Major Depressive Disorder
Conditions
Brief summary
The purpose of this 14 week, randomized, double-blind, placebo controlled study is to assess the safety and efficacy of brexipiprazole to placebo as adjunctive treatment to an assigned open-label marketed antidepressant therapy (ADT) in patients with Major Depressive Disorder.
Interventions
DRUGBrexpiprazole
Tablets, Oral, once daily, 14 weeks
DRUGPlacebo
Tablets, Oral, once daily, 14 weeks
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Outpatients, or inpatients at the time of informed consent whose treatment status can be successfully shifted to outpatient status before enrollment in the antidepressant treatment period * Male and female patients ≥ 20 to \< 65 years of age (at the time of informed consent) * Patients who have a level of comprehension sufficient to allow them to give written informed consent to all of the observation/examination/evaluation items specified in the protocol, and who can understand the contents of the trial * Patients with a DSM-5 classification-based diagnosis of major depressive disorder, single episode or major depressive disorder, recurrent episode, and whose current episode has persisted for at least 8 weeks
Exclusion criteria
* Women who are pregnant or breastfeeding or who have positive pregnancy test (urine) results at screening * Sexually active male subjects or sexually active female subjects of childbearing potential, who will not agree to practice 2 different methods of birth control or to remain abstinent during the trial and for 30 days after the final IMP administration. For birth control, 2 of the following methods must be used: vasectomy, tubal ligation, vaginal diaphragm, intra-uterine contraceptive device (IUD), oral contraceptives, or condom with spermicide. * Patients with a treatment history showing that all antidepressants (including those not used for the current major depressive episode) cannot be tolerated * Patients with a history of electroconvulsive therapy * Patients with a diagnosis of any of the following diseases according to DSM-5 1. Neurocognitive disorders 2. Schizophrenia spectrum and other psychotic disorders 3. Bipolar and related disorders 4. Feeding and eating disorders 5. Obsessive-compulsive disorder 6. Panic disorder 7. Posttraumatic stress disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Changes From Baseline (Week 8 of the Antidepressant Treatment Period [Phase A]) in the MADRS Total Scores at Week 6 of the Double-blind Period (Phase B). | Baseline (the end of Phase A), at completion of administration (Week 6). | The MADRS was a clinician-rated scale which evaluated the level of depression. The MADRS consisted of 10 items assessing apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thought. Each item was scored from 0 to 6, with higher scores indicating worse condition. Summed subscales were combined to compute a total score. Total score ranges from 0 to 60, with higher scores indicating worse condition.The mean changes were compared between antidepressant treatments and brexpiprazole as adjunctive therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CGI-I Improvement Rate at Week 6 of the Double-blind Period (Phase B) | Baseline (the end of Phase A), at completion of administration (Week 6). | Clinical Global Impression - Improvement (CGI-I) improvement rate: the proportion of participants who score 1 or 2 on the CGI-I scale at Week 6 of the double-blind period (Phase B). The CGI-I Scale was a clinician-rated scale which assessed the total improvement of the participant's condition compared to that at baseline. Scores range from 0 to 7:0 = Not assessed, 1= Very much improved, 2 = Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Higher scores indicated worse condition. |
Countries
Japan
Participant flow
Recruitment details
This trial was conducted in 740 participants from 145 trial sites in Japan.
Pre-assignment details
Adults with major depressive disorder as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and who had not responded sufficiently to antidepressants (SSRIs or SNRIs) were included.
