Major Depressive Disorder
Conditions
Brief summary
To evaluate the efficacy and the safety of ASC-01 (aripiprazole/sertraline combination) compared to sertraline monotherapy in patients with major depressive disorders who have responded incompletely to sertraline monotherapy.
Interventions
DRUGASC-01
DRUGPlacebo
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Patients who are either inpatients or outpatients. * Patients who are able to understand necessary information for giving consent to undergo examinations, observations, and evaluations specified in this clinical protocol, and who are able to give written consent based on a full understanding of the trial. * Patients who have been given a diagnosis of Major Depressive Disorder, Single Episode or Major Depressive Disorder, Recurrent according to the DSM-5 and who have a current episode of major depression that has been continuing for at least 8 weeks * Patients with a HAM-D 17 total score of 18 or more at the Screening Period evaluation
Exclusion criteria
* Female patients of childbearing potential who wish to become pregnant during the trial period or within 4 weeks after completion or discontinuation of the trial * Pregnant or breast-feeding female patients, or female patients who may be pregnant * Patients judged to be intolerant to all antidepressant (including drugs not used for their current episodes of major depression) based on their treatment history * Patients who have had electroconvulsive therapy * Patients who have enrolled in a clinical trial of other drugs or medical devices within 1 month before the time of informed consent * Patients who have a medical history suggesting a risk of developing serious adverse events or symptoms that may hinder efficacy/safety evaluation (eg, symptoms of fibromyalgia, or premenstrual syndrome etc that overlap with depressive symptoms) * Patients with complications or a history of diabetes mellitus, or patients who have been judged to be diabetic * fasting blood glucose level ≥ 126 mg/dL * 2-hour glucose level in 75-g oral glucose tolerance test (OGTT) ≥ 200 mg/dL * non-fasting blood glucose level ≥ 200 mg/dL * HbA1c \[NGSP level\] ≥ 6.5% * Patients who are undergoing treatment for thyroid disease (except for patients whose disease has been stabilized with drug therapy for 3 months or longer before the time of informed consent) * Patients who have a history of neuroleptic malignant syndrome or serotonin syndrome * Patients who have a history of seizure disorder (eg, epilepsy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF]) | The MADRS is a clinician-rated scale which evaluates the level of depression. The MADRS consists 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 is scored from 0 to 6, with higher scores indicating worse condition.Summed subscales are combined to compute a total score. Total score ranges from 0 to 60, with higher score indicating worse condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Montgomery-Åsberg Depression Rating Scale (MADRS) Response Rate | 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF]) | The MADRS is a clinician-rated scale which evaluates the level of depression. The MADRS consists 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 is scored from 0 to 6, with higher scores indicating worse condition. MADRS Response Rate is the percentage of subjects who achieved a decrease in the MADRS total score by 50% or more. |
| The Montgomery-Åsberg Depression Rating Scale (MADRS) Remission Rate | 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF]) | The MADRS is a clinician-rated scale which evaluates the level of depression. The MADRS consists 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 is scored from 0 to 6, with higher scores indicating worse condition. MADRS Remission Rate is the percentage of subjects who achieved a decrease in the MADRS total score by 50% or more and whose MADRS total score is 10 points or less. |
| The Clinical Global Impression - Improvement (CGI-I) Improvement Rate | 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF]) | The CGI-I Scale is a clinician-rated scale which assesses 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. CGI-I Improvement Rate is the percentage of subjects whose CGI-I score is 1 or 2. |
| The Mean Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) | 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF]) | The CGI-S Scale is a clinician-rated scale which assesses 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. |
| The Mean Change From Baseline in the Hamilton Depression Rating Scale 17 (HAM-D17) Total Score | 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF]) | The HAM-D is a clinician-rated scale which evaluates 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 is scored from 0 to 2, 3 or 4, with higher scores indicating worse condition. Summed subscales are combined to compute a total score. Total score ranges from 0 to 52, with higher score indicating worse condition. |
