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

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, asconfirmed by a trained site based rater AND interactive, computer administeredMADRS. The difference in the rater and computer administered MADRS must not exceedmore than 7 points (for details refer to section 6.2). In addition, trialparticipants must have a score of ≥ 3 on the Reported Sadness Item on both MADRSscales (computer administered and rater-administered MADRS)

• A documented ongoing monotherapy treatment of ≥ 4 weeks at the screening visit, withbupropion or a protocol specified Selective Serotonin Reuptake Inhibitor (SSRI) orSerotonin Norepinephrine Reuptake Inhibitor (SNRI) (refer to the ISF) at adequatedose (at least minimum effective dose as per prescribing information and asconfirmed 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 ofconsent

• Women who are of child-bearing potential (WOCBP)1 must be able and willing, asconfirmed by the investigator, to use two methods of contraception which include onehighly effective method of birth control per ICH M3 (R2) that result in a lowfailure rate of less than 1%, plus one additional barrier

• Signed and dated written informed consent in accordance with ICH-GCP and locallegislation 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, schizoaffectivedisorder, schizophreniform disorder, bipolar disorder, delusional disorder or MDDwith psychotic features as assessed by the Structured Clinical Interview for DSM-5Clinical Trials (SCID-5) at the time of screening

• Diagnosis of any other mental disorder (in addition to those as described inExclusion Criterion #1) that was the primary focus of treatment within 6 monthsprior to screening or at baseline (as per clinical discretion of the investigator)

• Diagnosis with antisocial, paranoid, schizoid or schizotypal personality disorder asper DSM-5 criteria, at the time of screening visit. Any other personality disorderat screening visit that significantly affects current psychiatric status and likelyto 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 neurologicalillness that can impact participation in the trial

• History of more than 2 unsuccessful monotherapy treatments (at adequate dosage andduration, per local prescribing information of the product) with an approvedantidepressant medication for the current ongoing major depressive episode. Theseinclude ongoing monotherapy treatment with bupropion or a protocol specified SSRI orSNRI as described in Inclusion Criterion #3

• Any suicidal behavior in the past 12 months prior to screening (per investigatorjudgement including an actual attempt, interrupted attempt, aborted attempt, orpreparatory 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, oractive suicidal thought with method, intent and plan)