Major Depressive Disorder
Conditions
Brief summary
This trial is a 52-week study to assess the safety of long-term use of brexpiprazole as adjunctive therapy in combination with an antidepressant.
Interventions
DRUGBrexpiprazole
2 mg/day (starting dose 1mg/day) of Brexpiprazole will be orally administered once daily
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Rollover subjects 1. Outpatients 2. Subjects who have completed the double-blind period of the double-blind trial and can commence the treatment period of this trial within 28 days from the completionof the double-blind period of the double-blind trial 3. Subjects 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 4. Subjects with a DSM-5 classification-based diagnosis of major depressive disorder, single episode or major depressive disorder, recurrent episode * New subjects 1. Outpatients 2. Male and female patients ≥ 65 years of age (at the time of informed consent) 3. Subjects 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 4. Patients with a DSM-5 classification-based diagnosis of major depressive disorder, single episode or major depressive disorder, recurrent episode whose current episode has persisted for at least 8 weeks
Exclusion criteria
* Rollover subjects 1. Female subjects who are pregnant or breastfeeding or who have positive pregnancy test (urine) results at baseline 2. 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. 3. Subjects who experience a change to the manic state in the antidepressant treatment period of the double-blind trial 4. Subjects who are discovered to not meet the inclusion criteria or to fall under any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Frequency of Subjects With Treatment-Emergent Adverse Events (TEAEs) | From baseline to week 52 | A treatment-emergent adverse event (TEAE) was defined as an AE that started after start of investigational medicinal product (IMP) treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Changes From Baseline in Montgomery Åsberg Depression Rating Scale(MADRS) Total Scores at Week 52(LOCF) | Baseline and Week 52(LOCF) | The MADRS was a clinician-rated scale which evaluated the level of depression.The MADRS consists of 10 items assessed 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 Proportion of Subjects Who Score 1 or 2 on the Clinical Global Impression-Improvement(CGI-I) Scale at Week 52(LOCF) | Baseline and Week 52 (LOCF) | The CGI-I Scale was clinician-rated scale which assessed the total improvement of the patient'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 indicate worse condition. |
| Mean Changes From Baseline in Clinical Global Impression-Severity of Illness(CGI-S) at Week 52(LOCF) | Baseline and Week 52 (LOCF) | The CGI-S Scale was a clinician-rated scale which assessed how mentally ill the patient is at the time. Scores range from 0 to 7: 0 = Not assessed, 1= Normal, not at all ill, 2 =Borderline mentally ill, 3= Mildly ill, 4= Moderately ill, 5= Markedly ill, 6= Severely ill, 7= Among the most extremely ill patients. Higher scores indicate worse condition. |
| Mean Changes From Baseline in Hamiliton Depression Rating Scale(HAM-D) Item Total Scores at Week 52(LOCF) | Baseline and Week 52 (LOCF) | The HAM-D was a clinician-rated scale which evaluated the level of depression. The HAM-D consists of 17 items such as depression mood, feeling of guilt, suicide, insomnia, work and activities, retardation, and so on. Each item was scored from 0 to 2, 3 or 4, with higher scores indicating worse condition. Summed subscales were combined to compute a total score. Total score ranges from 0 to 53 , with higher score indicating worse condition. |
| Mean Changes From Baseline in Sheehan Disability Scale (SDS) Scores at Week 52(LOCF) | Baseline and Week 52 (LOCF) | SDS Scale was a patient-rated scale which assessed the degree of impairment for each of 3 items (work/school, social life, and family life/home responsibilities) on a 11-point scale ranging from 0 to 10. The mean SDS score was the mean of scores for 3 items. Higher scores indicate worse condition. |
Countries
Japan
Participant flow
Recruitment details
This trial was conducted in 248 participants in Japan. Of the 248 subjects who were administered investigational medicinal product, the efficacy analysis set and the safety analysis set comprised 247 subjects (216 rollover subjects, 31 newly enrolled subjects) of the total brexpiprazole population.
Participants by arm
| Arm | Count |
|---|---|
| New Subjects Newly entering elderly patients with major depressive disorder, aged 65 and over. 2 mg/day (starting dose 1mg/day) of Brexpiprazole were orally administered once daily. | 31 |
| Rollover Subjects Participants who rolled over from, and received blinded brexpiprazole or placebo in the randomized, double-blind, placebo-controlled Phase 2/3 efficacy studies (331-102-00058); 2 mg/day (starting dose 1mg/day) of Brexpiprazole were orally administered once daily | 216 |
| Total | 247 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 18 | 48 |
| Overall Study | Lack of Efficacy | 1 | 3 |
| Overall Study | Non-compliance With Study Drug | 0 | 1 |
| Overall Study | Physician Decision | 1 | 4 |
| Overall Study | Protocol Violation | 0 | 8 |
| Overall Study | Withdrawal by Subject | 5 | 20 |
Baseline characteristics
| Characteristic | New Subjects | Rollover Subjects | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 31 Participants | 0 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 216 Participants | 216 Participants |
| Age, Continuous | 70.3 Years STANDARD_DEVIATION 4.5 | 40.7 Years STANDARD_DEVIATION 10.3 | 44.4 Years STANDARD_DEVIATION 13.9 |
| Race/Ethnicity, Customized Asian | 31 Participants | 216 Participants | 247 Participants |
| Region of Enrollment Japan | 31 participants | 216 participants | 247 participants |
| Sex: Female, Male Female | 18 Participants | 83 Participants | 101 Participants |
| Sex: Female, Male Male | 13 Participants | 133 Participants | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 1 / 216 |
| other Total, other adverse events | 30 / 31 | 201 / 216 |
| serious Total, serious adverse events | 1 / 31 | 8 / 216 |
Outcome results
Primary
The Frequency of Subjects With Treatment-Emergent Adverse Events (TEAEs)
A treatment-emergent adverse event (TEAE) was defined as an AE that started after start of investigational medicinal product (IMP) treatment.
