Clinical Study to Test a New Drug to Treat Major Depression
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: GW856553; Placebo
Intervention description: Wet Granulated, film coated white, 9mm round, biconvex, plain faced tablets, containing 7.5 mg of GW856553; Film coated white, 9mm round, biconvex, plain faced tablets obtained by direct compression.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 128.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Lack of interest and energy; Psychomotor retardation; Cytokines; Major Depressive disorder

Summary:

      In this randomized, double-blind, multi-centre, placebo controlled, exploratory, adaptive
      design study, the antidepressant and plasma cytokine lowering effects of the GW856553 will be
      investigated in adult subjects diagnosed with MDD. Subjects will receive oral doses of
      GW856553 or placebo for six weeks. Safety, tolerability, pharmacokinetics and
      pharmacodynamics, defined as biomarkers in blood and clinical symptoms, will be assessed.

      The primary endpoint is the change from baseline associated with GW856553 versus placebo at
      Week 6 in the Bech (6-item HAMD-17) score. Interim analyses of the primary endpoint will be
      performed throughout the study to potentially adapt the study design by changing the
      randomization ratio and/ or reducing the total number of subjects to be randomized into the
      study. Exploratory analyses will be performed by associating changes in cytokine levels and
      selected clinical symptoms; PK/PD modelling will also be used to identify the most sensitive
      clinical and biological markers.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Adult subjects with primary diagnosis of moderate to severe MDD without psychotic
             features, for at least 4 weeks and one previous MDD episode

          -  Males or Females who agree to use protocol specified contraception if of child bearing
             potential

          -  BMI 18.5-35.0 kg/m2

          -  Normal liver function tests

        Key Exclusion Criteria:

          -  History of liver disease or positive hepatitis B surface antigen or hepatitis C
             antibody in the last 3 months

          -  Elevated liver function tests on >2 ocassions in the last 7 months

          -  Significant medical illness, autoimmune disease or infectious disease

          -  Pregnant or nursing females

          -  Excessive and regular alcohol consumption

          -  History of substance abuse or dependence in past 6 months or positive urine drug
             screen

          -  Significant suicidal or homicidal risk

          -  Currently receiving chronic biological or pharmacologic anti-inflammatory therapy or
             is not euthyroid

          -  Psychoactive drugs within 1 week or 5 half lives of randomization visit

          -  Treatment resistant subjects