A Study to Test Different Doses of BI 1569912 in People With Depression Who Take Anti-depressive Medicine

A Phase II, 6-week, Multicenter, Randomized, Double Blind (Patient and Investigator) or Masked, Placebo Controlled, Dose-finding Trial to Evaluate the Efficacy, Tolerability, and Safety of Different Doses of Oral BI 1569912 as Adjunctive Therapy in MD

This study is open to adults between 18 and 65 with a type of depression (major depressive disorder) for whom previous treatments for depression did not work. The purpose of the study is to find out whether a medicine called BI 1569912 helps people with depression.

Participants continue their standard therapy throughout the study.

Participants are put into 4 groups by chance. 3 of the 4 groups take different doses of BI 1569912. 1 group takes placebo. Placebo tablets looks like BI 1569912 but do not contain any medicine. Participants take the tablets once a day for 6 weeks.

Participants are in the study for about 2 to 4 and a half months. During this time, they visit the study site at least 6 times. At the visits, doctors ask participants about their symptoms.

The participants answer questions about their depression symptoms. The results are compared between the groups. The doctors also regularly check the general health of participants.

Inclusion criteria:

1. Male and female participants, 18 to 65 years of age, both inclusively at the time of consent.

2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.

3. Women of childbearing potential (WOCBP) must be ready and able to use a highly effective method of birth control per ICH M3 (R2) that results in a low failure rate of less than 1% per year when used consistently and correctly plus one additional barrier method. A list of contraception methods meeting these criteria and instructions on the duration of use is provided in the participant information and in the study protocol.

4. Established diagnosis of major depressive disorder (MDD), single episode or recurrent, as confirmed at the time of screening by the mini-international neuropsychiatric interview (MINI) with a duration of current depressive episode ≥8 weeks at the time of screening visit.

5. Hamilton Depression Rating Scale-17 (HDRS-17) - Severity scale score >17.

6. A documented ongoing monotherapy treatment of ≥6 weeks at the randomisation visit, with an selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) specified in the investigator site file (ISF) at adequate dose (at least minimum effective dose as per prescribing information).

   • The participant must adhere to the screening visit dose of the background SSRI/SNRI until the end of the trial. Participants should be on a stable dose for at least 4 weeks prior to randomisation.
   • Participants, who, in addition to their monotherapy with an SSRI/SNRI, are taking additional low dose antidepressant medications for purposes other than treating depressive symptoms, are not excluded. The dose must be less than the lowest dose indicated for MDD.

7. In the current episode, participants have shown insufficient treatment response defined by less than 50% response to a maximum of 4 antidepressant treatments of adequate dose and treatment duration (according to Summary of Product Characteristics) as evaluated by the antidepressant treatment response questionnaire (ATRQ).

Exclusion criteria:

1. Per MINI, have ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar disorder, or delusional disorder.
2. Diagnosis with antisocial, paranoid, schizoid or schizotypal personality disorder, or MDD with psychotic features as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (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.
3. Diagnosis of any other mental disorder that was the primary focus of treatment within 6 months prior to screening (as per clinical discretion of the investigator).
4. History or presence (upon clinical examination) of seizure disorders or an increased risk of seizures (first degree relative with epilepsy), stroke, brain tumour or any other major neurological illness that could impact participation in the trial.
5. A current or recent history of clinically significant suicidal ideation with intent within the past 3 months, corresponding to a score of 4 or 5 for ideation on the Columbia-suicide severity rating scale (C-SSRS) or a suicidal attempt within the past year, as indicated by the C-SSRS at screening visit.
6. Participants with a body mass index (weight [kg]/height [m]²) lower than 18 kg/m² or greater than 40 kg/m² at screening.
7. Diagnosis of a moderate to severe substance related disorder within 6 months prior to screening visit (with exception of caffeine and tobacco).
8. Positive drug screen (amphetamines, opiates, cocaine, barbiturates, phencyclidine) at screening or Visit 1A (if applicable). Participants with positive cannabis and benzodiazepine drug tests can be included if the investigator confirms that there is no active substance related disorder. Further exclusion criteria apply.