| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Define profile of neurobiological and psychological response to GW679769 (80-120 mg/day) compared to placebo |
|
| E.2.2 | Secondary objectives of the trial |
Define profile of neurobiological and psychological response to paroxetine compared to placebo.
Quantify differential sensitivity of fMRI (and other biomarkers) to detect antidepressant treatment effects in addition to standard clinical instruments at both early time point (2 week) and end treatment.
Evaluate antidepressant treatment effects in addition to standard clinical instruments.
Explore pharmacokinetic-pharmacodynamic (PK/PD) relationships for markers measured during active treatments.
Evaluate the antidepressant efficacy of GW679769 (80 to 120 mg/day) compared to placebo in subjects diagnosed with MDD.
Evaluate the safety and tolerability of GW679769 (80 to 120 mg/day) compared to placebo in subjects diagnosed with MDD.
Characterize the population pharmacokinetics (PK) of GW679769 (80 to 120 mg/day) in subjects with MDD.
Prediction of symptom severity and response to treatment using, for example, structural and functional MRI, EEG.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Subjects must have the ability to comprehend the key components of the consent form.
2. Male or female outpatients aged 18-50, inclusive.
3. A primary diagnosis of MDE associated with MDD, single episode or recurrent, according to DSM-IV-TR (296.2 or296.3), diagnosed through a comprehensive psychiatric evaluation [in conjunction with the Mini International Neuropsychiatric Interview (MINI), Clinician Rated Version 5.0], as assessed by a physician with adequate training in psychiatry (e.g. Postgraduate qualification in psychiatry).
4. Subjects must, in the investigator’s opinion based on the subject’s history, have met DSM-IV-TR criteria for their current MDE for at least 8 weeks prior to the Screening Visit.
5. Subjects with a Carroll Depression Scale-Revised (CDS-R) self-assessment total score of >= 17 and <=30 and Item 3 of the HDRS grouping (Suicidal Tendency) <=2 at the Screening Visit and Baseline Visit.
6. Subjects must have a CGI- Severity of Illness score >= 4 at the Baseline Visit.
7. Subjects with a history of peptic ulcer disease (PUD) with a known etiology must provide documentation by a gastroenterologist of the etiology of the PUD and that effective treatment was provided with full eradication of ulcers and symptoms. For such subjects appropriate steps must also have been taken to minimize reoccurrence risk (i.e. if PUD was nonsteroidal anti-inflammatory drug [NSAID] induced, the subject should no longer be taking NSAID medications; if cause was H. pylori, the subject should have been appropriately treated). For all subjects, regardless of whether there is a positive history of PUD, sites are required to document their H. pylori status at screening. Entry into the study is permitted for subjects who are seropositive for H. pylori, but treatment is recommended after study participation at the discretion of the Principal Investigator.
8. Women of childbearing potential must commit to consistent and correct use of an acceptable method of birth control that must be recorded in the source documentation at each visit; GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of a physician, are as follows:
a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal. For purposes of this study, postmenopausal is defined as one year without menses)
b. Child-bearing potential, has a negative serum pregnancy test result at screen and a negative pregnancy test at baseline (prior to study drug administration), and agrees to one of the following:
• Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject
• Oral contraceptives (either combined or progestogen only) with double-barrier method of contraception consisting of spermicide with either condom or diaphragm
• Women of child-bearing potential using an oral contraceptive in combination with a double-barrier method of contraception are required to continue to use this form of contraception for 6 weeks following discontinuation of study medication.
• Double-barrier method of contraception consisting of spermicide with either condom or diaphragm
• IUD with a documented failure rate of less than 1% per year
• Complete abstinence from intercourse for two weeks before exposure to the investigational product, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of three days, equivalent to five half lives)
a. If subjects indicate they will remain abstinent during the period described above, they must agree to follow GSK guidelines for the consistent and correct use of an acceptable method of birth control should they become sexually active.
9. Subject must read and write in English at a level sufficient to complete study-related assessments
|
|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Subjects whose symptoms of the MDE are better accounted for by another diagnosis.
