Major Depressive Disorder
Conditions
Brief summary
To evaluate the efficacy and safety of brexpiprazole as adjunctive treatment in elderly patients with Major Depressive Disorder (MDD)
Interventions
DRUGPlacebo
Once daily, tablets, orally
DRUGBrexpiprazole 1 mg
once daily dose, tablets, orally
DRUGBrexpiprazole 3 mg
once daily dose, tablets, orally
Sponsors
Otsuka Pharmaceutical Co., Ltd.
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient is an outpatient consulting a psychiatrist. * The patient has a recurrent Major Depressive Disorder diagnosed according to DSM-IV-TR™. The current Major Depressive Episode (MDE) should be confirmed using the Mini International Neuropsychiatric Interview (MINI). * The patient had at least one previous MDE before the age of 60 years. * The patient has a moderate to severe depression and an insufficient response to at least one and no more than three adequate antidepressants treatments. * The patient, if a woman, must have had her last natural menstruation ≥24 months prior to the Screening Visit. * The patient, if a man, agrees to protocol-defined use of effective contraception if his female partner is of childbearing potential.
Exclusion criteria
* The patient has any current psychiatric disorder or Axis I disorder (DSM-IV-TR™ criteria), established as the primary diagnosis, other than MDD. * The patient has a current Axis II (DSM-IV-TR™) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypical or histrionic personality disorder. * The patient has experienced/experiences hallucinations, delusions or any psychotic symptomatology in the current MDE. * The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria). * The patient, in the opinion of the investigator, or according to Columbia Suicide Severity Rating Scale (C-SSRS), is at significant risk of suicide. * The patient has had neuroleptic malignant syndrome. * The patient has any relevant medical history or current presence of systemic disease. * The patient has a neurodegenerative disorder. * The patient has, at the Screening Visit an abnormal ECG that is, in the investigator's opinion, clinically significant. * The patient has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for \>5 years prior to the first dose of IMP. * The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason. Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Randomisation in Depressive Symptoms During the Randomised Treatment | From randomisation to end of treatment (week 20) | Montgomery and Aasberg Depression Rating Scale (MADRS) total score |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Randomisation in Clinical Global Impression During the Randomised Treatment | From randomisation to end of treatment (week 20) | Clinical Global Impression - Severity of illness (CGI-S) score |
| Change From Randomisation in Functionality Assessed by SDS During the Randomised Treatment | From randomisation to end of treatment (week 20) | Sheehan Disability Scale (SDS) total score |
| Change From Randomisation in Social Adaptation During the Randomised Treatment | From randomisation to end of treatment (week 20) | Social Adaptation Self-evaluation Scale (SASS) total score |
| Response During the Randomised Treatment | From randomisation to end of treatment (week 20) | Based on a pre-specified decrease in MADRS total score |
| Number of Adverse Events | From randomisation to follow-up (week 24) | 15 patients were enrolled to Period 2; only 3 patients completed due to study termination |
| Remission During the Randomised Treatment | From randomisation to end of treatment (week 20) | Based on a pre-specified MADRS total score |
| Sustained Remission During the Randomised Treatment | From randomisation to end of treatment (week 20) | Based on a pre-specified MADRS total score |
| Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | From randomisation to end of treatment (week 20) | The Columbia Suicide Severity Rating Scale (eC-SSRS) is a semi-structured interview developed to systematically assess suicidal ideation and behaviour of patients participating in a clinical study. The C-SSRS has 5 questions addressing suicidal ideation, 5 sub-questions assessing the intensity of ideation, and 4 questions addressing suicidal behaviour. |
| Sustained Response During the Randomised Treatment | From randomisation to end of treatment (week 20) | Based on a pre-specified decrease in MADRS total score |
Countries
United States
Participant flow
Recruitment details
129 patients were enrolled in the study and 128 patients received open-label treatment with one of six commercially available antidepressant antidepressant treatments (ADT) together with double-blind study treatment. Only 15 patients were randomized to Period 2 before the study was terminated; 47 patients entered Period 3.
