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

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

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).

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