Depressive Disorder, Major
Conditions
Brief summary
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.
Interventions
DRUGBI 1569912
Tablets
DRUGPlacebo
Tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MADRS Total Score at Week 6 | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MADRS Total Score at Day 8 | 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. | 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. |
| Response Defined as >=50% MADRS Reduction From Baseline at Day 8 | Baseline and 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. |
| Response Defined as >=50% MADRS Reduction From Baseline at Week 6 | At baseline and 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 \>=50% reduction of the MADRS from baseline at Week 6 is reported. Percentages are rounded to one decimal place. |
| Remission Defined as MADRS Total Score <=10 at Week 6 | 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. |
| Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Total Score at Day 8 | 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. | 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. |
| Change From Baseline in SMDDS Total Score at Week 4 | 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. | 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. |
Countries
Belgium, Bulgaria, China, Czechia, Germany, Japan, United States
Participant flow
Recruitment details
A Phase II dose-finding trial to examine the efficacy and safety of oral BI 1569912 once daily over a 6-week treatment period in adult patients with moderate-to-severe major depressive disorder (MDD) who failed to respond to 1 or more antidepressants of adequate dose and duration in the current episode and who were still on stable treatment with current selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI).
Pre-assignment details
All patients were screened for eligibility prior to participation in the trial, to ensure that they met all inclusion and none of the exclusion criteria. Patients who met all other eligibility criteria but were not on an SSRI/SNRI at Visit 1, had the option to undergo a 6-week open label lead-in phase with SSRI/SNRI. These patients were reassessed at Visit 1A to determine eligibility to be randomized to the trial.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 46.9 Years STANDARD_DEVIATION 14.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Montgomery-Åsberg Depression Rating Scale at baseline | 32.3 score on a scale STANDARD_DEVIATION 5 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 44 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 153 Participants |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 79 | 0 / 40 | 1 / 41 | 0 / 83 |
| other Total, other adverse events | 14 / 79 | 8 / 40 | 3 / 41 | 16 / 83 |
| serious Total, serious adverse events | 1 / 79 | 0 / 40 | 1 / 41 | 1 / 83 |
Outcome results
None listed