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

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

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.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Drug: BI 1358894; Drug: Citalopram; Drug: Placebo matching BI 1358894

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 1358894	Drug: BI 1358894; Film-coated tablet
Experimental: Citalopram	Drug: Citalopram; Film-coated tablet
Experimental: Placebo matching BI 1358894	Drug: Placebo matching BI 1358894; Film-coated tablet

What is the study measuring?

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	A 50 min scan, 6 hours following drug intake.

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	A 50 min scan, 6 hours following drug intake.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): August 27, 2019
• Study Completion (Actual): September 23, 2019

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: February 25, 2019
• First Posted (Actual): February 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Antidepressive Agents; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: 1402-0003; 2017-004763-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No