Venlafaxine ER Phase 3 Study for Major Depressive Disorder (MDD)

• Drug: venlafaxine ER 75 mg/day (fixed dose)
  Treatment phase: 8 weeks (37.5 mg/day for 1st week and 75 mg/day for 7 weeks), oral administration Tapering phase: 2 weeks (37.5 mg/day for the 1st week and placebo for the 2nd week), oral administration
• Drug: venlafaxine ER 75 mg/day to 225 mg/day (flexible dose)
  Treatment phase: 8 weeks (37.5 mg/day for the 1st week, 75 mg/day for the 2nd weeks, 75-150 mg for the 3rd week, 75-225 mg/day for the rest of 5 weeks), oral administration Tapering phase: 2 weeks (75/37.5 mg/day for the 1st week and 37.5 mg/day/placebo for the 2nd week), oral administration
• Drug: Placebo
  Treatment phase: 8 weeks (placebo), oral administration Tapering phase: 2 weeks (placebo), oral administration

• Experimental: venlafaxine ER 75 mg/day (fixed dose)
  Intervention: Drug: venlafaxine ER 75 mg/day (fixed dose)
• Experimental: venlafaxine ER 75 mg/day to 225 mg/day (flexible dose)
  Intervention: Drug: venlafaxine ER 75 mg/day to 225 mg/day (flexible dose)
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Kato M, Asami Y, Wajsbrot DB, Wang X, Boucher M, Prieto R, Pappadopulos E. Clustering patients by depression symptoms to predict venlafaxine ER antidepressant efficacy: Individual patient data analysis. J Psychiatr Res. 2020 Oct;129:160-167. doi: 10.1016/j.jpsychires.2020.06.011. Epub 2020 Jul 9.
• Higuchi T, Kamijima K, Nakagome K, Itamura R, Asami Y, Kuribayashi K, Imaeda T. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan. Int Clin Psychopharmacol. 2016 Jan;31(1):8-19. doi: 10.1097/YIC.0000000000000105.

Inclusion Criteria:

• Outpatient status.
• A primary diagnosis of MDD based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM- IV-TR), single or recurrent episode, without psychotic features.
• Depressive symptoms for at least 90 days in single episode and for at least 28 days in recurrent episode before the screening visit.
• A MADRS total score ?26 at the screening and baseline visits. And change of MADRS total score at baseline is not over 25% from the screening visit.
• A QIDS16-J-SR score ?16 at the screening and baseline visits.
• A score ?4 on the Clinical Global Impressions Scale-Severity (CGI-S) at the screening and baseline visits.

Exclusion Criteria:

• Subjects who concurrently have Axis II personality disorder or mental retardation according to DSM-IV diagnostic criteria.
• Subjects who meet DSM-IV criteria for current or past history of Schizophrenia, Paranoid Disorders, or any other Psychotic Disorders.
• Subjects who meet DSM-IV criteria for current or past history of Dementia.
• Subjects who meet DSM-IV criteria for current or past history of bipolar disorder, Posttraumatic Stress Disorder (PTSD) or Obsessive Compulsive Disorder (OCD).
• Subjects who meet DSM-IV criteria for current (within 12 months before the screening visit) generalized anxiety disorder, panic disorder, or social anxiety disorder considered by the investigator to be primary (causing a higher degree of distress or impairment than MDD).
• Subjects with a first degree relative with bipolar disorder.
• Subjects who are actively suicidal.
• History of non-responsive to 2 antidepressant treatment (at least 6-week usage for each) for the past or current episodes.
• History of Electroconvulsive therapy (ECT) at any time in the past.
• History of chronic treatment with benzodiazepines for longer than 6 months before the screening visit (Excluding subjects who have taken PRN benzodiazepine use, < 3 times/week).
• Any unstable hepatic, renal, pulmonary, cardiovascular (including uncontrolled hypertension), ophthalmologic, neurologic, or any other medical condition that in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of, the study.
• Known presence of raised intraocular pressure or history or presence of narrow angle glaucoma.
• Myocardial infarction within 180 days of the screening visit.
• Clinically important abnormalities, as determined by the investigator, on screening physical examination, electrocardiogram (ECG) or laboratory tests.
• Use of prohibited treatments