Major Depressive Disorder
Conditions
Brief summary
To evaluate the long-term safety and tolerability of brexpiprazole as adjunctive treatment in patients with Major Depressive Disorder (MDD)
Detailed description
This extension safety study was terminated early because one of the lead-in studies (14571A) in elderly was terminated and because the Sponsor considered that sufficient long-term safety data has already been collected in the development programme in the population aged 18-65 yrs.
Interventions
DRUGBrexpiprazole
1, 2, or 3 mg/day, once daily dose, tablets, orally. Uptitration in weekly steps from 0.5 mg/day (patients ≥65) or 1 mg/day (patients 18-64 years)
Sponsors
Otsuka Pharmaceutical Co., Ltd.
H. Lundbeck A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient is judged to benefit from adjunctive treatment with brexpiprazole according to the clinical opinion of the investigator. * The patient had MDD at entry in lead-in brexpiprazole studies, NCT01838681 / 14570A or NCT01837797 / 14571A, diagnosed according to DSM-IV-TR™. * The patient agrees to protocol-defined use of effective contraception.
Exclusion criteria
* The patient has a disease or takes medication that could, in the investigator's opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with the conduct or interpretation of the study. * The patient has been diagnosed with a psychiatric disorder other than MDD during the lead-in studies NCT01838681 / 14570A or NCT01837797 / 14571A. * The patient, in the opinion of the investigator or according to C-SSRS, is at significant risk of suicide. * The patient has any relevant medical history or current presence of systemic disease. * The patient has, at the Baseline Visit an abnormal ECG that is, in the investigator's opinion, clinically significant. * The patient has a moderate or severe ongoing adverse event related to study medication from the lead-in studies considered of potential safety risk by the investigator. * 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 |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events | From baseline to Week 52 | Number of participants with Treatment-Emergent Adverse Events |
| Number of Withdrawals | From baseline to Week 52 | Number of withdrawals |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients in Remission | From baseline to Week 52 | 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 baseline to Week 52 | 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. The electronic C-SSRS (eC-SSRS) is a patient-rated electronic version using interactive voice response technology. A structured CSSRS script of standardised questions, follow-up prompts, error-handling and scoring conventions is used for administration. |
| Change in Health-related Quality of Life | From baseline to Week 52 | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-(SF)) total score |
| Change in Clinical Global Impression | From baseline to Week 52 | Clinical Global Impression - Severity of illness (CGI-S) score |
| Change in Depressive Symptoms | From baseline to Week 52 | The Montgomery and Aasberg Depression Rating Scale (MADRS) total score |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole and ADT Brexpiprazole adjunct to open-label treatment with a commercially available antidepressant (ADT)
Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative or other reasons | 23 |
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Non-compliance with IMP | 1 |
Baseline characteristics
| Characteristic | Brexpiprazole and ADT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 23 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 66.12 years STANDARD_DEVIATION 10.03 |
| Region of Enrollment Estonia | 3 participants |
| Region of Enrollment Finland | 2 participants |
| Region of Enrollment Germany | 2 participants |
| Region of Enrollment Slovakia | 2 participants |
| Region of Enrollment Sweden | 2 participants |
| Region of Enrollment United Kingdom | 1 participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 26 |
| serious Total, serious adverse events | 0 / 26 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events
Number of participants with Treatment-Emergent Adverse Events
Time frame: From baseline to Week 52
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole and ADT | Number of Participants With Treatment-Emergent Adverse Events | 28 participants |
Primary
Number of Withdrawals
Number of withdrawals
Time frame: From baseline to Week 52
Population: 26 patients were withdrawn; the reason for withdrawal was not poor tolerability, but mainly (23 patients) because the study was terminated. Please see withdrawn reasons in the participant flow section for the other reasons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole and ADT | Number of Withdrawals | 26 participants |
Secondary
Change in Clinical Global Impression
Clinical Global Impression - Severity of illness (CGI-S) score
Time frame: From baseline to Week 52
Population: No patients completed the study. Only 26 patients were enrolled at prematurely study termination (Planned: 1184 patients). No data were collected because none of the 26 patients that were enrolled completed the study because of early termination.
Secondary
Change in Depressive Symptoms
The Montgomery and Aasberg Depression Rating Scale (MADRS) total score
Time frame: From baseline to Week 52
Population: None of the patients completed the study. A total of 26 patients were enrolled when the study was prematurely terminated(Planned: 1184 patients). No data were collected because none of the 26 patients that were enrolled completed the study because of early termination.
Secondary
Change in Health-related Quality of Life
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-(SF)) total score
Time frame: From baseline to Week 52
Population: No patients completed the study. Only 26 patients were enrolled at prematurely study termination (Planned: 1184 patients). No data were collected because none of the 26 patients that were enrolled completed the study because of early termination.
Secondary
Change in Health-related Quality of Life
The EuroQoL 5 Dimensions 5L version (EQ-5D-5L) Visual Analogue Scale (VAS) is a patient-reported assessment designed to measure the patient's wellbeing. It consists of 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety) and a visual analogue scale (VAS) of the overall health state. Each descriptive item is rated on a 5-point index ranging from 1 (no problems) to 5 (extreme problems) and a single summary index (from 0 to 1) can be calculated. The VAS ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time frame: Baseline and Week 52
Population: No patients completed the study. Only 26 patients were enrolled at prematurely study termination (Planned: 1184 patients). No data were collected because none of the 26 patients that were enrolled completed the study because of early termination.
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. The electronic C-SSRS (eC-SSRS) is a patient-rated electronic version using interactive voice response technology. A structured CSSRS script of standardised questions, follow-up prompts, error-handling and scoring conventions is used for administration.
Time frame: From baseline to Week 52
Population: all-patients treated set (APTS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brexpiprazole 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 | 25 participants |
| Brexpiprazole 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 |
| Brexpiprazole and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Suicidal Ideation | 1 participants |
| Brexpiprazole 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 | 0 participants |
| Brexpiprazole 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 |
| Brexpiprazole and ADT | Number of Patients With Risk of Suicidality Assessed Using the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | Completed suicide | 0 participants |
Secondary
Proportion of Patients in Remission
Based on a pre-specified MADRS total score
Time frame: From baseline to Week 52
Population: No patients completed the study. Only 26 patients were enrolled at prematurely study termination (Planned: 1184 patients). No data were collected because none of the 26 patients that were enrolled completed the study because of early termination.