweis University	Budapest
Hungary	Bugat Pal Hospital, Gyongyos	Gyongyos
Japan	National Center for Global Health and Medicine Kohnodai Hospital	Chiba, Ichikawa
Japan	Fukuoka University Hospital	Fukuoka, Fukuoka
Japan	Kaku Mental Clinic	Fukuoka, Fukuoka
Japan	Kuramitsu Hospital	Fukuoka, Fukuoka
Japan	Hokudai-dori Mental Health Clinic	Hokkaido, Sapporo
Japan	Arai Clinic	Hyogo, Amagasaki
Japan	Tatsuta Clinic	Hyogo, Kobe
Japan	Kishiro Mental Clinic	Kanagawa, Kawasaki
Japan	Yutaka Clinic	Kanagawa,Sagamihara
Japan	Yuge Neuropsychiatric Hospital	Kumamoto, Kumamoto
Japan	Arata Clinic	Nagasaki, Nagasaki
Japan	Nara Medical University Hospital	Nara, Kashihara
Japan	Rainbow and Sea Hospital	Saga, Karatsu
Japan	Inuo Hospital	Saga, Tosu
Japan	National Center of Neurology and Psychiatry	Tokyo, Kodaira
Japan	Tamachi mita cocoromi Clinic	Tokyo, Minato-ku
Japan	Sancha Mental Clinic	Tokyo, Setagaya-ku
Japan	Maynds Tower Mental Clinic	Tokyo, Shibuya-ku
Japan	Ichigaya Himorogi Clinic	Tokyo, Shinjuku-ku
Japan	Ohwa Mental Clinic	Tokyo, Toshima-ku
Poland	Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk	Gdansk
Poland	Specialist Psychiatric Healthcare Centre in Lodz	Lodz
Poland	Synexus Lodz Medical Center	Lodz
Poland	Centrum Medyczne "Luxmed" Sp. z o.o.	Lublin
Poland	Clinical Best Solutions	Lublin
Poland	Synexus Poland, Branch in Poznan	Poznan
Russian Federation	Federal State Budget Institution "Mental Health Research Center"	Moscow
Russian Federation	SBI of HC "Z. P. Solovyov Scientific&pract psychoneurolog.Cent"	Moscow
Russian Federation	SHI "Reg.Clin.Psychiatric Hosp.of Saint Sophia"	Saratov
Russian Federation	FSBEI of HE Smolensk State Medical University	Smolensk
Russian Federation	FSBI Bekhterev Net.Med.Res.Cen.of Psych&Neuro	St. Petersburg
Russian Federation	LLC "MK-Med"	St. Petersburg
Russian Federation	SBHI "Psychiatric Hospital #1 P.P.Kashchenko"	St. Petersburg
Slovakia	MUDr. Beata Dupejová	Banska Bystrica
Slovakia	J & J SMART, s.r.o., psychiatric clinic	Bratislava
Slovakia	MENTUM s.r.o.	Bratislava
Slovakia	EPAMED s.r.o.	Kosice
Slovakia	Psychiatricka klinika I.UN L. Pasteura	Kosice
Slovakia	CENTRUM ZDRAVIA R.B.K, s.r.o., psychiatric clinic	Svidnik
Slovakia	Pro mente sana s.r.o., Psychiatric clinic	Trencin
Slovakia	Crystal Comfort s.r.o	Vranov nad Toplou
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón
Spain	Hestia Palau	Barcelona
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Jerez de la Frontera	Jerez de la Frontera
Spain	Hospital Ramón y Cajal	Madrid
Spain	Centro de Salud de San Juan	Salamanca
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	Advanced Discovery Research LLC	Atlanta	Georgia
United States	Atlanta Center	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Center For Emotional Fitness	Cherry Hill	New Jersey
United States	Chicago Research Center, Incorporated	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	CT Clinical Research	Cromwell	Connecticut
United States	Mountain Mind. LLC	Denver	Colorado
United States	Core Clinical Research	Everett	Washington
United States	Precise Research Centers	Flowood	Mississippi
United States	Gulf Coast Clinical Research Center	Fort Myers	Florida
United States	Sarkis Clinical Trials	Gainesville	Florida
United States	Collaborative Neuroscience Network, LLC (CNS)	Garden Grove	California
United States	Institute of Living	Hartford	Connecticut
United States	Clinical Neuroscience Solutions, Inc	Jacksonville	Florida
United States	Alliance Research	Long Beach	California
United States	Hassman Research Institute	Marlton	New Jersey
United States	Optimus U Corporation	Miami	Florida
United States	Global Medical Institutes, LLC, Scranton Medical Institute	Moosic	Pennsylvania
United States	Synexus Clinical Research US, Inc.	New York	New York
United States	Psychiatric Care and Research Center	O'Fallon	Missouri
United States	Asclepes Research Centers	Sherman Oaks	California
United States	California Neuroscience Research	Sherman Oaks	California
United States	Schuster Medical Research Institute	Sherman Oaks	California
United States	Viking Clinical Research, Ltd.	Temecula	California
United States	Collaborative Neuroscience Research, LLC	Torrance	California
United States	University of Kansas School of Medicine-Wichita	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Hungary,  Japan,  Poland,  Russian Federation,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Response defined as = 50% MADRS reduction from baseline		At week 6
Secondary	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
Secondary	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
Secondary	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

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