| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder (MDD) |
|
| 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 |
| To evaluate the antidepressant efficacy of GW679769 (80 to 120 mg/day) versus placebo |
|
| E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of GW679769
To provide data to analyse the relationship between response and dose/plasma concentration of GW679769
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Subjects must have the ability to comprehend the key components of the consent
form.
Male or female outpatients aged 18-64, inclusive.
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).
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.
Subjects with a Carroll Depression Scale-Revised (CDS-R) self-assessment total
score of ≥24 at the Screen Visit and Baseline Visit.
Subjects must have a CGI- Severity of Illness score ≥ 4 at the Baseline Visit.
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, either before or after study
participation at the discretion of the Principal Investigator.
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 urine dipstick 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
• 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)
c. 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.
|
|
| E.4 | Principal exclusion criteria |
Subjects whose symptoms of the MDE are better accounted for by another diagnosis
Subjects with history of schizophrenia, schizoaffective disorders or bipolar
disorder
Subjects have positive urine test at screening for illegal drug use and/or a history of substance abuse or dependence
Subjects have a blood alcohol level of ≥ 15 mg/dl (0.015%) at the Screening Visit
Subjects are currently receiving regularly scheduled psychotherapy, plan to initiate psychotherapy during the trial or have received regularly scheduled psychotherapy during the 12 weeks prior to the Screening Visit
Subjects have previously failed to respond to adequate courses of pharmacotherapy from two different classes of antidepressants or have failed to respond to an adequate course of paroxetine
Subjects who, in the investigator's judgement, pose a homicidal or serious suicidal
risk, have made a suicide attempt within the 6 months preceding screening or who
have ever been homicidal
Subjects who have received electroconvulsive therapy (ECT) or transcranial
magnetic stimulation (TMS) within the 6 months prior to the Screening Visit.
Subjects with any history of a seizure disorder
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
Subjects with a history of myocardial infarction within 1 year prior to the
Screening Visit
Subjects have any screening laboratory value outside of the Sponsor-specified ranges at Screening Visit
Subjects have any laboratory abnormality that in the investigator's judgement is
considered to be clinically significant and not resolved by the Baseline Visit
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 6 months prior to the Screening Visit
Subjects have any screening electrocardiography (ECG) parameter outside of the
Sponsor-specified ranges
Subjects have any ECG finding that in the investigator's judgement is considered to
be clinically significant and not resolved by the Baseline Visit
Subjects with active PUD and/or history of PUD of an unknown etiology
Subjects who will likely require the use of the following medications:
• NSAIDs (unless administered concomitantly with an anti-secretory agent, i.e., proton-pump inhibitor or histamine-2 receptor antagonist and administered in the absence of concomitant aspirin therapy); or
• concomitant use of aspirin and COX2 inhibitors.
Subjects found to have stool positive for occult blood
Subjects with known or suspected iron deficiency
Women who have a positive serum HCG pregnancy test at the Screening Visit, a
positive urine dipstick test at the Baseline (Randomization) Visit, or who are
lactating or planning to become pregnant within the 4 months following the Screen
Visit
Subjects who have taken other psychoactive drugs within two weeks prior to the
Baseline Visit or at any time during the Screening period:
• all antidepressants including SSRI's
• Monoamine Oxidase Inhibitors (MAOIs), benzodiazepines, other psychoactive
medications (including psychoactive herbal treatments, e.g., St. John's Wort,
SAM-e)
• Hypnotics, and all other sedatives (including sedating antihistamines if used for
their sedating and/or hypnotic properties)
Subjects who have taken other (non-psychotropic) drugs, metabolized via the cytochrome P450 3A4 or 2C8 pathway, or a substrate of P-glycoprotein, with a narrow therapeutic index within 2 weeks (or 5 half lives, whichever is longer) prior to the Baseline Visit.
Subjects who have taken other (non-psychotropic) drugs that are potent or moderate inhibitors or inducers of the cytochrome P450 3A4 pathway within 2 weeks (or 5 half lives, whichever is longer) prior to the Baseline Visit
Subjects who have had hypersensitivity or intolerance to NK1 antagonists or SSRI’s
Subjects who have participated in a clinical trial involving GW679769
Subjects who are currently participating in another clinical trial in which the subject
is or will be exposed to an investigational or non-investigational drug or device, or
has done so within the preceding month for studies unrelated to MDD, or 6 months
for studies related to MDD
Subjects who have no contact with an adult on a daily basis.
Subjects who take triptan medications (e.g. sumatriptan, naratriptan, zolmitriptan),
the antibiotic linezolid or tryptophan
Subjects with a history of myopathy or rhabdomyolysis
Subjects participating in regular strenuous exercise (e.g., greater than 5 hours per
week running, swimming, weightlifting or any other similar physical activity,
including that undertaken in the course of a subject’s employment) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) total score. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| 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 | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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