Clinical trial NCT04521478: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2020-08-20
Enrollment: 389
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6
timeFrame: 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: Number of Participants With Response Defined as ≥ 50% Montgomery-Åsberg Depression Rating Scale (MADRS) Reduction From Baseline at Week 6
timeFrame: Prior to the first intake of the trial medication (week 0, baseline) and after 6 weeks of treatment.
measure: Change From Baseline in State-Trait Anxiety Inventory (STAI) State and Trait Version Scores at Week 6
timeFrame: 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.
measure: Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 6
timeFrame: 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.
measure: Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Week 6
timeFrame: 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.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC (CNS)
state: California
city: Long Beach
country: United States
facility: Alliance Research
state: California
city: Sherman Oaks
country: United States
facility: Asclepes Research Centers
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research
state: California
city: Sherman Oaks
country: United States
facility: Schuster Medical Research Institute
state: California
city: Temecula
country: United States
facility: Viking Clinical Research, Ltd.
state: California
city: Torrance
country: United States
facility: Collaborative Neuroscience Research, LLC
state: California
city: Denver
country: United States
facility: Mountain Mind. LLC
state: Colorado
city: Cromwell
country: United States
facility: CT Clinical Research
state: Connecticut
city: Hartford
country: United States
facility: Institute of Living
state: Connecticut
city: Fort Myers
country: United States
facility: Gulf Coast Clinical Research Center
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Florida
city: Miami
country: United States
facility: Optimus U Corporation
state: Florida
city: Atlanta
country: United States
facility: Advanced Discovery Research LLC
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center
state: Georgia
city: Chicago
country: United States
facility: Chicago Research Center, Incorporated
state: Illinois
city: Wichita
country: United States
facility: University of Kansas School of Medicine-Wichita
state: Kansas
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: O'Fallon
country: United States
facility: Psychiatric Care and Research Center
state: Missouri
city: Cherry Hill
country: United States
facility: Center For Emotional Fitness
state: New Jersey
city: Marlton
country: United States
facility: Hassman Research Institute
state: New Jersey
city: New York
country: United States
facility: Synexus Clinical Research US, Inc.
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Moosic
country: United States
facility: Global Medical Institutes, LLC, Scranton Medical Institute
state: Pennsylvania
city: Everett
country: United States
facility: Core Clinical Research
state: Washington
city: Caba
country: Argentina
facility: Fundación para el Estudio y Tratamiento de las Enfermedades Mentales (FETEM)
city: Cordoba
country: Argentina
facility: CEN (Centro Especializado Neurociencias)
city: Cordoba
country: Argentina
facility: Instituto DAMIC - Fundacion Rusculleda
city: La Plata
country: Argentina
facility: CENPIA-Centro de Estudios Neuropsiquiátricos y Psicológicos Integral Ambulatorio
city: La Plata
country: Argentina
facility: Clinica Privada de Salud Mental Santa Teresa de Avila
city: La Plata
country: Argentina
facility: Instituto de Neurociencias San Agustín
city: Rosario
country: Argentina
facility: Instituto Médico de la Fundación Estudios Clínicos
city: Rosario
country: Argentina
facility: Centro de Investigacion y Asistencia en Psiquiatria (CIAP)
city: Southport
country: Australia
facility: Griffith Health
state: Queensland
city: Frankston
country: Australia
facility: Peninsula Therapeutic and Research Group
state: Victoria
city: Melbourne
country: Australia
facility: Albert Road Clinic
state: Victoria
city: Melbourne
country: Australia
facility: Monash Alfred Psychiatry Research Centre
state: Victoria
city: Burgas
country: Bulgaria
facility: Mental Health Center "Prof. Dr. Ivan Temkov - Burgas" EOOD
city: Plovdiv
country: Bulgaria
facility: Filipopolis Ambulatory for Group Practice for Specialized Care in Psychiatry
city: Sofia
country: Bulgaria
facility: Medical Center Intermedica Ltd.
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Kelowna
country: Canada
facility: OCT Research ULC
state: British Columbia
city: Mississauga
country: Canada
facility: Braxia Scientific Corp. (CRTCE Mississauga)
state: Ontario
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health (CAMH)
state: Ontario
city: Hradec Kralove
country: Czechia
facility: Neuropsychiatry, s.r.o.
city: Kladno
country: Czechia
facility: Clinical Research Foundation s.r.o
city: Ostrava
country: Czechia
facility: MP Meditrine s.r.o.
city: Plzen
country: Czechia
facility: A-SHINE s.r.o
city: Prague
country: Czechia
facility: Clintrial s.r.o.
city: Prague
country: Czechia
facility: AD71 s.r.o.
city: Prague
country: Czechia
facility: INEP medical s.r.o.
