To compare the antidepressant efficacy and safety of subjects receiving DVS-233 SR versus subjects receiving placebo.

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

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

Criteria

Inclusion Criteria:

• Outpatients.
• Men and women 18 to 75 years of age, 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 barrier contraception.
• 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 prior to the screening visit.
• Minimum screening and study day –1 (baseline) scores of 20 on the Hamilton Psychiatric Rating Scale for Depression (HAM-D17).
• 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 extended release [ER]) within 90 days of study day 1.
• Known hypersensitivity to venlafaxine (IR or ER).
• Significant risk of suicide based on clinical judgment. 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 neurological 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. Refer to Excluded Treatments chart and Sections 16.1 and 16.2 (Permitted Treatment and Prohibited Treatment) for treatments and associated timeframes.

California
      Pharmacology Research Institute, Newport Beach,  California,  92660-2452,  United States
      Pacific Clinical Research, Orange,  California,  92868,  United States
Colorado
      Feiger Health Research Center, Wheat Ridge,  Colorado,  80033,  United States
Connecticut
      New Britain General Hospital, New Britain,  Connecticut,  06050,  United States
District of Columbia
      The George Washington University Medical Center, Washington,  District of Columbia,  20037,  United States
Florida
      Coordinated Research of Florida, Inc., Winter Park,  Florida,  32789,  United States
      Comprehensive NeuroScience, Inc., St. Petersburg,  Florida,  33702,  United States
Illinois
      Chicago Center for Clinical Research, Chicago,  Illinois,  60610-4324,  United States
Michigan
      Summit Research Network, Inc., Okemos,  Michigan,  48864,  United States
Nebraska
      Creighton University, Department of Psychiatry, Omaha,  Nebraska,  68131,  United States
New Jersey
      Center for Emotional Fitness, Moorestown,  New Jersey,  08057,  United States
New York
      The Medical Research Network, L.L.C., New York,  New York,  10024,  United States
Pennsylvania
      Southeastern Pennsylvania Medical Institute, Havertown,  Pennsylvania,  19083,  United States
Texas
      Future Search Trials, Austin,  Texas,  78756,  United States
      University of Texas Southwestern Medical Center at Dallas, Dallas,  Texas,  75390-9101,  United States

Study ID Numbers:  3151A1-304-US
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  June 23, 2003
ClinicalTrials.gov Identifier:  NCT00063206
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08