A Study of GW856553X For the Treatment of Depression

A Randomized, Double Blind, Placebo Controlled Study to Explore the Antidepressant Properties of P38a Kinase Inhibitor GW856553X 15mg Compared to PBO in Subjects With Major Depressive Disorder Exhibiting Symptoms of Loss of Energy and Interest and Psychomotor Retardation, for a Six Week Treatment Period

GW856553 is a novel compound, currently in development for the treatment of Major Depressive Disorder (MDD), and other indications. GW856553 inhibits a protein which is responsible for the production of some pro-inflammatory molecules, called cytokines. Increased blood levels of these molecules were seen in populations of MDD patients and this was more apparent in subjects with severe symptoms, psychomotor retardation and loss of energy. Aim of the present study is to assess whether GW856553, by inactivating this protein, is able to suppress the production of the cytokines, and ultimately relieving depression symptoms. In this study GW856553 or placebo is given to MDD patients 7.5md twice daily for 6 weeks.

A randomised, double-blind, placebo-controlled study to explore the antidepressant properties of the P38a kinase inhibitor GW856553X 15mg compared to placebo in subjects with Major Depressive Disorder exhibiting symptoms of loss of energy and interest, and psychomotor retardation, for a six week treatment period.

Inclusion Criteria:

• Male or female = 18 years of age and < 60 years,
• routine laboratory results within normal ranges,
• Body Mass Index within the range 18.5-35.0 kg/m2 inclusive.
• Subject must have had at least one previous major depressive episode with a diagnosis of MDD in his/her history, and had a successful pharmacological treatment of that episode, and is currently experiencing a recurrence of MDD presently un-medicated.
• Subjects must met the diagnosis of an episode of Major Depressive Disorder in the past 12 weeks but not greater than 24 months.

Exclusion Criteria:

• The subject has any history of liver disease.
• The subject has significant cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions that, in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as a participant in this trial.
• The subject has a history of autoimmune diseases.
• The subject has any active infectious diseases, including active tuberculosis or a history of active tuberculosis.
• The subject has a history of malignancy, except for surgically cured basal cell carcinoma or females with cured cervical carcinoma (> 2 yrs prior).
• The subject has a history of HIV or other immunosuppressive disease.
• The subject has uncontrolled diabetes.
• The subject is pregnant or nursing.
• 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).
• Subject has initiated psychotherapy within three months prior to the Screening visit, or plans to initiate psychotherapy during the trial.
• Subject has received electroconvulsive therapy or transcranial magnetic stimulation or vagal nerve stimulation within the six months prior to the Screening.
• The subject is currently receiving a chronic biological or pharmacologic anti-inflammatory therapy; interferon therapy at any dose or did receive them within 6 months prior randomisation.
• Subjects who have donated a unit of blood within the previous month or intends to donate in the month after completing the study