Major Depressive Disorder MedDRA version: 12.0 Level: LLT Classification code 10025453 Term: Major depressive disorder NOS
Conditions
Interventions
Product Name: GW856553
Product Code: GW856553
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: GW856553
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number:
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject is male or female = 18 years of age and = 60 years. To be eligible, female subjects must have a negative pregnancy test (i.e. serum beta hCG test) and be of: a. Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. b. Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up visit. 2. Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until the follow-up visit. 3. Body weight = 50 kg (110lbs) for males and = 45 kg (99lbs) for females. 4. Body mass index (BMI) within the range 18.5-35.0 kg/m2 inclusive. 5. The subject must have liver function (Alanine Aminotransferase [ALT], Aspartate Aminotransferase [AST] and total bilirubin) and Alkaline Phosphatase (ALP) tests within normal ranges at the Screening. 6. Subject must read and write at a level sufficient to understand and comply with the protocol requirements and complete study-related assessments. 7. Subjects must have the ability to comprehend the key components of the consent form and must provide signed and dated written informed consent prior to admission to the study. 8. Subject currently meets the diagnosis for MDD (without psychotic features), as defined in the DSM-IV-TR, diagnosed with a comprehensive psychiatric evaluation incorporating the MINI, as assessed* by a Board Certified psychiatrist. *Assessment 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 subjects with MDD. 9. 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. 10 Subject must have had at least one previous major depressive episode with a diagnosis of MDD in his/her history and is currently experiencing a recurrence of MDD. 11 Subjects must exhibit moderate to severe levels of depression as defined by: IDS-SR when measured at the Screening and Randomization visits: • a total score =38, and • a score =1 for each of the items representing mood (item 5; feeling sad), interest (item
Exclusion criteria
Exclusion criteria: 1. History of excessive regular alcohol consumption within 3 months of the study defined as: - For non-US sites: an average weekly intake of >21 units (or average daily intake >3 units) for males or >14 units (or average daily intake >2 units) for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits. - For US sites: an average weekly intake of >14 drinks (or average daily intake >2 drinks) for males or >7 drinks (or average daily intake >1 drink) for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits 2. The subject has any history of liver disease. 3. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening 4. The subject has a history of elevated liver function tests on more than one occasion (ALT, AST, and total bilirubin > 2 x ULN or ALP > 3 x ULN) in the past 7 months. 5. The subject has a significant cardiac, pulmonary, metabolic, renal, or gastrointestinal disease that, in the opinion of the investigator, places the subject at an unacceptable risk as a participant in this trial. 6. The subject has a history of autoimmune diseases. 7. The subject has any active infectious diseases, including active tuberculosis or a history of active tuberculosis. 8. The subject has a history of malignancy, except for surgically cured basal cell carcinoma or females with cured cervical carcinoma (> 2 yrs prior). 9. The subject has a history of HIV or other immunosuppressive disease. 10. The subject has uncontrolled diabetes. 11. The subject is pregnant or nursing. 12. Subject has a positive urine test at the Screening or Randomisation (Week 0) visits for illicit drug use with the exception of barbiturates see protocol for further information. 13. A history of DSM IV-TR diagnosis of substance abuse or dependence (other than nicotine) within the past 6 months. 14. Subject has: • Symptoms of the presenting illness which are better accounted for by another diagnosis*; or • A current DSM-IV-TR diagnosis of Panic Disorder; *view protocol for further information. 15. Subject has no contact with an adult on a daily basis (contact can be in person or via the telephone). 16. Subject has initiated psychotherapy within three months prior to the Screening visit, or plans to initiate psychotherapy during the trial. (View protocol for further information) 17. Subject has received electroconvulsive therapy or transcranial magnetic stimulation or vagal nerve stimulation within the six months prior to the Screening visit. 18. Subject, who, in the investigator’s judgment, poses a serious suicidal risk. View protocol for further information. 19. Subjects, who in the investigator's judgement, pose a significant homicidal risk or have ever been homicidal. 20. 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. 21. 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. 22. Subjects who are not euthyroid. View protocol for further information. 23. Women who have a positive serum (HCG) pregnancy test at the Screening visit, a positive urine pregnancy test at th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical antidepressant effects of GW856553 versus placebo treatment at Week 6 in adult subjects diagnosed with MDD with symptoms of decreased energy and interest, and with psychomotor retardation.;Secondary Objective: • Safety and tolerability of six weeks of dosing GW856553 in subjects with MDD. • To evaluate the antidepressant effects of GW856553 versus placebo treatment at Weeks 1, 2, 3, 4 and 5 in adult subjects diagnosed with MDD. • To measure the decrease of circulating plasma cytokines (TNFa and IL-6) associated with GW856553 versus placebo treatment in subjects with MDD as: • whole population sample • sample of subjects with elevated cytokine levels at baseline • sample of subjects that respond to the treatment vs. non responders at Week 6 according to the various clinical scores. For Exploratory Objectives view protocol pages 17-18 ;Primary end point(s): • Change from Randomization (Week 0) associated with GW856553 versus placebo at Week 6 in the Bech (6-item HAMD-17) score. | — |
Countries
Bulgaria, Estonia, Germany
Outcome results
None listed