A Study in People With Depression to Test the Effects of BI 1358894 on Parts of the Brain That Are Involved in Emotions

Study Overview
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Brief Summary
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To assess the effect of a single dose of BI 1358894 compared to placebo on BOLD responses in modulating brain processing of emotional and cognitive stimuli on the amygdala and related brain structure using fMRI in in unmedicated patients with depression.

Official Title
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A Single Dose, Randomized, Placebo Controlled Phase I Study on the Effects of BI 1358894 on Functional MRI Measurements in an Emotional Processing Paradigm in Patients With Major Depressive Disorder

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Drug: BI 1358894
* Drug: Placebo matching BI 1358894
* Drug: Citalopram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients having a diagnosis of a MDD according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) (single episode or recurrent) with a MADRS total score between ≥ 7 and < 26 at screening. Male or female aged 18 to 45 years, inclusive at screening. Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control. Patients must be, in the opinion of the Investigator, capable of and eligible for completing the fMRI and tasks. Patients must be right-handed. Patients must have acceptable weight as defined by BMI (weight [kg]/height [m]²) range of 18 to 30 kg/m², inclusive at Visit 1. Patients must be a non-smoker or light smoker (≤ 5 cigarettes per day). Patients must have signed the informed consent form prior to the first study-related procedure indicating they understand the purpose of and procedures required for the study and are willing to participate in the study. Further inclusion criteria apply Exclusion Criteria: Meeting any diagnostic criteria for a major psychiatric disorder (other than MDD), as determined by DSM-V at screening. Has received a prescribed medication (including antidepressants) within 28 days prior to Visit 1 (apart from the contraceptive pill) or having received over the counter medication (including pain killers) within 10 days prior to screening. Participants who have taken prescription medication may still be entered into the study, if, in the opinion of the Investigator, the medication received will not interfere with the study procedures or compromise safety. Patients where it is foreseen (per investigator judgement) that a delay of initiation of standard of care therapy for the depressive disorder to 14 days after day 1 of Visit 2 is medically not justifiable. A history of alcohol or substance dependence or abuse within the last 12 months from Visit 1. Has a current or recent history of clinically significant suicidal ideation within the past 6 months, corresponding to a score of 4 or 5 for ideation on the C-SSRS, or a history of suicidal behavior within the past year, as validated by the C-SSRS at screening or treatment visit. Has a history of, or presents (in the opinion of the Investigator) with, significant neurological or psychiatric conditions (such as stroke, traumatic brain injury, seizures, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, schizophrenia, blackouts requiring hospitalisation). A planned medical treatment within the study period that might interfere with the study procedures. Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 1358894<br> | Drug: BI 1358894<br>* Film-coated tablet<br>|
| Experimental: Citalopram<br> | Drug: Citalopram<br>* Film-coated tablet<br>|
| Experimental: Placebo matching BI 1358894<br> | Drug: Placebo matching BI 1358894<br>* Film-coated tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Blood Oxygenation Level Depend (BOLD) Signal % change in an emotional paradigm, based on the emotional faces from the Warsaw set of Emotional Facial Expression Pictures (WSEFEP) | The primary endpoint was the mean BOLD signal % change in an emotional paradigm, based on the emotional faces from the Warsaw Set of Emotional Facial Expression Pictures (WSEFEP) in the corticolimbic system comprising the following eight brain regions of interest: Amygdala left Amygdala right Dorsolateral prefrontal cortex left Dorsolateral prefrontal cortex right Insula left Insula right Anterior cingulate cortex left Anterior cingulate cortex right | Up to 6 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean BOLD signal % change in an emotional paradigm in the corticolimbic system using the affective pictures of the Open Affective Standardised Image Set (OASIS). | The secondary endpoint was the mean BOLD signal % change in an emotional paradigm (affective picture set - OASIS task) in the corticolimbic system, consisting of eight brain regions: Amygdala left Amygdala right Dorsolateral prefrontal cortex left Dorsolateral prefrontal cortex right Insula left Insula right Anterior cingulate cortex left Anterior cingulate cortex right | Up to 6 hours. |