Time frame: From baseline to week 52
Population: The safety analysis set comprised subjects who have received at least 1 dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| New Subjects | The Frequency of Subjects With Treatment-Emergent Adverse Events (TEAEs) | 96.8 percentage of participants |
| Rollover Subjects | The Frequency of Subjects With Treatment-Emergent Adverse Events (TEAEs) | 93.1 percentage of participants |
Secondary
Mean Changes From Baseline in Clinical Global Impression-Severity of Illness(CGI-S) at Week 52(LOCF)
The CGI-S Scale was a clinician-rated scale which assessed how mentally ill the patient is at the time. Scores range from 0 to 7: 0 = Not assessed, 1= Normal, not at all ill, 2 =Borderline mentally ill, 3= Mildly ill, 4= Moderately ill, 5= Markedly ill, 6= Severely ill, 7= Among the most extremely ill patients. Higher scores indicate worse condition.
Time frame: Baseline and Week 52 (LOCF)
Population: The efficacy analysis set comprised subjects who have received at least 1 dose of theIMP, and from whom MADRS total scores have been obtained at baseline and at least 1 time point after initiation of the treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| New Subjects | Mean Changes From Baseline in Clinical Global Impression-Severity of Illness(CGI-S) at Week 52(LOCF) | -0.5 units on a scale | Standard Deviation 1.3 |
| Rollover Subjects | Mean Changes From Baseline in Clinical Global Impression-Severity of Illness(CGI-S) at Week 52(LOCF) | -0.5 units on a scale | Standard Deviation 1 |
Secondary
Mean Changes From Baseline in Hamiliton Depression Rating Scale(HAM-D) Item Total Scores at Week 52(LOCF)
The HAM-D was a clinician-rated scale which evaluated the level of depression. The HAM-D consists of 17 items such as depression mood, feeling of guilt, suicide, insomnia, work and activities, retardation, and so on. Each item was scored from 0 to 2, 3 or 4, with higher scores indicating worse condition. Summed subscales were combined to compute a total score. Total score ranges from 0 to 53 , with higher score indicating worse condition.
Time frame: Baseline and Week 52 (LOCF)
Population: The efficacy analysis set comprised subjects who have received at least 1 dose of theIMP, and from whom MADRS total scores have been obtained at baseline and at least 1 time point after initiation of the treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| New Subjects | Mean Changes From Baseline in Hamiliton Depression Rating Scale(HAM-D) Item Total Scores at Week 52(LOCF) | -2.2 units on a scale | Standard Deviation 8.3 |
| Rollover Subjects | Mean Changes From Baseline in Hamiliton Depression Rating Scale(HAM-D) Item Total Scores at Week 52(LOCF) | -4.1 units on a scale | Standard Deviation 6.6 |
Secondary
Mean Changes From Baseline in Montgomery Åsberg Depression Rating Scale(MADRS) Total Scores at Week 52(LOCF)
The MADRS was a clinician-rated scale which evaluated the level of depression.The MADRS consists of 10 items assessed 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.
Time frame: Baseline and Week 52(LOCF)
Population: The efficacy analysis set comprised subjects who have received at least 1 dose of the IMP, and from whom MADRS total scores have been obtained at baseline and at least 1 time point after initiation of the treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| New Subjects | Mean Changes From Baseline in Montgomery Åsberg Depression Rating Scale(MADRS) Total Scores at Week 52(LOCF) | -2.8 Units on a scale | Standard Error 10.4 |
| Rollover Subjects | Mean Changes From Baseline in Montgomery Åsberg Depression Rating Scale(MADRS) Total Scores at Week 52(LOCF) | -4.9 Units on a scale | Standard Error 9 |
Secondary
Mean Changes From Baseline in Sheehan Disability Scale (SDS) Scores at Week 52(LOCF)
SDS Scale was a patient-rated scale which assessed the degree of impairment for each of 3 items (work/school, social life, and family life/home responsibilities) on a 11-point scale ranging from 0 to 10. The mean SDS score was the mean of scores for 3 items. Higher scores indicate worse condition.
Time frame: Baseline and Week 52 (LOCF)
Population: The efficacy analysis set comprised subjects who have received at least 1 dose of theIMP, and from whom MADRS total scores have been obtained at baseline and at least 1 time point after initiation of the treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| New Subjects | Mean Changes From Baseline in Sheehan Disability Scale (SDS) Scores at Week 52(LOCF) | 0.43 score on a scale | Standard Deviation 2.48 |
| Rollover Subjects | Mean Changes From Baseline in Sheehan Disability Scale (SDS) Scores at Week 52(LOCF) | -0.61 score on a scale | Standard Deviation 2.35 |
Secondary
The Proportion of Subjects Who Score 1 or 2 on the Clinical Global Impression-Improvement(CGI-I) Scale at Week 52(LOCF)
The CGI-I Scale was clinician-rated scale which assessed the total improvement of the patient'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 indicate worse condition.
Time frame: Baseline and Week 52 (LOCF)
Population: The efficacy analysis set comprised subjects who have received at least 1 dose of theIMP, and from whom MADRS total scores have been obtained at baseline and at least 1 time point after initiation of the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| New Subjects | The Proportion of Subjects Who Score 1 or 2 on the Clinical Global Impression-Improvement(CGI-I) Scale at Week 52(LOCF) | 29.0 percentage of Participants |
| Rollover Subjects | The Proportion of Subjects Who Score 1 or 2 on the Clinical Global Impression-Improvement(CGI-I) Scale at Week 52(LOCF) | 37.0 percentage of Participants |