2. Subjects with a history of schizophrenia, schizoaffective disorders or bipolar disorder.
3. Subjects have a positive urine test at screening for illegal drug use at the discretion of the Investigator, and/or a history of substance abuse or dependence (alcohol or drugs as defined by DSM-IV-TR criteria) within the past 12 months. Subjects have a blood alcohol level of >= 80 mg/dl or negative alcohol breath test at the Screening Visit. Note – subjects must be told to avoid consumption of alcoholic beverages for at least 8 hours prior to their Screening Visit.
4. Subjects are currently receiving regularly scheduled psychotherapy (individual or group), plan to initiate psychotherapy during the trial or have received regularly scheduled psychotherapy during the 12 week period prior to the Screening Visit.
5. Subjects have previously failed to respond to adequate courses (e.g. maximum labelled dosages for >= 4 weeks) of pharmacotherapy from two different classes of antidepressants or have failed to respond to an adequate course of paroxetine.
6. Subjects who, in the investigator's judgment, pose a homicidal or serious suicidal risk, have made a suicide attempt within the 6 months preceding the Screening Visit or who have ever been homicidal.
7. Subjects who have received electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the 6 months prior to the Screening Visit.
8. Subjects with any history of a seizure disorder (except for febrile seizures in childhood).
9. Subjects with an unstable medical disorder; or a disorder that would likely interfere with the action, absorption, distribution, metabolism or excretion of GW679769; or paroxetine, may pose a safety concern; or interfere with the accurate assessment of safety or efficacy.
10. Subjects with a history of myocardial infarction within one year prior to the Screening Visit.
11. Subjects have any screening laboratory value outside of the Sponsor-specified ranges at Screening Visit (see Appendix 7); testing may be repeated once to see if value returns to within range but any such laboratory abnormality must be resolved by the Baseline Visit.
12. Subjects have any laboratory abnormality that in the investigator's judgment is considered to be clinically significant and not resolved by the Baseline Visit (even if not outside of Sponsor-specified ranges in Appendix 7).
13. Subjects who are not euthyroid based on lab results at the Screening Visit. Subjects maintained on thyroid medication must be euthyroid for a period of at least six months prior to the Screening Visit.
14. Subjects have any screening electrocardiography (ECG) parameter outside of the Sponsor-specified ranges (see Appendix 8); the ECG may be repeated once to see if the parameter returns to within range but any such abnormality must be resolved by the Baseline Visit.
15. Subjects have any ECG finding that in the investigator's judgement is considered to be clinically significant and not resolved by the Baseline Visit (even if not outside of Sponsor-specified ranges in Appendix 8).
16. Subjects with active PUD and/or history of PUD of an unknown etiology.
17. Subjects who will likely require the use of the following medications:
a. Non-steroidal anti-inflammatory drug. Use of any dose of a non-steroidal anti-inflammatory drug (including aspirin or COX2 inhibitor) is permitted only when administered with an anti-secretory agent (a proton pump inhibitor or histamine-2 receptor antagonist)
b. Use of aspirin together with an NSAID including COX2 inhibitor is not permitted.
18. Subjects found to have stool positive for occult blood. If such a stool was obtained without the subject abstaining from red meat for three or more days prior, testing may be repeated once following such abstinence. If that stool is negative for occult blood by the Baseline Visit the subject is considered eligible.
19. Subjects with known or suspected iron deficiency.
20. Women who have a positive pregnancy test at the Screening Visit, at the Baseline (Randomization) Visit, or who are lactating or planning to become pregnant within the 4 months following the Screen Visit.
21. Subjects who have taken other psychoactive drugs within two weeks prior to the Baseline Visit or at any time during the Screening period:
a. All antidepressants including SSRI's (with the exception of fluoxetine, which requires four weeks)
b. Monoamine Oxidase Inhibitors (MAOIs), benzodiazepines, other psychoactive medications (including psychoactive herbal treatments, e.g., St. John's Wort, SAM-e)
c. Hypnotics, and all other sedatives (including sedating antihistamines if used for their sedating and/or hypnotic properties)
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Changes from baseline in brain functional activation measured by fMRI in amygdala and anterior cingulate cortex during implicit processing of negatively valent (sad and fearful) facial expressions produced by the treatments. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last visit of the subject undergoing the trial |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
Print
