The purpose of this study is to determine if CX157 is effective and safe in patients with treatment of treatment resistant depression over six weeks of treatment.

The primary objective of this study is to examine the efficacy of CX157 Modified Release Tablet, 125 mg administered twice per day (BID) as compared to placebo in subjects with Treatment Resistant Depression (TRD). Secondary objectives are to evaluate the safety and tolerability of CX157 Modified Release Tablet, 125 mg BID in TRD subjects and characterize steady-state pharmacokinetic profile and explore pharmacodynamic relationships.

Inclusion Criteria:

1. Male or female, 20 to 65 years of age
2. Able to read, understand and converse in English and provide written, dated informed consent
3. Diagnosed with Major Depressive Disorder (MDD)and Treatment Resistant Depression(TRD)
4. Females on acceptable method of contraception

Exclusion Criteria:

1. Major depressive episode greater than five years
2. A history of a Substance Use Disorder with the exception of nicotine dependence in the past 12 months
3. Obsessive-Compulsive Disorder (OCD), Panic Disorder, Post-traumatic Stress Disorder (PTSD
4. A history of schizophrenia or schizoaffective disorders
5. A history of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified, within the past five years
6. A history of Antisocial Personality Disorder or Borderline Personality Disorder
7. Recent suicidal behavior and is at risk of such behavior during the course of the study
8. Electroconvulsive therapy (ECT) within the past five years
9. Transcranial Magnetic Stimulation (TMS) for the treatment of the current episode of depression
10. Vagus Nerve Stimulation (VNS) at any time
11. Any psychoactive drugs within one to four weeks prior to the randomization visit depending on the type of drug
12. Significant abnormality on the screening physical examination
13. Significant cardiac abnormalities such as uncontrolled hypertension, recent myocardial infarction, Congestive heart failure (CHF), Angina pectoris
14. A history within the past two years of significant head trauma, surgical procedure involving the brain,degenerative central nervous system disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation
15. A history of hypothyroidism and has been on a stable dosage of thyroid replacement medication for less than six months
16. A history of hyperthyroidism which was treated (medically or surgically) less than six months prior to screening
17. Participation in an investigational study in the past one month
18. A positive screening urine test for drugs of abuse
19. Female subject who is pregnant or lactating