| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025453 |
| E.1.2 | Term | Major depressive disorder NOS |
|
| 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 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. |
|
| E.2.2 | Secondary objectives of the trial |
• 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 (TNFα 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
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 19; general interest), energy (item 20; energy level) and psychomotor
retardation (item 23; feeling slowed down).
IDS-C when measured at the Screening visit and at the Randomization visit (Week
0)
• a total score of ≥36, and
• a score ≥ 1 on Items representing mood (item 5), interest (item 19), energy (item
20), and psychomotor retardation (item 23) and.
• a change (either increase or decrease) in total score at Randomization of no more
than 25% from Screening |
|
| E.4 | Principal 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 the Randomization visit, or who are planning to become pregnant within the next 16 weeks following the Screening visit.
24. Subjects have any screening (ECG) parameter outside of the Sponsor-specified ranges; view protocol.
25. The subject is currently receiving or has received a chronic biological or pharmacologic anti-inflammatory therapy: view protocol for further information.
26. Subjects who have taken other psychoactive drugs, unless otherwise stated in this protocol, within 1 week or 5 half lives (whichever is greater) prior to the Randomization visit:
• All antidepressants including SSRIs, Inhibitors (MAOIs), benzodiazepines, other psychoactive medications (including psychoactive herbal treatments, e.g., St. John’s Wort, SAM-E) for further information view protocol.
27. Subjects who have been exposed to an investigational drug within 6 months prior to Randomization.
28. Subjects who, in the opinion of the investigator, would be noncompliant with the visit schedule or study procedures, (view protocol).
29. Subjects who are treatment resistant. For the purpose of the study, treatment resistance is defined as a failure to respond to two or more antidepressants from two different classes, when treated with an adequate dose (maximum-labelled/ tolerated dose) for an adequate duration (≥4weeks).
30. Subjects who have donated a unit of blood within the previous month or intends to donate in the month after completing the study.
|
|
| E.5 End points |
| E.5.1 | 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. |
|
| 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 | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Trascriptomic (RNA analysis) |
|
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| Exploratory, Adaptive design |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 9 |
| 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 | No |
| 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
|
| End of trial is marked by reaching LSLV. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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