Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Adjunctive Treatment
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of TS-121 as an adjunctive treatment for patients with major depressive disorder with an inadequate response to current antidepressant Treatment (SSRI, SNRI or bupropion).
Interventions
DRUGTS-121 10 mg
Orally taken once daily
DRUGTS-121 50 mg
Orally taken once daily
DRUGPlacebo
Orally taken once daily
Sponsors
Taisho Pharmaceutical R&D Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adult males and females between 18 and 65 years of age inclusive (at time of initial informed consent) 2. Patients with a current diagnosis of MDD by DSM-5, confirmed through a structured interview using MINI 3. Patients who receive the same antidepressant (SSRI, SNRI or bupropion monotherapy) for at least 6 weeks of continuous treatment with at least 4 weeks on a fixed dose 4. Patients who willing to remain on the same primary SSRI, SNRI or bupropion and fixed dose throughout the course of the study 5. Patients who meet the total score on the HAM-D as listed below 1. HAM-D ≥ 18 at Screening 2. HAM-D ≥ 18 at Baseline 6. Body Mass Index (BMI) ≥ 18 and ≤ 38 kg/m2
Exclusion criteria
1. Patients with inadequate response to ≥2 prior antidepressant treatments (not including current antidepressant) of at least 4 weeks duration each for the current episode 2. Patients whose current depressive episode is diagnosed with psychotic features, catatonic features, post-partum (primary onset), or is secondary to a general medical disorder 3. Patients with a diagnosis of any of the following DSM-5 class disorders 1. Schizophrenia spectrum and other psychotic disorders 2. Bipolar and related disorders 3. Anxiety disorders \[Co-morbid GAD and SAD will be allowed in the study if the primary diagnosis is MDD, and if in the opinion of the investigator, the comorbid anxiety is not likely to interfere with the subject's ability to participate in the trial or affect study outcome\] 4. Obsessive-compulsive and related disorders 5. Trauma- and Stressor-related disorders 4. Patients who received electroconvulsive therapy (ECT) within 12 months of Screening, received more than one course of ECT in their lifetime or plan to receive ECT during the study 5. Patients who received repetitive transcranial magnetic stimulation (rTMS) within 12 months of Screening or plan to receive rTMS during the study 6. Patients who plan to initiate or terminate cognitive or behavioral psychotherapy or alter the frequency of ongoing therapy during this study 7. Patients who have attempted suicide within the past 6 months 8. Patients with history or presence of intellectual disability, pervasive developmental disorder, cognitive disorder, neurodegenerative disorder, or brain injury 9. Patients with any history or complication of convulsive disorder 10. Patients who are undergoing treatment with psychotropic medications, benzodiazepines, metyrapone, lithium and/or corticosteroids 11. Patients who are taking moderate to strong CYP3A4 inhibitors/inducers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) | 6 weeks | The MADRS is a clinician-rated scale to assess depressive symptoms which consists from 10 items. The time frame for this scale is the past 7 days. Each item is scored on 7-point scale (0 \[absence of symptoms\] to 6 \[severe\]). The total score is the sum of 10 items and can take range from 0 to 60. A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Anxiety Scale (HAM-A) | 6 weeks | The HAM-A is a clinician-rated scale to assess anxiety symptoms which consists from 14 items. The time frame for this scale is the past 7 days. Each item is scored on 5-point scale (0 \[absence of symptoms\] to 4 \[severe\]). The total score is the sum of 14 items and can take range from 0 to 56. A negative change from baseline indicates improvement. |
| Symptoms of Depression Questionnaire (SDQ) | 6 weeks | The SDQ is a self-rated scale to assess the severity of symptoms across several subtypes of depression which consists from 44 items. The time frame for this scale is the past 7 days. Each item is scored on 6-point scale (1 \[better than normal\] to 6 \[severe\]). The total score is the sum of 44 items and can take range from 44 to 264. A negative change from baseline indicates improvement. |
| Clinical Global Impression-Severity (CGI-S) | 6 weeks | The CGI-S is a clinician-rated scale to assess the severity of the disorder. The time frame for this scale is the past 7 days. The score ranges from 1 (Normal, not ill at all) to 7 (Among the most extremely ill patients). |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 6 weeks | Percentage of MADRS responders (≥ 50% reduction in total score) at Week 6 |
| Clinical Global Impression-Improvement (CGI-I) | 6 weeks | Percentage of CGI-I improvers (Very much improved or Much improved) at Week 6 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TS-121 10mg TS-121 10 mg: Orally taken once daily | 16 |
| TS-121 50mg TS-121 50 mg: Orally taken once daily | 16 |
| Placebo Placebo: Orally taken once daily | 18 |
| Total | 50 |
Baseline characteristics
| Characteristic | TS-121 10mg | TS-121 50mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 12.62 | 44.8 years STANDARD_DEVIATION 12.93 | 45.8 years STANDARD_DEVIATION 11.09 | 45.1 years STANDARD_DEVIATION 11.95 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 4 Participants | 3 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 10 Participants | 12 Participants | 29 Participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 12 Participants | 33 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 18 |
| other Total, other adverse events | 7 / 16 | 7 / 16 | 8 / 18 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 18 |
Outcome results
Primary
Montgomery-Asberg Depression Rating Scale (MADRS)
The MADRS is a clinician-rated scale to assess depressive symptoms which consists from 10 items. The time frame for this scale is the past 7 days. Each item is scored on 7-point scale (0 \[absence of symptoms\] to 6 \[severe\]). The total score is the sum of 10 items and can take range from 0 to 60. A negative change from baseline indicates improvement.
