Depressive Disorder, Major
Conditions
Brief summary
This study is open to adults between 18 and 65 years of age with a type of depression called major depressive disorder. The purpose of the study is to find out whether a medicine called BI 1569912 helps people with depression. Participants are put into 4 groups randomly, which means by chance. Three of the 4 groups take different doses of BI 1569912 and 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 2.5 months. During this time, they visit the study site at least 7 times. At the visits, doctors and their staff ask participants about their depression symptoms. At the end of the study, the results are compared between the groups to see whether the treatment works. The doctors also regularly check the general health of participants and take note of any unwanted effects.
Interventions
DRUG5 mg BI 1569912
Two 2.5 mg tablets of BI 1569912
DRUGPlacebo matching BI 1569912
Placebo matching BI 1569912
DRUG10 mg BI 1569912
One 10 mg tablet of BI 1569912
DRUG20 mg of BI 1569912
Two 10 mg tablets of BI 1569912
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female participants, 18 to 65 years of age, both inclusively at the time of consent * Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial * 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 * 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 the current depressive episode ≥8 weeks AND ≤24 months at the time of randomisation * Hamilton Depression Rating Scale-17 (HDRS-17) - Severity scale score ≥20 * Clinical Global Impression- Severity Scale (CGI-S) score ≥4
Exclusion criteria
* Per Mini International Neuropsychiatric Interview (MINI), have ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar disorder, or delusional disorder * 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 * 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) * Treatment failure to 2 or more antidepressants in the current episode, defined as less than 50% response to treatments administered at an adequate dose and duration as evaluated by the Antidepressant treatment response questionnaire (ATRQ) * 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 * 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 * Participants with a body mass index (weight \[kg\]/height \[m\]²) lower than 18 kg/m² or greater than 40 kg/m2 at screening * Diagnosis of a moderate to severe substance related disorder as defined by DSM-5 criteria within 6 months prior to screening visit (with exception of caffeine and tobacco) Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MADRS Total Score at Week 6 | MMRM included measurements at baseline, Day 8, Week 2, Week 4, and Week 6. Change from baseline values at Week 6 is reported. | The change from baseline at Week 6 in the total Montgomery-Åsberg Depression Rating Scale (MADRS) score is reported, calculated as \[Week 6 MADRS score\] - \[Baseline MADRS score\]. The MADRS score assessed the severity of symptoms in people with depression, consisting of 10 items. Each item was rated from 0 (no symptom) to 6 (severe symptom), with a total score ranging from 0 to 60 (0 = normal/absence of symptoms, 60 = severe depression). The least squares mean and 95% confidence intervals were estimated by a mixed model for repeated measures (MMRM) including the fixed categorical effects of treatment at each time point and the number of antidepressant treatments taken for the current episode (0/1), and the baseline MADRS total score at each time point as fixed continuous effects. The time point is treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements. |
Countries
Japan, United States
Participant flow
Recruitment details
Phase II dose finding multicentre, randomised, double-blind, placebo-controlled trial to examine the efficacy and safety of different doses of oral BI 1569912 once daily over a planned 6-week treatment period in adult patients with moderate to severe major depressive disorder (MDD). Participants were randomized to placebo or one of 3 doses of active BI 1569912 (5, 10, or 20 mg) in a 2:1:1:2 ratio.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 39.9 Years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 177 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 40 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 104 Participants |
| Sex: Female, Male Female | 122 Participants |
| Sex: Female, Male Male | 33 Participants |
| Total Montgomery-Åsberg Depression Rating Scale (MADRS) score | 32.0 Units on a scale STANDARD_DEVIATION 4.1 |
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 / 76 | 0 / 35 | 0 / 41 | 0 / 73 |
| other Total, other adverse events | 15 / 76 | 9 / 35 | 7 / 41 | 18 / 73 |
| serious Total, serious adverse events | 1 / 76 | 0 / 35 | 1 / 41 | 0 / 73 |
Outcome results
None listed