| The Mean Change From Baseline in the Social Adaptation Self-evaluation Scale (SASS) Total Score | 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF]) | The SASS is a self-rating scale which assesses the social motivation and behavior in participants with depression. The SASS consists of 21 items covering the different aspects of social interactions, global social attitude, and self-perception. Each item is scored from 0 to 3, with higher scores indicating better condition. |
| The Mean Change From Baseline in the Apathy Scale (AS) Total Score | 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF]) | The AS consists of 14 items. Items 1-8 are scored as follows: 3= Not at all, 2= Slightly, 1= Some, 0= A lot. Items 9-14 are scored as follows: 0= Not at all, 1= Slightly, 2= Some, 3= A lot. Total score ranges from 0-42, with higher score indicating worse condition. |
| The Mean Change From Baseline in the Self-rating Version of Montgomery-Åsberg Depression Rating Scale (MADRS-S) Total Score | 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF]) | The MADRS-S is a patient-reported scale based on MADRS, administered to evaluate the level of depression. This scale consists of 9 items assessing patients' mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored from 0 to 3, with higher scores indicating worse condition. Summed subscales are combined to compute a total score. Total score ranges from 0 to 27, with higher score indicating worse condition. |
Countries
Australia, Japan, Malaysia, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ASC-01 * Formulation A: ASC-01 (aripiprazole/sertraline combination) 3 mg/100 mg tablet
* Formulation B: ASC-01 (aripiprazole/sertraline combination) 6 mg/100 mg tablet
* Formulation C: ASC-01 (aripiprazole/sertraline combination) 9 mg/100 mg tablet
* Formulation D: ASC-01 (aripiprazole/sertraline combination) 12 mg/100 mg tablet Formulation A or, B, C, or D was orally administered once daily. For Week 1, Formulation A was administered after which administration was conducted according to the dose-increase criteria. The formulation was fixed from Week 5 to Week 6. | 208 |
| Placebo The dose of 0mg/100mg (Placebo/Sertraline Combination ）will be orally administered once daily. | 203 |
| Total | 411 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Subject met withdrawal criteria | 2 | 5 |
| Overall Study | Withdrawal by Subject | 4 | 10 |
Baseline characteristics
| Characteristic | ASC-01 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 208 Participants | 203 Participants | 411 Participants |
| Age, Continuous | 38.3 years STANDARD_DEVIATION 11.8 | 39.5 years STANDARD_DEVIATION 11.8 | 38.9 years STANDARD_DEVIATION 11.8 |
| Region of Enrollment Australia | 2 participants | 4 participants | 6 participants |
| Region of Enrollment Japan | 157 participants | 142 participants | 299 participants |
| Region of Enrollment Malaysia | 6 participants | 5 participants | 11 participants |
| Region of Enrollment South Korea | 36 participants | 42 participants | 78 participants |
| Region of Enrollment Taiwan | 7 participants | 10 participants | 17 participants |
| Sex: Female, Male Female | 79 Participants | 72 Participants | 151 Participants |
| Sex: Female, Male Male | 129 Participants | 131 Participants | 260 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 209 | 0 / 203 |
| other Total, other adverse events | 128 / 209 | 107 / 203 |
| serious Total, serious adverse events | 0 / 209 | 2 / 203 |
Outcome results
Primary
The Mean Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
The MADRS is a clinician-rated scale which evaluates the level of depression. The MADRS consists 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 is scored from 0 to 6, with higher scores indicating worse condition.Summed subscales are combined to compute a total score. Total score ranges from 0 to 60, with higher score indicating worse condition.
Time frame: 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASC-01 | The Mean Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -9.2 units on a scale | Standard Error 0.5 |
| Placebo | The Mean Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | -7.2 units on a scale | Standard Error 0.5 |
Secondary
The Clinical Global Impression - Improvement (CGI-I) Improvement Rate
The CGI-I Scale is a clinician-rated scale which assesses 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. CGI-I Improvement Rate is the percentage of subjects whose CGI-I score is 1 or 2.
Time frame: 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASC-01 | The Clinical Global Impression - Improvement (CGI-I) Improvement Rate | 46.2 percentage of participants |
| Placebo | The Clinical Global Impression - Improvement (CGI-I) Improvement Rate | 34.5 percentage of participants |
Secondary
The Mean Change From Baseline in the Apathy Scale (AS) Total Score
The AS consists of 14 items. Items 1-8 are scored as follows: 3= Not at all, 2= Slightly, 1= Some, 0= A lot. Items 9-14 are scored as follows: 0= Not at all, 1= Slightly, 2= Some, 3= A lot. Total score ranges from 0-42, with higher score indicating worse condition.
