Overview

The main objectives of this trial are to evaluate the efficacy and safety of oral BI 1358894 compared to placebo over a 6-week treatment period in participants with Major Depressive Disorder (MDD) and with inadequate response to antidepressants (SSRI or SNRI) utilizing a decentralized clinical trial (DCT) model.

Eligibility

Inclusion Criteria:

• Established diagnosis of Major Depressive Disorder, single episode or recurrent, as confirmed at the time of screening by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders v5 (DSM-5, SCID-5), with a duration of current depressive episode 8 weeks and 12 months at the time of screening visit.
• Montgomery-sberg Depression Rating Scale (MADRS) total score 22 at screening, as confirmed by a trained rater. In addition, trial participants must have a score of 3 on item number 2 on MADRS.
• A documented ongoing monotherapy treatment of 8 weeks at the screening visit, with a protocol specified SSRI or 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 of child-bearing potential (WOCBP)2 able and willing to use two methods of contraception, which include one highly effective method of birth control per ICH M3 (R2) that results in a low failure rate of less than 1%, plus one barrier method.
• 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 (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).
• Further exclusion criteria apply