Inclusion Criteria:  Male or female, aged 18 to 70 years at Screening. Diagnosis of Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) for either recurrent or single episode MDD without psychotic features that is confirmed by the Mini International Neuropsychiatric Interview (MINI). Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≥26 for the current MDE at all Screening visits and Baseline (Day 1). CGI-S score of ≥4 (moderately ill or worse) at all Screening visits and Baseline. History of inadequate response to ≥2 but ≤4 prior ADT therapies (including the current ADT for the current MDE) ≥ 2 weeks at Screening and ≥ 8 weeks at Baseline. Stable therapeutic dose of one of the following ADTs for the current MDE for ≥2 weeks prior to Screening and maintain the therapeutic dose throughout the study: citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine (IR or XR), desvenlafaxine, or vortioxetine. Detectable blood level of the approved ADT at Visits 1 and 2 of the Screening Period.  Exclusion Criteria:  MADRS Total Score improvement of ≥25% from the highest to the lowest score at any visit during the Screening Period. Clinically significant abnormal laboratory profiles, vital signs, or electrocardiograms (ECGs), per Investigator judgment. Judged by the Investigator to be at significant risk for suicide, violence, or homicide; or answers 'Yes' to items 4 or 5 on the Suicidal Ideation section of the C-SSRS at Screening or at Baseline; or has attempted suicide within the 6 months prior to Screening. History of psychotic disorder, including but not limited to schizophrenia, MDD with psychotic features, or bipolar I/II disorder with psychotic features. History of PTSD, OCD, panic disorder, intellectual disability, autism, acute stress disorder, or Cluster A or B personality disorder (per DSM-5 criteria). Any condition or procedure that may interfere with the absorption, metabolism, or elimination of the study medication (e.g., cholecystectomy or gastric bypass). In the Investigator's opinion, is unlikely to comply with the protocol or is unsuitable for any other reason. History of alcohol and/or substance use disorder within 6 months prior to Screening or is currently using or has positive results at Screening for drugs of abuse or has a positive alcohol result at any Screening or Baseline visit.