city: Dijon
country: France
facility: HOP Dijon-Bourgogne
city: Douai
country: France
facility: CAB Médical Psyché
city: Elancourt
country: France
facility: CAB Ambroise Paré
city: Montpellier
country: France
facility: HOP la Colombière
city: Nantes
country: France
facility: HOP Saint-Jacques
city: Nice
country: France
facility: HOP Pasteur
city: Nîmes
country: France
facility: HOP Carémeau
city: Saint-Cyr-sur-Loire
country: France
facility: CTR Psychiatrique Universitaire
city: Toulouse
country: France
facility: HOP Purpan
city: Bad Homburg
country: Germany
facility: Zentrum für klinische Forschung Dr. med. I. Schöll GmbH
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Mannheim
country: Germany
facility: Zentralinstitut für seelische Gesundheit
city: Stralsund
country: Germany
facility: Praxis für Psychiatrie und Psychotherapie
city: Westerstede
country: Germany
facility: Studienzentrum Nord-West
city: Budapest
country: Hungary
facility: Obuda Health Center
city: Budapest
country: Hungary
facility: Semmelweis University
city: Gyongyos
country: Hungary
facility: Bugat Pal Hospital, Gyongyos
city: Chiba, Ichikawa
country: Japan
facility: National Center for Global Health and Medicine Kohnodai Hospital
city: Fukuoka, Fukuoka
country: Japan
facility: Kaku Mental Clinic
city: Fukuoka, Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Fukuoka, Fukuoka
country: Japan
facility: Kuramitsu Hospital
city: Hokkaido, Sapporo
country: Japan
facility: Hokudai-dori Mental Health Clinic
city: Hyogo, Amagasaki
country: Japan
facility: Arai Clinic
city: Hyogo, Kobe
country: Japan
facility: Tatsuta Clinic
city: Kanagawa, Kawasaki
country: Japan
facility: Kishiro Mental Clinic
city: Kanagawa,Sagamihara
country: Japan
facility: Yutaka Clinic
city: Kumamoto, Kumamoto
country: Japan
facility: Yuge Neuropsychiatric Hospital
city: Nagasaki, Nagasaki
country: Japan
facility: Arata Clinic
city: Nara, Kashihara
country: Japan
facility: Nara Medical University Hospital
city: Saga, Karatsu
country: Japan
facility: Rainbow and Sea Hospital
city: Saga, Tosu
country: Japan
facility: Inuo Hospital
city: Tokyo, Kodaira
country: Japan
facility: National Center of Neurology and Psychiatry
city: Tokyo, Minato-ku
country: Japan
facility: Tamachi mita cocoromi Clinic
city: Tokyo, Setagaya-ku
country: Japan
facility: Sancha Mental Clinic
city: Tokyo, Shibuya-ku
country: Japan
facility: Maynds Tower Mental Clinic
city: Tokyo, Shinjuku-ku
country: Japan
facility: Ichigaya Himorogi Clinic
city: Tokyo, Toshima-ku
country: Japan
facility: Ohwa Mental Clinic
city: Gdansk
country: Poland
facility: Synexus Polska SCM Sp. z o.o. Gdansku, Gdansk
city: Lodz
country: Poland
facility: Synexus Lodz Medical Center
city: Lodz
country: Poland
facility: Specialist Psychiatric Healthcare Centre in Lodz
city: Lublin
country: Poland
facility: Clinical Best Solutions
city: Lublin
country: Poland
facility: Centrum Medyczne "Luxmed" Sp. z o.o.
city: Poznan
country: Poland
facility: Synexus Poland, Branch in Poznan
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution "Mental Health Research Center"
city: Moscow
country: Russian Federation
facility: SBI of HC "Z. P. Solovyov Scientific&pract psychoneurolog.Cent"
city: Saratov
country: Russian Federation
facility: SHI "Reg.Clin.Psychiatric Hosp.of Saint Sophia"
city: Smolensk
country: Russian Federation
facility: FSBEI of HE Smolensk State Medical University
city: St. Petersburg
country: Russian Federation
facility: SBHI "Psychiatric Hospital #1 P.P.Kashchenko"
city: St. Petersburg
country: Russian Federation
facility: FSBI Bekhterev Net.Med.Res.Cen.of Psych&Neuro
city: St. Petersburg
country: Russian Federation
facility: LLC "MK-Med"
city: Banska Bystrica
country: Slovakia
facility: MUDr. Beata Dupejová
city: Bratislava
country: Slovakia
facility: J & J SMART, s.r.o., psychiatric clinic
city: Bratislava
country: Slovakia
facility: MENTUM s.r.o.
city: Kosice
country: Slovakia
facility: EPAMED s.r.o.
city: Kosice
country: Slovakia
facility: Psychiatricka klinika I.UN L. Pasteura
city: Svidnik
country: Slovakia
facility: CENTRUM ZDRAVIA R.B.K, s.r.o., psychiatric clinic
city: Trencin
country: Slovakia
facility: Pro mente sana s.r.o., Psychiatric clinic
city: Vranov nad Toplou
country: Slovakia
facility: Crystal Comfort s.r.o
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
city: Barcelona
country: Spain
facility: Hestia Palau
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Jerez de la Frontera
country: Spain
facility: Hospital Jerez de la Frontera
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Salamanca
country: Spain
facility: Centro de Salud de San Juan
Study officials:
References: