A Study to Test the Effect of Different Doses of BI 1358894 and Quetiapine in People With Depression
A Study to Test the Effect of Different Doses of BI 1358894 and Quetiapine in People With Depression
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 twice a day. Placebo tablets
 look like BI 1358894 or quetiapine tablets but do not contain any medicine.

 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.
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 ≤ 12 months at the time of screening visit

 -  Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 26 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 ≥ 8 weeks at the screening visit, with 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 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 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 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)