Major Depressive Disorder
Conditions
Keywords
MDD, Depression, Brexpiprazole
Brief summary
The clinical trial will investigate the effect of brexpiprazole on the concept of life engagement in participants with Major Depressive Disorder (MDD) with a current depressive episode.
Detailed description
This is a phase 4, multicenter, open-label, flexible dose trial designed to assess the effects of brexpiprazole (flexible dose; 0.5 to 2 milligrams \[mg\], once daily \[QD\]) as adjunctive therapy to antidepressant therapy (ADT) on life engagement in participants with MDD. This trial is being conducted in line with the Canadian Product Monograph.
Interventions
DRUGBrexpiprazole
Oral brexpiprazole tablets as adjunctive therapy to ADT
Sponsors
Lundbeck Canada Inc.
Otsuka Canada Pharmaceutical Inc.
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female participants (outpatients) between the regional age of majority (18 or 19 years of age) to 65 years of age, inclusive, at the time of informed consent. * Primary diagnosis of MDD and in a current non-psychotic major depressive episode (MDE) as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, who have been outpatients for at least 4 weeks, and have an inadequate response, per investigator judgment, to 1 or 2 adequate treatments of ADTs in their current MDE, including current ADT. * Participants with a Patient Health Questionnaire 9-item scale (PHQ-9) ≥ 15 at the screening and baseline visits, if separate.
Exclusion criteria
* Participants currently or previously treated with brexpiprazole including participants who received brexpiprazole in any prior clinical trial. * Participants with a concurrent DSM-5 diagnosis of the following will be excluded: * Schizophrenia or schizoaffective disorder * Bipolar I or bipolar II disorder * Post-traumatic stress disorder * Dementia * Eating disorder * Borderline personality disorder * Antisocial personality disorder * Participants with a suicidality score of 3 based on Inventory of Depressive Symptomatology Self-Report (IDS-SR) suicidality item 18 or participants who, in the opinion of the investigator, presents a serious risk of suicide.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in IDS-SR-10 Engagement | Baseline to Week 8 | The IDS-SR-10 engagement consist of selected 10 item scores, including the following 10 items (clinician-selected): item 8 - Response of your mood to good or desired events, item 15 - Concentration/decision making, item 16 - View of myself, item 17 - View of my future, item 19 - General interest, item 20 - Energy level, item 21 - Capacity for pleasure or enjoyment (excluding sex), item 22 - Interest in sex (interest rated, not activity), item 23 - Feeling slowed down, and item 29- Interpersonal sensitivity. All the 10 items are rated on a 0 (best) to 3 (worst) scale. IDS-SR-10 engagement total score ranges from 0 (best) to 30 (worst). A negative change from baseline indicated improvement. Least square (LS) mean was calculated using a mixed model repeated measure (MMRM) analysis. |
| Change From Baseline in IDS-SR Total Score | Baseline to Week 8 | The IDS-SR is a 30-item self-report measure that was used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorder (MDD). Each item on the IDS-SR scale was rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. IDS-SR total score is the sum of ratings of 28 item scores with the total score ranging from 0 (best) to 84 (worst). Under item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. A negative change from baseline indicated improvement. LS mean was calculated using a MMRM analysis. |
Countries
Canada
Participant flow
Recruitment details
Participants took part in this study at 15 investigative sites in Canada from 01 April 2021 to 27 May 2022.
Pre-assignment details
A total of 157 participants were screened of which 122 participants were enrolled and 120 participants were treated in the study.
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole Participants received brexpiprazole as a flexible dose; 0.5 mg to 2 mg, PO, QD, and continued on the stable dose of ADT up to 8 weeks. | 122 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Failure to Meet Continuation Criteria | 1 |
| Overall Study | Protocol Deviation | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Brexpiprazole |
|---|---|
| Age, Continuous | 43.0 years STANDARD_DEVIATION 13.1 |
| IDS-SR-10 Engagement | 16.1 score on a scale STANDARD_DEVIATION 4.7 |
| IDS-SR Total Score | 41.3 score on a scale STANDARD_DEVIATION 9.8 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 117 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 3 Participants |
| Race/Ethnicity, Customized Race Asian | 7 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants |
| Race/Ethnicity, Customized Race White | 111 Participants |
| Sex: Female, Male Female | 79 Participants |
| Sex: Female, Male Male | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 120 |
| other Total, other adverse events | 45 / 120 |
| serious Total, serious adverse events | 0 / 120 |
Outcome results
Primary
Change From Baseline in IDS-SR-10 Engagement
The IDS-SR-10 engagement consist of selected 10 item scores, including the following 10 items (clinician-selected): item 8 - Response of your mood to good or desired events, item 15 - Concentration/decision making, item 16 - View of myself, item 17 - View of my future, item 19 - General interest, item 20 - Energy level, item 21 - Capacity for pleasure or enjoyment (excluding sex), item 22 - Interest in sex (interest rated, not activity), item 23 - Feeling slowed down, and item 29- Interpersonal sensitivity. All the 10 items are rated on a 0 (best) to 3 (worst) scale. IDS-SR-10 engagement total score ranges from 0 (best) to 30 (worst). A negative change from baseline indicated improvement. Least square (LS) mean was calculated using a mixed model repeated measure (MMRM) analysis.
Time frame: Baseline to Week 8
Population: The Efficacy Analysis Set included all participants who had a baseline value and at least one post-baseline efficacy evaluation for IDS-SR total score and IDS-SR-10-engagement during the open label treatment phase. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole | Change From Baseline in IDS-SR-10 Engagement | -8.11 score on a scale | Standard Error 0.62 |
p-value: <0.0001MMRM
Primary
Change From Baseline in IDS-SR Total Score
The IDS-SR is a 30-item self-report measure that was used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorder (MDD). Each item on the IDS-SR scale was rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. IDS-SR total score is the sum of ratings of 28 item scores with the total score ranging from 0 (best) to 84 (worst). Under item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. A negative change from baseline indicated improvement. LS mean was calculated using a MMRM analysis.
Time frame: Baseline to Week 8
Population: The Efficacy Analysis included all participants who had a baseline value and at least one post-baseline efficacy evaluation for IDS-SR total score and IDS-SR-10-engagement during the open label treatment phase. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole | Change From Baseline in IDS-SR Total Score | -17.38 score on a scale | Standard Error 1.36 |
p-value: <0.0001MMRM