A Ten-Week, Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group, Flexible-Dose Study Evaluating the Efficacy, Safety, and Tolerability of GSK372475 or Paroxetine Compared to Placebo in Adult Subjects Diagnosed with Major Depressive Disorder - ND

Conditions: major depressive disorder
MedDRA version: 9.1Level: LLTClassification code 10057840Term: Major depression

Registration Number: EUCTR2005-003400-11-IT

Lead Sponsor: GlaxoSmithKline Research Development Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 492

Inclusion Criteria

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 criteria for their current MDE for at least 12 weeks but no greater than 24 months. 4. Subjects with an IVRS IDS-SR total score 61619;25 at the Screening and Randomization Visits. 5. In addition, subjects should exhibit symptoms of decreased energy, pleasure, and interest as measured by a score of at least one on four of the five items item 19 General interest/involvement , item 20 Energy/fatiguability , item 21 Pleasure/Enjoyment , item 22 Sexual interest , item 30 Leaden paralysis/physical energy , and a total of at least 7 on the 5-item sub-scale of the IDS-SR at Screening and Randomization. 6. Subjects must have a CGI-S score of 61619;4 at the Randomization Visit. 7. Subject must have the ability to comprehend the key components of the consent form and provide informed consent. 8. Subject must read and write at a level sufficient to complete study-related assessments. 9. 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

Exclusion Criteria

1. Subject s IVRS IDS-SR assessment increases or decreases by more than 25 between the Screening Week -1 and Randomization Week 0 visits or subject s IDS 5-item subscale score falls to 7 items 19, 20, 21, 22, 30 . 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 .3. Subject has an unstable medical disorder; or a disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of GSK372475 or may pose a safety concern, or interfere with the accurate assessment of safety or efficacy.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 61619;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 61619;15mg/dl 0.015 at the Screening visit Week 1 . 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 homicidal. 11. Subject has any laboratory abnormality that in the investigator s judgement is considered to be clinically significant and could potentially affect subject safety or study outcome. 12. Female subject is pregnant, lactating, or does not agree to use contraceptive method s specified in the protocol to avoid pregnancy during the study. 13. Subject has a current or past history of seizure except for febrile seizures in childhood , or has a condition which, in the opinion of the investigator, predisposes the subject to seizures. 14. Subject has a systolic blood pressure SBP 140mmHg or a diastolic blood pressure DBP 61619;90mmHg at the Screening Week 1 or Randomization Week 0 visit. 15. Subject has chronic hepatitis B and C, as evidenced by positive Hepatitis B surface antigen HBsAg or Hepatitis C antibody. 16. Subject has taken g. any psychotropic drug within four weeks prior to the Randomization Week 0 visit, h. any psychoactive herbal treatment 17. Subjects who have taken other drugs known to inhibit P-glycop