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

Boehringer Ingelheim243 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

243

Conditions

Depressive Disorder, Major

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (52)

Southwest Biomedical Research, LLC

Tucson, Arizona, United States

Excell Research Inc.

Oceanside, California, United States

NRC Research Institute

Orange, California, United States

Asclepes Research Centers-Panorama City-62905

Panorama City, California, United States

CT Clinical Research

Cromwell, Connecticut, United States

Outcomes

Primary Outcomes

Change From Baseline in MADRS Total Score at Week 6

Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-reported interview guide which evaluates core symptoms of depression. It consists of 10 items and each item is rated on a scale from 0 (no abnormality) to 6 (severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression). The Least Squares Mean (95 % confidence interval) were estimated by restricted maximum likelihood-based mixed model for repeated measures (REML-based MMRM) which includes the fixed categorical effects of treatment at each time point, cohort (with/without lead-in phase), and fixed continuous effects of baseline MADRS total score at each time point. The time point is treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements.

Time frame: MMRM included measurements from baseline and Day 8, Week 4, Week 6 after first drug administration. MMRM estimates of change from baseline to Week 6 in MADRS total score is reported.

Secondary Outcomes

Change From Baseline in MADRS Total Score at Day 8

Montgomery-Åsberg Depression Rating Scale (MADRS)s a clinician-reported interview guide which evaluates core symptoms of depression. It consists of 10 items, and each item is rated on a scale from 0 (no abnormality) to 6 (severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression). The Least Squares Mean (95 % confidence intervals) were estimated by restricted maximum likelihood-based mixed model for repeated measures (REML-based MMRM) which includes the fixed categorical effects of treatment at each time point, cohort (with/without lead-in phase), and fixed continuous effects of baseline MADRS total score at each time point. The time point is treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements.

Time frame: MMRM included measurements from baseline and Day 8, Week 4, Week 6 after first drug administration. MMRM estimates of change from baseline to Day 8 in MADRS total score is reported.

Response Defined as >=50% MADRS Reduction From Baseline at Day 8

Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-reported interview guide which evaluates core symptoms of depression. It consists of 10 items, and each item is rated on a scale from 0 (no abnormality) to 6 (severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression). Percentage of participants with a \>=50% reduction of the MADRS from baseline at Day 8 is reported. Percentages are rounded to one decimal place.

Time frame: Baseline and at Day 8.

Response Defined as >=50% MADRS Reduction From Baseline at Week 6

Time frame: At baseline and at Week 6.

Remission Defined as MADRS Total Score <=10 at Week 6

Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-reported interview guide which evaluates core symptoms of depression. It consists of 10 items, and each item is rated on a scale from 0 (no abnormality) to 6 (severe). The possible total score could range from 0 to 60 (from normal with absence of symptoms to severe depression). Percentage of participants with a MADRS total score \<=10 at Week 6 is reported. Percentages are rounded to one decimal place.

Time frame: At Week 6.

Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Day 8

SMDDS is a 16-item patient-reported measure where each item is rated from 0 ("Not at all/Never") to 4 ("Extremely/Always"). Total score ranges from 0-60, with higher scores indicating greater depression severity. Items 11 and 12 are combined by taking the higher score, then summed with the other 14 items. Least Squares Mean (95 % confidence interval) were estimated by restricted maximum likelihood-based mixed model for repeated measures (REML- based MMRM) with fixed categorical effects of treatment at each time point, cohort (with/without lead-in phase) and baseline MADRS total score (\</\>=24), and fixed continuous effects of baseline SMDDS total score at each time point. The time point is treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements.

Time frame: MMRM included measurements from baseline and Day 8 and at Week 4 after first drug administration. MMRM estimates of change from baseline to Day 8 in SMDDS total score is reported.

Change From Baseline in SMDDS Total Score at Week 4

The SMDDS is a 16-item patient-reported measure where each item is rated from 0 ("Not at all/Never") to 4 ("Extremely/Always"). Total score ranges from 0-60, with higher scores indicating greater depression severity. Items 11 and 12 are combined by taking the higher score, then summed with the other 14 items. Least Squares Mean (95 % confidence interval) were estimated by restricted maximum likelihood-based mixed model for repeated measures (REML- based MMRM) with fixed categorical effects of treatment at each time point, cohort (with/without lead-in phase) and baseline MADRS total score (\</\>=24), and fixed continuous effects of baseline SMDDS total score at each time point. The time point is treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements.

Time frame: MMRM included measurements from baseline and Day 8 and at Week 4 after first drug administration. MMRM estimates of change from baseline to Week 4 in SMDDS total score is reported.