The main objective of this study is to compare the antidepressant efficacy and safety of DVS-233 SR versus placebo in adult outpatients with major depressive disorder (MDD). After a screening period of 10 + or - 4 days, eligible subjects will be treated for 8 weeks. An additional 2 weeks will be allowed for tapering test article. Subjects will return for a follow-up visit 7 days after discontinuing test article.

Condition	Treatment or Intervention	Phase
Major Depressive Disorder	Drug: DVS-233 SR  Drug: Venlafaxine ER	Phase III

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Outpatients.
• Men and women aged 18 to 75 years, inclusive. Sexually active women participating in the study must use a medically acceptable form of contraception. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices, or properly used double-barrier contraception, eg, condom plus diaphragm.
• Subjects must have a primary diagnosis of major depressive disorder (MDD) based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), single or recurrent episode, without psychotic features. If other allowable psychiatric diagnoses are present, MDD must be the predominant psychiatric disorder present. (See Exclusion Criterion 6 for other psychiatric diagnoses that are not allowable.)
• Depressive symptoms for at least 30 days before the screening visit.
• Minimum screening and study day –1 (baseline) scores of 22 on the Hamilton Psychiatric Rating Scale for Depression (HAMD17).
• Minimum screening and study day –1 (baseline) scores of 2 on item 1 (depressed mood) of the Hamilton Psychiatric Rating Scale for Depression (HAM-D17).
• Minimum screening and study day –1 (baseline) scores of 4 on Clinical Global Impressions-Severity scale (CGI-S).
• Signed and dated informed consent before any screening procedures.

Exclusion Criteria:

• Treatment with DVS-233 SR at any time in the past.
• Treatment with venlafaxine (immediate release [IR] or ER) within 90 days of study day 1.
• Known hypersensitivity to venlafaxine (IR or ER).
• Significant risk of suicide based on clinical judgment, including common suicidal thoughts, and suicide being considered as a possible solution, even without specific plans or intention.
• Women who are pregnant, breastfeeding, or planning to become pregnant during the study.
• Current (within 12 months of baseline) psychoactive substance abuse or dependence (including alcohol), manic episode, posttraumatic stress disorder, obsessive-compulsive disorder, or a lifetime diagnosis of bipolar or psychotic disorder as assessed by the modified Mini International Neuropsychiatric Interview (MINI). Current (within 12 months of baseline) generalized anxiety disorder, panic disorder, or social anxiety disorder as assessed by the modified MINI and considered by the investigator to be primary, causing a higher degree of distress or impairment than MDD. Presence (within 12 months of baseline) of a clinically important personality disorder (such as antisocial, schizotypal, histrionic, borderline, narcissistic).
• A Covi Anxiety Scale total score greater than the Raskin Depression Scale total score at screening or at study day –1 (baseline). A Covi Anxiety score greater than 3 on any single item or a total score greater than 9 at screening or at study day –1 (baseline).
• Depression associated with the presence of an organic mental disorder due to a general medical condition or a neurologic disorder.
• History of a seizure disorder other than a single childhood febrile seizure.
• History or presence of clinically important hepatic or renal disease or other medical disease that might confound the study or be detrimental to the subject (eg, clinically important cardiac arrhythmia, uncontrolled diabetes, uncontrolled hypertension).
• History or current evidence of gastrointestinal disease known to interfere with the absorption or excretion of drugs or history of surgery known to interfere with the absorption or excretion of drugs.
• History of neoplastic disorder (within 2 years), with the exception of basal or squamous cell carcinoma of the skin.
• Known presence of raised intraocular pressure or history of narrow-angle glaucoma.
• Major acute illness during the 90 days before screening.
• Myocardial infarction within 180 days before screening.
• Clinically important abnormalities on screening physical examination, electrocardiogram (ECG), or laboratory tests. Clinically important abnormalities on screening urine drug screen (UDS). The investigator and medical monitor will evaluate a positive UDS as to the potential impact and continued participation of the subject in the study.
• Use of prohibited treatments.

Arizona
      Pivotal Research Centers, Peoria,  Arizona,  85381-4828,  United States; Recruiting
California
      UCSD Outpatient, Gifford Clinic, San Diego,  California,  92103,  United States; Recruiting
District of Columbia
      George Washington University Medical Center, Washington,  District of Columbia,  20037,  United States; Recruiting
Florida
      CORE Research, Inc., Leesburg,  Florida,  34748,  United States; Recruiting
      Kolin Research Group, Winter Park,  Florida,  32789,  United States; Recruiting
Georgia
      Atlanta Center for Medical Research, Atlanta,  Georgia,  30308,  United States; Recruiting
Kentucky
      Hartford Research Group, Florence,  Kentucky,  41042,  United States; Recruiting
Maryland
      Capital Clinical Research Associates, Rockville,  Maryland,  20852,  United States; Recruiting
Ohio
      Midwest Clinical Research Center, Dayton,  Ohio,  45408,  United States; Recruiting
South Carolina
      Southeast Health Consultants, LLC, Charleston,  South Carolina,  29407,  United States; Recruiting
Texas
      Research Testing, Inc., Houston,  Texas,  77004,  United States; Recruiting
Washington
      Center for Anxiety and Depression, Seattle,  Washington,  98105,  United States; Recruiting
      Summit Research Network (Seattle) LLC, Seattle,  Washington,  98104,  United States; Recruiting
      Northwest Clinical Research Center, Bellevue,  Washington,  98004,  United States; Recruiting
Wisconsin
      Northbrooke Research Center, Brown Deer,  Wisconsin,  53223,  United States; Recruiting

Study ID Numbers:  3151A1-317-US
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  July 13, 2004
ClinicalTrials.gov Identifier:  NCT00087737
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08