Primary Objective: To compare the efficacy and safety of DVS-233 SR versus placebo treatment in reducing the relapse rate of depressive symptoms in subjects with major depressive disorder (MDD), and to compare the percentages of relapse in terms of time to relapse between DVS-233 SR and placebo treatment groups by using survival analysis.

Secondary Objective: To assess the response of subjects on DVS-233 SR versus placebo for the clinical global evaluation, functionality, general well-being, pain, and absence of symptoms (Hamilton Psychiatric Rating Scale for Depression, 17-item [HAM-D17] < 7).

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 in the open-label phase:

• 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 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 psychiatric diagnoses that are not allowable.)
• Depressive symptoms for at least 30 days before entry in the study.
• Minimum screening and baseline (study day –1) total scores of 20 on the Hamilton Psychiatric Rating Scale for depression, 17 items (HAM-D17).
• Minimum screening and baseline (study day –1) total scores of 2 on item 1 (depressed mood) of the Hamilton Psychiatric Rating Scale for Depression (HAM-D17).
• Minimum screening and baseline (study day –1) scores of 4 on the Clinical Global Impressions-Severity scale (CGI-S).
• Signed and dated informed consent before any screening procedures.

Inclusion criterion in the double-blind phase of the study:

• Should have responded to the open-label treatment with DVS-233 SR as shown by having a HAM-D17 total score equal to or less than 11 on study day 84.

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. 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 Scale 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 (e.g., 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), laboratory tests. Clinically important abnormalities on 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 17.1 and 17.2 (Permitted Treatment and Prohibited Treatment) for treatments and associated timeframes.

California
      Pharmacology Research Institute, Northridge,  California,  91324,  United States; Recruiting
      Irvine Center for Clinical Research, Irvine,  California,  92618,  United States; Recruiting
      Southwestern Research, Inc., Beverly Hills,  California,  90210,  United States; Recruiting
Colorado
      Research Site, Denver,  Colorado,  80212,  United States; Recruiting
Florida
      Comprehensive NeuroScience, Inc., Sarasota,  Florida,  34232,  United States; Recruiting
Georgia
      Carman Research, Smyrna,  Georgia,  30080,  United States; Recruiting
Illinois
      Cunningham Clinical Research Associate, Edwardsville,  Illinois,  62025,  United States; Recruiting
Kansas
      Psychiatric Research Institute, Wichita,  Kansas,  67214,  United States; Recruiting
Louisiana
      Louisianna State University Medical Center, Shreveport,  Louisiana,  71130-3932,  United States; Recruiting
Michigan
      Summit Research Network (Michigan), Inc., Okemos,  Michigan,  48864,  United States; Recruiting
Minnesota
      Psychopharmacology Research, St. Paul,  Minnesota,  55101,  United States; Recruiting
Ohio
      NorthCoast Clinical Trials, Inc., Beechwood,  Ohio,  44124,  United States; Recruiting
Pennsylvania
      University  of  Pennsylvania  Medical  Center, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
Texas
      San Antonio Center for Clinical Research, San Antonio,  Texas,  78229,  United States; Recruiting
Wisconsin
      Dean Foundation, Middleton,  Wisconsin,  53562,  United States; Recruiting

Study ID Numbers:  3151A1-302-WW
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  January 7, 2004
ClinicalTrials.gov Identifier:  NCT00075257
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08