A Study of the Effects of a New Antidepressant Treatment (GSK561679) in Females With Major Depressive Disorder
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: GSK561679; Placebo
Intervention description: GSK561679; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 150.0
Sex: Female
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Depressive Disorder, Major

Summary:

      This six-week study will evaluate the efficacy, safety and tolerability of GSK561679 compared
      to placebo in female subjects with major depressive disorder
    

Eligibility criteria:

        Inclusion criteria:

          -  Female outpatients aged 25-64 years, inclusive.

          -  Subjects must have the ability to comprehend the consent form, and provide informed
             consent.

          -  Subject currently meets the diagnosis for MDD (without psychotic features), single
             episode or recurrent, as defined in the DSM-IV-TR, diagnosed with SCID-CT (Structural
             Clinical Interview for DSM-IV Axis I disorders - Clinical Trials Version) as assessed
             * by a physician with adequate training in psychiatry (e.g., Board Certification in
             psychiatry in the US or equivalent local qualification in other countries)

          -  Subject must, in the investigator's opinion based on clinical history, have met DSM
             IV-TR criteria for their current major depressive episode for at least 4 weeks but for
             no greater than 24 months.

          -  Subject has an IVRS HamD17 total score ≥ 23 at the Screening and Randomization Visits
             and the HAMD17 score is confirmed to be at least 20 by the Independent Efficacy Rater
             at the Screening and Randomization Visits.

          -  The subject is eligible to enter and participate in this study if she is not lactating
             and:

          -  Is of non-childbearing potential (i.e., physiologically incapable of becoming
             pregnant, including any female who is post-menopausal [defined as one year without
             menses]); is surgically sterile [via hysterectomy and/or removal of the ovaries] or,
             is of child-bearing potential, has a negative pregnancy test at both screening and
             baseline (prior to investigational product administration), and agrees to acceptable
             methods of contraception.

        Exclusion Criteria

          -  Symptoms of the presenting illness which are better accounted for by another
             diagnosis*; or

          -  A current DSM-IV-TR Axis I diagnosis of Dementia; or

          -  Antisocial or Borderline Personality Disorder or other current DSM-IV-TR Axis II
             diagnosis that would suggest unresponsiveness to pharmacotherapy or non-compliance
             with the protocol; or

          -  A current (or within 12 months prior to the Screening visit) diagnosis of anorexia
             nervosa or bulimia; or

          -  A lifetime history of Schizophrenia, Schizoaffective Disorder, or a Bipolar Disorder.

          -  Subject has an unstable medical disorder or a disorder that would interfere with the
             action, absorption, distribution, metabolism, or excretion of GSK561679 or may pose a
             safety concern, or interfere with the accurate assessment of safety or efficacy.

          -  Subject has initiated psychotherapy within one month prior to the Screening 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) and who agree to maintain the same therapy
             schedule during the trial may be included.

          -  Subject has received vagus nerve stimulation, electroconvulsive therapy, or
             transcranial magnetic stimulation within the six months prior to the Screening visit.

          -  Subject has previously failed adequate therapeutic courses of pharmacotherapy for MDD
             (e.g., maximum-labeled/tolerated doses for ≥ 4 weeks) from two different classes of
             antidepressants.

          -  Subject, who, in the investigator's judgement, poses a homicidal or serious suicidal
             risk, has had any previous suicide attempt (including aborted, interrupted or
             ineffective attempts) or who has ever been homicidal.

          -  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 Canadian sites and
             others where this is a local requirementa.

          -  Subject has a positive urine test at screening for illegal drug use and/or history of
             substance abuse or dependence (alcohol or drugs as defined by DSM-IV TR criteria)
             within the past 12 months. Subject has a blood alcohol level of ≥ 15mg/dL (0.015%) at
             the Screening Visit. If a subject has a positive blood alcohol or positive illegal
             drug results, the subject is provisionally excluded and the test cannot be repeated
             without prior approval of the GSK medical monitor. NOTE: Subjects must be told to
             avoid consumption of alcoholic beverages for at least eight hours prior to the
             Screening Visit. The use of alcohol by subjects participating in the study is not
             recommended.

          -  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.

          -  Subject has a systolic blood pressure (SBP) > 160mmHg or a diastolic blood pressure
             (DBP) ≥ 100 mmHg verified by repeated measurement at the Screening or Randomization
             visit.

          -  Subject is (a) currently participating in another clinical study in which the subject
             is or will be exposed to an investigational or non-investigational drug or device; or
             (b) has participated in a clinical study for an illness unrelated to
             depression/anxiety within the preceding month; or (c) has participated in a clinical
             study related to depression/anxiety within the preceding six months.

          -  Documented history of hepato-biliary disease including a history of, or positive
             laboratory results for hepatitis (hepatitis B surface antigen and/or hepatitis C
             antibody) at Screening, and/or clinically significant hepatic enzyme elevation
             13.Subjects who are not euthyroid as evidenced by normal TSH (subjects maintained on
             thyroid medication must be euthyroid for a period of at least six months prior to the
             screen visit).

          -  Subject has a positive serum Human Chorionic Gonadotropin (HCG) pregnancy test at
             screen visit, a positive urine dipstick test at randomization, or who is lactating or
             planning to become pregnant within the next 13 weeks following the Screen Visit.

          -  Subject has clinical evidence of, or ECG results indicating any of the following at
             either screen or Randomization Visit unless repeat ECG shows that the parameter had
             returned to within normal range by the Randomisation Visit. (The ECG may be repeated
             to see if the parameter returns to within range):

               -  QTc > 450 msec;

               -  any cardiac condition or ECG evidence that the investigator feels may predispose
                  the subject to ischemia or arrhythmia; or

               -  any ECG abnormality that, in the investigator's judgment, may pose a potential
                  safety concern.

          -  Subject has taken other psychoactive drugs within one week prior to the
             ScreeningScreening Randomization Visit

          -  Subject has taken systemic corticosteroids acutely within two weeks or chronically
             within the last 6 months of the Randomization Visit (NOTE: Topical hydrocortisone and
             inhaled corticosteroids are allowed).

          -  Subject has taken other (non-psychoactive) prescription, non-prescription, dietary, or
             herbal products metabolized via the cytochrome P450 3A4 pathway, or P-gp substrates
             with a narrow therapeutic index within 2 weeks (or 5 half-lives, whichever is longer)
             prior to the Randomization Visit.

          -  Subject has taken other (non-psychoactive) prescription, non-prescription, dietary, or
             herbal products that are potent inducers or inhibitors of the cytochrome P450 3A4
             pathway for 2 weeks (or 5 half lives, whichever is longer) prior to the Randomization
             Visit.

          -  Subject has previously participated in an investigational trial involving GSK561679 or
             closely related compounds.

          -  Subject has a history of allergic reaction to, or significant adverse effects from
             excipients in the GSK561679 tablet.