Time frame: 6 weeks
Population: Participants who did not receive at least one dose of investigational product or did not have at least one post-dose assessments were not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TS-121 10mg | Montgomery-Asberg Depression Rating Scale (MADRS) | -9.0 score on a scale |
| TS-121 50mg | Montgomery-Asberg Depression Rating Scale (MADRS) | -9.0 score on a scale |
| Placebo | Montgomery-Asberg Depression Rating Scale (MADRS) | -6.4 score on a scale |
Secondary
Clinical Global Impression-Improvement (CGI-I)
Percentage of CGI-I improvers (Very much improved or Much improved) at Week 6
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TS-121 10mg | Clinical Global Impression-Improvement (CGI-I) | 33.3 percentage of participants |
| TS-121 50mg | Clinical Global Impression-Improvement (CGI-I) | 26.7 percentage of participants |
| Placebo | Clinical Global Impression-Improvement (CGI-I) | 18.8 percentage of participants |
Secondary
Clinical Global Impression-Severity (CGI-S)
The CGI-S is a clinician-rated scale to assess the severity of the disorder. The time frame for this scale is the past 7 days. The score ranges from 1 (Normal, not ill at all) to 7 (Among the most extremely ill patients).
Time frame: 6 weeks
Population: Participants who did not receive at least one dose of investigational product or did not have at least one post-dose assessments were not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TS-121 10mg | Clinical Global Impression-Severity (CGI-S) | -0.8 score on a scale |
| TS-121 50mg | Clinical Global Impression-Severity (CGI-S) | -0.7 score on a scale |
| Placebo | Clinical Global Impression-Severity (CGI-S) | -0.5 score on a scale |
Secondary
Hamilton Anxiety Scale (HAM-A)
The HAM-A is a clinician-rated scale to assess anxiety symptoms which consists from 14 items. The time frame for this scale is the past 7 days. Each item is scored on 5-point scale (0 \[absence of symptoms\] to 4 \[severe\]). The total score is the sum of 14 items and can take range from 0 to 56. A negative change from baseline indicates improvement.
Time frame: 6 weeks
Population: Participants who did not receive at least one dose of investigational product or did not have at least one post-dose assessments were not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TS-121 10mg | Hamilton Anxiety Scale (HAM-A) | -5.6 score on a scale |
| TS-121 50mg | Hamilton Anxiety Scale (HAM-A) | -3.4 score on a scale |
| Placebo | Hamilton Anxiety Scale (HAM-A) | -2.8 score on a scale |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS)
Percentage of MADRS responders (≥ 50% reduction in total score) at Week 6
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TS-121 10mg | Montgomery-Asberg Depression Rating Scale (MADRS) | 33.3 percentage of participants |
| TS-121 50mg | Montgomery-Asberg Depression Rating Scale (MADRS) | 20.0 percentage of participants |
| Placebo | Montgomery-Asberg Depression Rating Scale (MADRS) | 12.5 percentage of participants |
Secondary
Symptoms of Depression Questionnaire (SDQ)
The SDQ is a self-rated scale to assess the severity of symptoms across several subtypes of depression which consists from 44 items. The time frame for this scale is the past 7 days. Each item is scored on 6-point scale (1 \[better than normal\] to 6 \[severe\]). The total score is the sum of 44 items and can take range from 44 to 264. A negative change from baseline indicates improvement.
Time frame: 6 weeks
Population: Participants who did not receive at least one dose of investigational product or did not have at least one post-dose assessments were not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TS-121 10mg | Symptoms of Depression Questionnaire (SDQ) | -22.5 score on a scale |
| TS-121 50mg | Symptoms of Depression Questionnaire (SDQ) | -17.0 score on a scale |
| Placebo | Symptoms of Depression Questionnaire (SDQ) | -13.7 score on a scale |