A Study to Evaluate the Safety and Efficacy of TS-121 as an Adjunctive Treatment for Major Depressive Disorder

Study Overview
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Brief Summary
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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).

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of TS-121 as an Adjunctive Treatment for Patients With Major Depressive Disorder With an Inadequate Response to Current Antidepressant Treatment

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: TS-121 10 mg
* Drug: TS-121 50 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males and females between 18 and 65 years of age inclusive (at time of initial informed consent) Patients with a current diagnosis of MDD by DSM-5, confirmed through a structured interview using MINI 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 Patients who willing to remain on the same primary SSRI, SNRI or bupropion and fixed dose throughout the course of the study Patients who meet the total score on the HAM-D as listed below HAM-D ≥ 18 at Screening HAM-D ≥ 18 at Baseline Body Mass Index (BMI) ≥ 18 and ≤ 38 kg/m2 Exclusion Criteria: Patients with inadequate response to ≥2 prior antidepressant treatments (not including current antidepressant) of at least 4 weeks duration each for the current episode Patients whose current depressive episode is diagnosed with psychotic features, catatonic features, post-partum (primary onset), or is secondary to a general medical disorder Patients with a diagnosis of any of the following DSM-5 class disorders Schizophrenia spectrum and other psychotic disorders Bipolar and related disorders 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] Obsessive-compulsive and related disorders Trauma- and Stressor-related disorders 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 Patients who received repetitive transcranial magnetic stimulation (rTMS) within 12 months of Screening or plan to receive rTMS during the study Patients who plan to initiate or terminate cognitive or behavioral psychotherapy or alter the frequency of ongoing therapy during this study Patients who have attempted suicide within the past 6 months Patients with history or presence of intellectual disability, pervasive developmental disorder, cognitive disorder, neurodegenerative disorder, or brain injury Patients with any history or complication of convulsive disorder Patients who are undergoing treatment with psychotropic medications, benzodiazepines, metyrapone, lithium and/or corticosteroids Patients who are taking moderate to strong CYP3A4 inhibitors/inducers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TS-121 10mg<br> | Drug: TS-121 10 mg<br>* Orally taken once daily<br>|
| Experimental: TS-121 50mg<br> | Drug: TS-121 50 mg<br>* Orally taken once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Orally taken once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 weeks | 
| 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. | 6 weeks | 
| 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). | 6 weeks | 
| Montgomery-Asberg Depression Rating Scale (MADRS) | Percentage of MADRS responders (≥ 50% reduction in total score) at Week 6 | 6 weeks | 
| Clinical Global Impression-Improvement (CGI-I) | Percentage of CGI-I improvers (Very much improved or Much improved) at Week 6 | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, Adjunctive Treatment