Participants by arm
| Arm | Count |
|---|---|
| Period 2 Placebo and ADT Placebo adjunct to open-label treatment with a commercially available antidepressant (ADT)
Placebo: Once daily, tablets, orally | 6 |
| Period 2 Brexpiprazole 1 mg and ADT Brexpiprazole 1 mg adjunct to open-label treatment with a commercially available antidepressant (ADT)
Brexpiprazole: 1 mg once daily, tablets, orally | 3 |
| Period 2 Brexpiprazole 3 mg and ADT Brexpiprazole 3 mg adjunct to open-label treatment with a commercially available antidepressant (ADT)
Brexpiprazole: 3 mg once daily, tablets, orally | 6 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period 1 | Administrative reasons | 76 | 0 | 0 | 0 | 0 |
| Period 1 | Adverse Event | 9 | 0 | 0 | 0 | 0 |
| Period 1 | Other | 10 | 0 | 0 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 6 | 0 | 0 | 0 | 0 |
| Period 1 | Withdrawal of consent before treatment | 1 | 0 | 0 | 0 | 0 |
| Period 2 | Administrative or other reasons | 0 | 5 | 2 | 4 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 0 | 1 | 0 |
| Period 3 | Administrative reasons | 0 | 0 | 0 | 0 | 20 |
| Period 3 | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Period 3 | Other | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Period 2 Placebo and ADT | Period 2 Brexpiprazole 1 mg and ADT | Period 2 Brexpiprazole 3 mg and ADT | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 3 Participants | 6 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 2 / 3 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 | 0 / 6 |
Outcome results
Primary
Change From Randomisation in Depressive Symptoms During the Randomised Treatment
Montgomery and Aasberg Depression Rating Scale (MADRS) total score
Time frame: From randomisation to end of treatment (week 20)
Population: Only 3 patients completed study Period 2. A total of 129 patients were enrolled when the study was terminated (Planned: 1334 patients). The limited number of enrolled patients would result in insufficient data for analyses, therefore, no data were collected
Secondary
Change From Randomisation in Clinical Global Impression During the Randomised Treatment
Clinical Global Impression - Severity of illness (CGI-S) score
Time frame: From randomisation to end of treatment (week 20)
Population: Only 3 patients completed study Period 2. A total of 129 patients were enrolled when the study was terminated (Planned: 1334 patients). The limited number of enrolled patients would result in insufficient data for analyses, therefore, no data were collected
Secondary
Change From Randomisation in Functionality Assessed by SDS During the Randomised Treatment
Sheehan Disability Scale (SDS) total score
Time frame: From randomisation to end of treatment (week 20)
Population: Only 3 patients completed study Period 2. A total of 129 patients were enrolled when the study was terminated (Planned: 1334 patients). The limited number of enrolled patients would result in insufficient data for analyses, therefore, no data were collected
Secondary
Change From Randomisation in Social Adaptation During the Randomised Treatment
Social Adaptation Self-evaluation Scale (SASS) total score
Time frame: From randomisation to end of treatment (week 20)
Population: Only 3 patients completed study Period 2. A total of 129 patients were enrolled when the study was terminated (Planned: 1334 patients). The limited number of enrolled patients would result in insufficient data for analyses, therefore, no data were collected
Secondary
Number of Adverse Events
15 patients were enrolled to Period 2; only 3 patients completed due to study termination
Time frame: From randomisation to follow-up (week 24)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period 2 Placebo and ADT | Number of Adverse Events | 3 Adverse events |
| Period 2 Brexpiprazole 1 mg and ADT | Number of Adverse Events | 5 Adverse events |
| Period 2 Brexpiprazole 3 mg and ADT | Number of Adverse Events | 2 Adverse events |
Secondary
Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
The Columbia Suicide Severity Rating Scale (eC-SSRS) is a semi-structured interview developed to systematically assess suicidal ideation and behaviour of patients participating in a clinical study. The C-SSRS has 5 questions addressing suicidal ideation, 5 sub-questions assessing the intensity of ideation, and 4 questions addressing suicidal behaviour.
Time frame: From randomisation to end of treatment (week 20)
Population: 15 patients were enrolled to Period 2, only 3 patients completed due to study termination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Period 2 Placebo and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | No suicidal ideation or behaviour | 6 participants |
| Period 2 Placebo and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Any non-suicidal self-injurious behavior | 0 participants |
| Period 2 Placebo and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Suicidal Ideation | 0 participants |
| Period 2 Placebo and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Preparatory action towards imminent suicidal behav | 0 participants |
| Period 2 Placebo and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Not fatal suicide attempt | 0 participants |
| Period 2 Placebo and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Completed suicide | 0 participants |
| Period 2 Brexpiprazole 1 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Completed suicide | 0 participants |
| Period 2 Brexpiprazole 1 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | No suicidal ideation or behaviour | 3 participants |
| Period 2 Brexpiprazole 1 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Preparatory action towards imminent suicidal behav | 0 participants |
| Period 2 Brexpiprazole 1 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Not fatal suicide attempt | 0 participants |
| Period 2 Brexpiprazole 1 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Any non-suicidal self-injurious behavior | 0 participants |
| Period 2 Brexpiprazole 1 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Suicidal Ideation | 0 participants |
| Period 2 Brexpiprazole 3 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Any non-suicidal self-injurious behavior | 0 participants |
| Period 2 Brexpiprazole 3 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Suicidal Ideation | 2 participants |
| Period 2 Brexpiprazole 3 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Completed suicide | 0 participants |
| Period 2 Brexpiprazole 3 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Preparatory action towards imminent suicidal behav | 0 participants |
| Period 2 Brexpiprazole 3 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | No suicidal ideation or behaviour | 4 participants |
| Period 2 Brexpiprazole 3 mg and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Not fatal suicide attempt | 0 participants |
Secondary
Remission During the Randomised Treatment
Based on a pre-specified MADRS total score
Time frame: From randomisation to end of treatment (week 20)
Population: Only 3 patients completed study Period 2. A total of 129 patients were enrolled when the study was terminated (Planned: 1334 patients). The limited number of enrolled patients would result in insufficient data for analyses, therefore, no data were collected
Secondary
Response During the Randomised Treatment
Based on a pre-specified decrease in MADRS total score
Time frame: From randomisation to end of treatment (week 20)
Population: Only 3 patients completed study Period 2. A total of 129 patients were enrolled when the study was terminated (Planned: 1334 patients). The limited number of enrolled patients would result in insufficient data for analyses, therefore, no data were collected
Secondary
Sustained Remission During the Randomised Treatment
Based on a pre-specified MADRS total score
Time frame: From randomisation to end of treatment (week 20)
Population: Only 3 patients completed study Period 2. A total of 129 patients were enrolled when the study was terminated (Planned: 1334 patients). The limited number of enrolled patients would result in insufficient data for analyses, therefore, no data were collected
Secondary
Sustained Response During the Randomised Treatment
Based on a pre-specified decrease in MADRS total score
Time frame: From randomisation to end of treatment (week 20)
Population: Only 3 patients completed study Period 2. A total of 129 patients were enrolled when the study was terminated (Planned: 1334 patients). The limited number of enrolled patients would result in insufficient data for analyses, therefore, no data were collected