A Study of the Effects of a New Antidepressant Treatment (GSK561679) in Females With Major Depressive Disorder
A Study of the Effects of a New Antidepressant Treatment (GSK561679) in Females With Major Depressive Disorder
This six-week study will evaluate the efficacy, safety and tolerability of GSK561679 compared
 to placebo in female subjects with major depressive disorder
This is a double-blind placebo controlled study to assess the CRF1 receptor antagonist,
 GSK561679, for treatment of depression in adult females diagnosed with Major Depressive
 Disorder (MDD). A treatment regimen of 350mg/day will be utilized to assess both efficacy and
 tolerability. Subjects will be randomized in equal numbers (n=75/arm) to the treatment arm
 and the placebo arm for a 6-week treatment period.

 Efficacy will be assessed by determining the change from baseline in symptoms of MDD and
 anxiety utilizing the Bech Melancholia scale (Bech), Hamilton Rating Scale for Depression
 (HamD17), Inventory of Depressive Symptomatology-Self-Report (IDS-SR), Clinical Global
 Impression - Severity of Illness (CGI-S), Clinical Global Impression - Global Improvement
 (CGI-I), Medical Outcomes Study 12-item Sleep Module (MOS 12), Cohen Perceived Stress Test
 (PSS), Hamilton Anxiety Scale (HamA), and Dexamethasone Suppression Test (DST). Safety and
 tolerability will be assessed by determining the incidence of adverse events (AEs), vital
 signs, BMI, weight, clinical laboratory parameters, including ECGs, during the treatment and
 pre & post-treatment phases, and Discontinuation Emergent Signs and Symptoms (DESS). In
 addition, the incidence of suicidality will be assessed by the Columbia Suicide Severity
 Rating Scale (C-SSRS).
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.