Depressive Disorder, Major
Conditions
Brief summary
This study is open to adults between 18 and 65 years of age who have depression (major depressive disorder). People with a current depressive episode lasting between 2 months and one and a half years can join the study. This study is for people for whom existing treatments for depression do not work sufficiently. The purpose of this study is to test how well a medicine called BI 1569912 is tolerated and whether it may help people with depression. It is planned to test 4 different dosages of BI 1569912 in this study. Each participant gets either one BI 1569912 dosage or placebo. It is decided randomly, which means by chance, who gets which treatment. Participants take BI 1569912 or placebo as tablets once during the study. Placebo tablets look like BI 1569912 tablets but do not contain any medicine. Participants also continue taking their usual medicine for depression throughout the study. Participants are in the study for about 5 weeks. During this time, they visit the study site 4 times, with a stay at the study site for 9 days. The doctors check the health of the participants and note any health problems that could have been caused by BI 1569912. The participants fill in questionnaires about their depression symptoms.
Interventions
DRUG5 mg BI 1569912
BI 1569912Moderate-to-severe Major Depressive Disorder (MDD) patients on stable antidepressants (i.e. selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI)) took a single dose of 5 milligram (mg) BI 1569912 (1 BI 1569912 5 mg tablet and 3 placebo tablets), orally in the morning.
DRUG20 mg BI 1569912
Moderate-to-severe Major Depressive Disorder (MDD) patients on stable antidepressants (i.e. selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI)) took a single dose of 20 milligram (mg) BI 1569912 (4 BI 1569912 5 mg tablets), taken orally in the morning.
DRUGPlacebo
Moderate-to-severe Major Depressive Disorder (MDD) patients on stable antidepressants (i.e. selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI)) took four placebo tablets matching in size and weight to BI 1569912 5 mg tablets, taken orally in the morning.
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
1. Established diagnosis of Major Depressive Disorder (MDD) as confirmed at the time of screening by the Mini International Neuropsychiatric Interview (MINI), with a duration of current depressive episode ≥ 8 weeks and ≤ 24 months at the time of screening visit. 2. At least moderate severity of MDD confirmed by a trained site-based rater, at screening and Visit 2 day 1 (i.e. prior to randomisation). For patients who are not on an SSRI at Visit 1, MDD must be confirmed additionally at Visit 1 A. 3. In the current episode, patients have shown insufficient treatment response (defined by less than 50 % response to one or more antidepressant drugs of adequate dose and treatment duration (according to Summary of Product Characteristics) as evaluated by Antidepressant Treatment Response Questionnaire (ATRQ). 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. Use of bupropion is not allowed. 4. Documented ongoing monotherapy treatment of ≥ 6 weeks at randomisation (i.e. Visit 2 day 1) with a protocol specified Selective Serotonin Reuptake Inhibitors (SSRI) or Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) at adequate dose (according to ATRQ assessment). sampling at Visit 1). Patients who are not on an SSRI at Visit 1 will undergo a lead in phase as described in the Flow Chart. Patients who meet all the eligibility criteria but are not on an SSRI/SNRI at Visit 1, will have the option to undergo a 6 week open label lead in phase with SSRI/SNRI. These patients will be reassessed at Visit 1A to determine eligibility to be randomized to the trial. 5. Male or female patients, aged 18 to 65 years at screening. If Women of childbearing potential (WOCBP) are included, they have to be able and willing to use two methods of contraception which include one highly effective method of birth control per ICH M3 (R2) that result in a low failure rate of less than 1 %, plus one additional barrier method. If men who are able to father a child, are willing to participate, they have to use an adequate form of effective contraception for the duration of study participation and for at least 28 days after treatment has ended. 6. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. Please note complete sexual abstinence is allowed when this is in line with the preferred and usual lifestyle of the patient (note: periodic abstinence such as calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception) - (in this specific case the barrier methods, as mentioned below, are not applicable). Sexual abstinence as a contraceptive method will not be allowed for WOCBP who are heterosexually active.