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole 1 mg Participants received brexpiprazole 1 mg tablet once daily for 6 weeks. | 248 |
| Brexpiprazole 2 mg Participants received brexpiprazole 1 mg tablet once daily for 1 week followed by 2 mg tablet once daily for 5 weeks. | 245 |
| Placebo Participants received placebo tablet once daily for 6 weeks. | 243 |
| Total | 736 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 18 | 3 |
| Overall Study | Physician Decision | 1 | 0 | 2 |
| Overall Study | Protocol Violation | 3 | 8 | 5 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 1 |
Baseline characteristics
| Characteristic | Brexpiprazole 1 mg | Brexpiprazole 2 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 248 Participants | 245 Participants | 243 Participants | 736 Participants |
| Age, Continuous | 40.9 years STANDARD_DEVIATION 10.8 | 40.0 years STANDARD_DEVIATION 10.7 | 39.8 years STANDARD_DEVIATION 10.8 | 40.2 years STANDARD_DEVIATION 10.8 |
| Race/Ethnicity, Customized Asian | 248 Participants | 245 Participants | 243 Participants | 736 Participants |
| Region of Enrollment Japan | 248 participants | 245 participants | 243 participants | 736 participants |
| Sex: Female, Male Female | 116 Participants | 102 Participants | 105 Participants | 323 Participants |
| Sex: Female, Male Male | 132 Participants | 143 Participants | 138 Participants | 413 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 250 | 0 / 246 | 0 / 244 |
| other Total, other adverse events | 108 / 250 | 153 / 246 | 92 / 244 |
| serious Total, serious adverse events | 3 / 250 | 3 / 246 | 2 / 244 |
Outcome results
Primary
Mean Changes From Baseline (Week 8 of the Antidepressant Treatment Period [Phase A]) in the MADRS Total Scores at Week 6 of the Double-blind Period (Phase B).
The MADRS was a clinician-rated scale which evaluated the level of depression. The MADRS consisted of 10 items assessing apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thought. Each item was scored from 0 to 6, with higher scores indicating worse condition. Summed subscales were combined to compute a total score. Total score ranges from 0 to 60, with higher scores indicating worse condition.The mean changes were compared between antidepressant treatments and brexpiprazole as adjunctive therapy.
Time frame: Baseline (the end of Phase A), at completion of administration (Week 6).
Population: FAS (Same as Baseline Analysis Population Description)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 1 mg | Mean Changes From Baseline (Week 8 of the Antidepressant Treatment Period [Phase A]) in the MADRS Total Scores at Week 6 of the Double-blind Period (Phase B). | -8.5 Units on a scale | Standard Error 0.47 |
| Brexpiprazole 2 mg | Mean Changes From Baseline (Week 8 of the Antidepressant Treatment Period [Phase A]) in the MADRS Total Scores at Week 6 of the Double-blind Period (Phase B). | -8.2 Units on a scale | Standard Error 0.47 |
| Placebo | Mean Changes From Baseline (Week 8 of the Antidepressant Treatment Period [Phase A]) in the MADRS Total Scores at Week 6 of the Double-blind Period (Phase B). | -6.7 Units on a scale | Standard Error 0.47 |
Comparison: Statistical analysis to compare brexpiprazole 2 mg/day and placebo was performed at Week 6.p-value: 0.031295% CI: [-2.7, -0.1]MMRM
Comparison: Statistical analysis to compare brexpiprazole 1 mg/day and placebo was performed at Week 6.p-value: 0.008995% CI: [-3, -0.4]MMRM
Secondary
CGI-I Improvement Rate at Week 6 of the Double-blind Period (Phase B)
Clinical Global Impression - Improvement (CGI-I) improvement rate: the proportion of participants who score 1 or 2 on the CGI-I scale at Week 6 of the double-blind period (Phase B). The CGI-I Scale was a clinician-rated scale which assessed the total improvement of the participant's condition compared to that at baseline. Scores range from 0 to 7:0 = Not assessed, 1= Very much improved, 2 = Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Higher scores indicated worse condition.
Time frame: Baseline (the end of Phase A), at completion of administration (Week 6).
Population: FAS (Same as Baseline Analysis Population Description)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole 1 mg | CGI-I Improvement Rate at Week 6 of the Double-blind Period (Phase B) | 35.1 percentage of participants |
| Brexpiprazole 2 mg | CGI-I Improvement Rate at Week 6 of the Double-blind Period (Phase B) | 35.1 percentage of participants |
| Placebo | CGI-I Improvement Rate at Week 6 of the Double-blind Period (Phase B) | 29.6 percentage of participants |
Comparison: Statistical analysis to compare brexpiprazole 2 mg/day and placebo was performed at Week 6.p-value: 0.196495% CI: [-2.8, 13.8]Chi-squared
Comparison: Statistical analysis to compare brexpiprazole 1 mg/day and placebo was performed at Week 6.p-value: 0.196995% CI: [-2.8, 13.7]Chi-squared