Major Depressive Disorder MedDRA version: 8.1 Level: LLT Classification code 10025453 Term: Major depressive disorder NOS
Conditions
Interventions
Product Code: GW856553
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: GW856553
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5 -
Current Sponsor
Sponsors
GlaxoSmithKline
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A full list of Inclusion Criteria for MDD subjects can be found in the protocol. The criteria below are those that have been amended. 9. Subject currently meets the diagnosis for MDD (without psychotic features), recurrent, as defined in the DSM-IV-TR, diagnosed with a comprehensive psychiatric evaluation incorporating the MINI, as assessed* by a physician with adequate training in psychiatry. *Assessment by a physician with adequate training in psychiatry 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 and appropriate training in IDS-C scoring 10. 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. 11. 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 or inappropriately treated. 12. Subjects must exhibit moderate to severe levels of depression as defined by: • a minimum score of 17 on the QIDS-SR16 and a minimum score of 1 for the Items representing mood depression, interest, energy and psychomotor retardation when measured at the Screening visit (Week -1) and the Randomisation visit (Week 0). • a minimum total score of 36 on the IDS-C when measured at the Screening visit (Week -1) and at the Randomisation visit (Week 0) with a minimum score of 1 on Items representing mood depression, interest, energy, and psychomotor retardation. A full list of Inclusion Criteria for healthy subjects can be found in the protocol. The criterion below has been added. 2. Subject has total score =65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A full list of Exclusion Criteria for MDD subjects can be found in the protocol. The criteria below are those that have been amended. 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 significant cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions that, in the opinion of the investigator, place the subject at an unacceptable risk as a participant in this trial. 12. Subject has a positive urine test at the Screening or Randomisation (Week 0) visits for illicit drug use with the exception of barbiturates, whose sporadic use as hypnotics has been ascertained, the subject recommended for discontinuation pending verification for barbiturate dependence that will lead to exclusion from the study at any time; a history of DSM IV-TR diagnosis of substance abuse or dependence (other than nicotine) within the past 2 years. 13. Subject’s IDS-C assessment decreases by more than 25% between the Screening (Week -1) and Randomisation (Week 0) visits. 23. Women who have a positive serum Human Chorionic Gonadotropin (HCG) pregnancy test at the Screening visit (Week -1), a positive urine dipstick test at the Second Study Visit (Week 0), or who are lactating or planning to become pregnant within the next 12 weeks following the Screening visit. 25. The subject is currently receiving a chronic biological or pharmacologic anti-inflammatory therapy (includes both non-steroidal anti-inflammatory agents and corticosteroids); interferon therapy at any dose or did receive them within 6 months prior randomisation; vaccinations performed within 1 month or less prior to the Screening Visit. 26. Subjects who have taken other psychoactive drugs unles otherwise stated in the protocol between the Screening and the Randomisation visit (approximately 1-2 weeks). A full list of Exclusion Criteria for healthy subjects can be found in the protocol. The criteria below are those that have been amended. 13. Subject has a systolic blood pressure (SBP) > 160mmHg or a diastolic blood pressure (DBP) > 95mmHg at the Screening (Week –1) or Second Study Visit (Week 0) visit compatible with diagnosis of hypertension. 14. Women who have a positive serum Human Chorionic Gonadotropin (HCG) pregnancy test at the Screening visit (Week -1), a positive urine dipstick test at the Second Study Visit (Week 0), or who are lactating 15. Subjects have any screening electrocardiographic (ECG) parameter outside of the Sponsor-specified ranges; the ECG may be repeated once to see if the parameter returns to within range but any such abnormality must be resolved by the Second Study Visit. 16. The subject is currently receiving a chronic biological or pharmacologic anti-inflammatory therapy (includes both non-steroidal anti-inflammatory agents and corticosteroids); interferon therapy at any dose or did receive them within 6 months prior to the screening visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the antidepressant effects of GW856553X versus placebo treatment at Week 6 in adult subjects diagnosed with MDD with symptoms of loss of energy / interest and with psychomotor retardation. To measure the decrease of circulating plasma cytokines (either TNF-alpha or IL-6) produced by GW856553X versus placebo treatment in adult subjects diagnosed with MDD including symptoms of loss of energy / interest and with psychomotor retardation, as: - whole population sample, - sample of subjects with elevated cytokine levels at baseline or at screening - sample of subjects that respond to the treatment vs. non-responders at Week 6 according to the various clinical scores ;Secondary Objective: Safety and tolerability of GW856553X in patients with MDD. To evaluate the antidepressant effects of GW856553X versus placebo treatment at Weeks 1, 2, 3, 4 and 5 in adult subjects diagnosed with MDD including symptoms of loss of energy / interest and with psychomotor retardation. To evaluate the antidepressant effects of GW856553X versus placebo treatment in the sample of adult subjects diagnosed with MDD with symptoms of loss of energy / interest and with psychomotor retardation with abnormally elevated cytokine level at randomisation (Week 0). To evaluate the effects of GW856553X versus placebo treatment on specific clusters of symptoms possibly associate with pro-inflammatory cytokine effects (putative cytokine-related intermediate phenotypes) in the same adult subjects diagnosed with MDD, in particular: - Psychomotor retardation - Fatigue - Daytime sleepiness See the protocol for a complete listing of secondary objectives.;Primary end point(s): Changes from randomisation (Week 0) produced by GW856553X versus placebo at Week 6 in the following clinical scales: • Bech (6-item HAMD-17) score • IDS C total score • QIDS-SR16 total score Changes from randomisation (Week 0) associated with GW856553X versus placebo at week 6 in the morning plasma levels of | — |
Countries
Estonia
Outcome results
None listed