Time frame: 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASC-01 | The Mean Change From Baseline in the Apathy Scale (AS) Total Score | -3.3 units on a scale | Standard Error 0.4 |
| Placebo | The Mean Change From Baseline in the Apathy Scale (AS) Total Score | -1.1 units on a scale | Standard Error 0.4 |
Secondary
The Mean Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S)
The CGI-S Scale is a clinician-rated scale which assesses 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: 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASC-01 | The Mean Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) | -1.0 units on a scale | Standard Error 0.1 |
| Placebo | The Mean Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) | -0.8 units on a scale | Standard Error 0.1 |
Secondary
The Mean Change From Baseline in the Hamilton Depression Rating Scale 17 (HAM-D17) Total Score
The HAM-D is a clinician-rated scale which evaluates 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 is scored from 0 to 2, 3 or 4, with higher scores indicating worse condition. Summed subscales are combined to compute a total score. Total score ranges from 0 to 52, with higher score indicating worse condition.
Time frame: 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASC-01 | The Mean Change From Baseline in the Hamilton Depression Rating Scale 17 (HAM-D17) Total Score | -6.8 units on a scale | Standard Error 0.4 |
| Placebo | The Mean Change From Baseline in the Hamilton Depression Rating Scale 17 (HAM-D17) Total Score | -5.6 units on a scale | Standard Error 0.4 |
Secondary
The Mean Change From Baseline in the Self-rating Version of Montgomery-Åsberg Depression Rating Scale (MADRS-S) Total Score
The MADRS-S is a patient-reported scale based on MADRS, administered to evaluate the level of depression. This scale consists of 9 items assessing patients' mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored from 0 to 3, with higher scores indicating worse condition. Summed subscales are combined to compute a total score. Total score ranges from 0 to 27, with higher score indicating worse condition.
Time frame: 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASC-01 | The Mean Change From Baseline in the Self-rating Version of Montgomery-Åsberg Depression Rating Scale (MADRS-S) Total Score | -2.85 units on a scale | Standard Error 0.22 |
| Placebo | The Mean Change From Baseline in the Self-rating Version of Montgomery-Åsberg Depression Rating Scale (MADRS-S) Total Score | -1.86 units on a scale | Standard Error 0.23 |
Secondary
The Mean Change From Baseline in the Social Adaptation Self-evaluation Scale (SASS) Total Score
The SASS is a self-rating scale which assesses the social motivation and behavior in participants with depression. The SASS consists of 21 items covering the different aspects of social interactions, global social attitude, and self-perception. Each item is scored from 0 to 3, with higher scores indicating better condition.
Time frame: 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASC-01 | The Mean Change From Baseline in the Social Adaptation Self-evaluation Scale (SASS) Total Score | 3.7 units on a scale | Standard Error 0.3 |
| Placebo | The Mean Change From Baseline in the Social Adaptation Self-evaluation Scale (SASS) Total Score | 1.5 units on a scale | Standard Error 0.3 |
Secondary
The Montgomery-Åsberg Depression Rating Scale (MADRS) Remission Rate
The MADRS is a clinician-rated scale which evaluates the level of depression. The MADRS consists 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 is scored from 0 to 6, with higher scores indicating worse condition. MADRS Remission Rate is the percentage of subjects who achieved a decrease in the MADRS total score by 50% or more and whose MADRS total score is 10 points or less.
Time frame: 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASC-01 | The Montgomery-Åsberg Depression Rating Scale (MADRS) Remission Rate | 29.3 percentage of participants |
| Placebo | The Montgomery-Åsberg Depression Rating Scale (MADRS) Remission Rate | 20.2 percentage of participants |
Secondary
The Montgomery-Åsberg Depression Rating Scale (MADRS) Response Rate
The MADRS is a clinician-rated scale which evaluates the level of depression. The MADRS consists 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 is scored from 0 to 6, with higher scores indicating worse condition. MADRS Response Rate is the percentage of subjects who achieved a decrease in the MADRS total score by 50% or more.
Time frame: 8 weeks after the start of the sertraline treatment period (Baseline), 6 weeks after the start of the double-blind period (Last Observation Carried Forward [LOCF])
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASC-01 | The Montgomery-Åsberg Depression Rating Scale (MADRS) Response Rate | 37.5 percentage of participants |
| Placebo | The Montgomery-Åsberg Depression Rating Scale (MADRS) Response Rate | 25.6 percentage of participants |