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

NCT03854578 | Completed Phase 1 Results

• 2 other identifiers: 1402-00032017-004763-12
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Mean BOLD Signal % Change in an Emotional Paradigm in the Corticolimbic System Using the Affective Pictures of the Open Affective Standardised Image Set (OASIS).

  A 50 min scan, 6 hours following drug intake.

Study Arms (3)

BI 1358894

EXPERIMENTAL

Drug: BI 1358894

Citalopram

EXPERIMENTAL

Drug: Citalopram

Placebo matching BI 1358894

EXPERIMENTAL

Drug: Placebo matching BI 1358894

Interventions

BI 1358894 DRUG

Film-coated tablet

BI 1358894

Placebo matching BI 1358894 DRUG

Film-coated tablet

Placebo matching BI 1358894

Citalopram DRUG

Film-coated tablet

Citalopram

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Related Publications (1)

• Grimm S, Keicher C, Paret C, Niedtfeld I, Beckmann C, Mennes M, Just S, Sharma V, Fuertig R, Herich L, Mack S, Thamer C, Schultheis C, Weigand A, Schmahl C, Wunder A. The effects of transient receptor potential cation channel inhibition by BI 1358894 on cortico-limbic brain reactivity to negative emotional stimuli in major depressive disorder. Eur Neuropsychopharmacol. 2022 Dec;65:44-51. doi: 10.1016/j.euroneuro.2022.10.009. Epub 2022 Nov 4.

  PMID: 36343427 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

TRPC inhibitor BI 1358894; Citalopram

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: February 26, 2019
• Study Start: March 12, 2019
• Primary Completion: August 27, 2019
• Study Completion: September 23, 2019
• Last Updated: February 25, 2025
• Results First Posted: February 25, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)