Exclusion criteria
1. Patient had met diagnostic criteria per Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) for schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar disorder, delusional disorder or MDD with psychotic features at any time point in the patient's life. 2. Diagnosis with antisocial, paranoid, schizoid, schizotypical or Borderline personality disorder as per DSM-5 criteria at the time of screening visit. Any other personality disorder at screening visit that significantly affects current psychiatric status and is likely to impact trial participation, as per the judgement of investigator. 3. Diagnosis of any other mental disorder (in addition to those as described in Exclusion Criterion #1 and #2) that was the primary focus of treatment within 6 months prior to screening, as per clinical discretion of the investigator. 4. Patients with a Body Mass Index (weight \[kg\]/height \[m\]²) lower than 18 kg/m² at screening. 5. Diagnosis of a moderate to severe substance-related disorder within the last 6 months before screening visit (with exception of caffeine and tobacco). 6. Use of Ketamine/S-Ketamine for the current ongoing depressive episode. 7. Stable treatment with benzodiazepines and/or nonbenzodiazepine hypnotics. (Note: As needed (PRN) use of benzodiazepines and/or nonbenzodiazepine hypnotics may be acceptable except for the trial period Day -1 to Day 2). Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Decrease From Baseline (Peak Decrease) in Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Any Day Within a 7-day Interval | Evaluations taken at baseline (day -63 to -3) and on day 1, 2, 4, 6 and 8 (with trial drug intake on day 1). | Maximum decrease from baseline (peak decrease) in Montgomery-Åsberg Depression Rating Scale (MADRS) score at any day within a 7-day interval. The MADRS evaluates ten core symptoms of depression. Nine of the items are based upon patient reports and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). The possible total score is the sum of all items and could range from 0 to 60 (from normal with absence of symptoms to severe depression). Values presented are based on an analysis of covariance (ANCOVA) model, including treatment as discrete fixed effect and baseline MADRS total score as continuous fixed effect. |
| Number of Patients With Drug-related Adverse Events | The on treatment period + Follow up period, up to 15 days. | Number of patients with any drug-related Adverse Events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Åsberg Depression Rating Scale (MADRS) Area Under the Curve (AUC) 0-166:30 | Scale recorded at 7:00 hour (h) (Day 1), 22:30 h (Day 2), 70:30 h (Day 4), 118:30 h (Day 6), and 166:30 h (Day 8) post dose. | Montgomery-Åsberg Depression Rating Scale (MADRS) Area under the curve (AUC) 0-166:30, defined as the area under the response curve from pre-dose to the last measurement during inpatient stay at 166:30 h using the trapezoidal rule divided by full duration (166.5 h). The MADRS evaluates ten core symptoms of depression. Nine of the items are based upon patient reports and one is on the rater's observation (apparent sadness) during the rating interview. MADRS items are rated on a 0-6 continuum (0=no abnormality, 6=severe). The possible total score is the sum of all items and could range from 0 to 60 (from normal with absence of symptoms to severe depression). Values presented are based on an analysis of covariance (ANCOVA) model, including treatment as discrete fixed effect and baseline MADRS total score as continuous fixed effect. |
Countries
United States
Participant flow
Recruitment details
This was a single dosing, placebo-controlled, randomised, double-blinded (investigator and patient), parallel group trial in moderate-to-severe Major Depressive Disorder (MDD) patients on stable antidepressants (i.e. selective serotonin reuptake inhibitors \[SSRI\] or serotonin-norepinephrine reuptake inhibitors \[SNRI\]).
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 | 47.8 years STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Montgomery-Åsberg Depression Rating Scale (MADRS) score | 34.6 Score on a scale STANDARD_DEVIATION 5.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 27 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 3 / 19 | 5 / 20 | 1 / 20 |
| serious Total, serious adverse events | 0 / 19 | 0 / 20 | 0 / 20 |
Outcome results
None listed