A Ten-Week, Multicenter, Randomized, Double-Blind, Placebo and Active-Controlled, Parallel-Group, Flexible-Dose Study Evaluating the Efficacy, Safety, and Tolerability of GSK372475 (1.5 mg/day to 2.0 mg/day) or Extended Release Venlafaxine XR (150 mg/day to 225 mg/day) Compared to Placebo in Adult Subjects Diagnosed with Major Depressive Disorder.

Conditions: Major Depressive Disorder
MedDRA version: 8.1Level: LLTClassification code 10025453Term: Major depressive disorder NOS

Registration Number: EUCTR2005-003401-87-BE

Lead Sponsor: GlaxoSmithKline Research & Development

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 399

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1.Male or female outpatients aged 18-64 years, inclusive.
2.Subject currently meets the diagnosis for MDE associated with MDD, single episode or recurrent, according to DSM-IV-TR (296.2/296.3), diagnosed through a comprehensive psychiatric evaluation (in conjunction with the Mini International Neuropsychiatric Interview (MINI), Clinician Rated Version 5.0 [Sheehan, 1998]), as assessed by a physician with adequate training in psychiatry (e.g., Board Certification in psychiatry in US; Certificate of Completion of Specialist training in psychiatry in EU).
* Assessment by a physician with adequate training in psychiatry must include a face-to-face evaluation of the subject, but may be aided by subject evaluation conducted by a healthcare professional with a clinically relevant qualification (e.g., psychiatric nurse or psychologist) and a minimum of two years of documented experience assessing patients with MDD.
3.Subject must, in the investigator’s opinion based on clinical history, have met DSM-IV-TR (Appendix 6) criteria for their current MDE for at least 12 weeks but no greater than 24 months.
4.Subjects with an IVRS IDS-SR (Appendix 12) total score ?40 at the Screening and Randomization Visits.
5.Subjects must have a CGI-S (Appendix 11) score of ?4 at the Randomization Visit.
6.Subject must have the ability to comprehend the key components of the consent form and provide informed consent.
7.Subject must read and write at a level sufficient to complete study-related assessments.
8.A female subject is eligible to enter and participate in the study if she is of:
a.Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal)
•Post-menopausal females defined as being amenorrhoeic for greater than two years with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms). However, if indicated, this should be confirmed by estradiol and FSH levels consistent with menopause (according to local laboratory ranges).
Women who have not been confirmed as post-menopausal should be advised to use contraception as outlined below.
•Pre-menopausal females with a documented (medical report verification) hysterectomy and/or bilateral oophorectomy only when reproductive status has been confirmed by hormone level assessment.
b.Child-bearing potential, has a negative pregnancy test at Screening and randomization, and agrees to satisfy one of the following requirements:
•Complete abstinence from intercourse from commencement of last normal menstrual period (2 weeks minimum) prior to administration of the first dose of study drug, throughout the Treatment Phase, and for a minimum of 8 weeks after completion or premature discontinuation from the study drug; or,
•Established use of acceptable methods of contraception from commencement of last normal menstrual period (3 weeks minimum) prior to administration of the first dose of study medication, throughout the Treatment Phase, and for a minimum of 8 weeks after completion or premature discontinuation from the study drug. Acceptable methods of birth control are listed below:
•Female sterilization (documented bilateral tubal ligation); or
•Sterilization (vasectomy) of male partner prior to commencement of female subject’s last normal menstrual period prior to administration of the first dose of study

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1.Subject’s IVRS IDS-SR (Appendix 12) assessment increases or decreases by more than 25% between the Screening (Week -1) and Randomization (Week 0) visits .
2.Subject has:
a.Symptoms of the presenting illness which are better accounted for by another diagnosis*; or
b.A current DSM-IV-TR diagnosis of Panic Disorder; or
c.Symptoms of generalized anxiety or panic attacks that in the investigator’s judgement could interfere with their ability to complete the trial; or
d.A current DSM-IV-TR diagnosis of Antisocial or Borderline Personality Disorder, Dementia, or another current DSM-IV-TR Axis II diagnosis that would suggest nonresponsiveness to pharmacotherapy or non-compliance with the protocol; or
e.A current (or within six months prior to the Screening visit) diagnosis of anorexia nervosa or bulimia; or
f.A DSM-IV-TR diagnosis of Bipolar Disorder, Schizophrenia, or other psychotic disorder(s).
*Major depressive disorder should be the condition that precipitates the evaluation (principal diagnosis) and the condition that best accounts for the clinical presentation (primary diagnosis). Secondary diagnoses of other anxiety disorders such as generalized anxiety disorder, posttraumatic stress disorder, social anxiety disorder, acute stress disorder, and obsessive-compulsive disorder are permissible.
3.Subject has an unstable medical disorder; or a disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of GSK372475 or venlafaxine XR or may pose a safety concern, or interfere with the accurate assessment of safety or efficacy.
4.Subject has no contact with an adult on a daily basis (i.e., subjects who are not living with at least one other adult or subjects who do not have an adult who contacts them on a daily basis). This criterion only applies to sites in Canada, Mexico, Central and South America.
5.Patients under specific law protection in France named curatelle or tutelle (Guardianship) This criterion applies only to sites in France.
6.Subject has initiated psychotherapy within three months prior to the Screening (Week –1) visit, or plans to initiate psychotherapy during the trial. Subjects who present with their current MDD diagnosis despite longer-term psychotherapy (i.e. greater than three months prior to the Screening visit) may be included.
7.Subject has received electroconvulsive therapy or transcranial magnetic stimulation within the six months prior to the Screening (Week –1) visit.
8.Subject has previously failed an adequate therapeutic course of pharmacotherapy for MDD (e.g., for >4 weeks) from two different classes of antidepressants or two antidepressants within the same class.
9.Subject has a positive urine test at the Screening (Week –1) or Randomization (Week 0) visits for illicit drug use; a history of DSM diagnosed alcohol or substance abuse or dependence (other than nicotine) within the past 2 years or a blood alcohol level of >15mg/dl (0.015 %) at the Screening visit (Week –1). Note – subjects must be told to avoid consumption of alcoholic beverages for at least eight hours prior to their Screening visit. The use of alcohol by subjects participating in the study is not recommended.
10.Subject, who, in the investigator’s judgement, poses a homicidal or serious suicidal risk, has had any previous suicide attempt, a family history of suicide attempts, or who has ever been hom