| 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 | 11.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025453 |
| E.1.2 | Term | <Manually entered code. Term in E.1.1> |
|
| 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 |
| The primary objective of this study is to evaluate the efficacy of 3 fixed doses of SSR411298 (10, 50 or 200 mg daily) compared to placebo, in elderly patients with Major Depressive Disorder (MDD), based on the 17-item Hamilton Depression Rating Scale (HAM-D). |
|
| E.2.2 | Secondary objectives of the trial |
•To evaluate the tolerability and safety of an 8-week treatment with SSR411298 versus placebo in elderly patients with MDD
•To evaluate the effect of SSR411298 on disability, anxiety, cognitive function, sleep, and pain and somatic symptoms related to depression, and bone markers
•To assess SSR411298 plasma concentrations
•To assess plasma endocannabinoid concentrations |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female outpatient ≥60 years of age.
2. Diagnosis of major depressive disorder (MDD)
•defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria
•confirmed by the Mini International Neuropsychiatric Interview (MINI)
•recurrent episode for at least one month prior to Visit 1
•episode may be isolated or superimposed on dysthymic disorder and may meet criteria for atypical or melancholic features
•may also meet criteria for anxiety disorder comorbid disorders (such as panic disorder with or without agoraphobia, social phobia or obsessive-compulsive disorder), provided that depression is the predominant disorder in terms of severity and subjective distress.
3. Given written informed consent. |
|
| E.4 | Principal exclusion criteria |
-Exclusion criteria related to study methodology
1. Unable to comply with study protocol requirements.
2. HAM-D total score <16 at screening Visit 1 (Day -7) or baseline Visit 2 (Day -1)
3. Montgomery-Asberg Depression Rating Scale (MADRS) total score <22 at
screening Visit 1 (Day -7) or baseline Visit 2 (Day -1).
4. Mini-Mental State Examination (MMSE) < 23.
5. Significant suicide risk:
•score of >5 on the suicidal thoughts item of the MADRS (item 10) at screening Visit 1
(Day -7) or baseline Visit 2 (Day -1)
•or score of >3 on the suicide item (item 3) of the HAM-D at screening Visit 1 (Day -7)
or baseline Visit 2 (Day -1);
•or a current suicide risk score ≥10 from Module C (suicidality) of the MINI.
6. History of a suicide attempt within the past 2 years.
7. Duration of the current depressive episode is greater than 2 years.
8. Current depressive episode has been diagnosed with psychotic features, catatonic
features, or seasonal pattern, or is secondary to a general medical condition (DSM-IV-TR 293.83).
9. History or presence of bipolar disorder or psychotic disorder, according to the item D and L of the MINI.
10. Post-traumatic stress disorders, anorexia nervosa and bulimia nervosa within the past 6 months, according to the items I, M and N of the MINI.
11. Meets DSM-IV-TR criteria for Antisocial Personality Disorder or Borderline
Personality Disorder.
12. Alcohol dependence or abuse or substance dependence or abuse in the past 12 months, according to the MINI, except nicotine or caffeine dependence.
13. Used the following prior to entry into the Randomized Treatment Phase:
a) Any monoamine oxidase inhibitors (MAOIs) within the past 2 weeks,
b) Any other antidepressant, antipsychotic, anxiolytic, sedative-hypnotic, or mood
stabilizer (lithium, anticonvulsants) within the past 7 days, except permitted
concomitant medications as defined in Section 3.
14. Prohibited concomitant treatments as defined in Section 3.
15. Treatment with electroconvulsive therapy (ECT) within the past 1 year.
16. Initiated, stopped, or changed frequency and/or nature of psychotherapy within the past 6 weeks.
17. Tested positive for any illicit drug included in the urine drug screen at Visit 1 (Day-7).
18. Abnormal thyroid function (ie, out of range TSH blood level at Visit 1) unless patients are receiving thyroid replacement therapy at a stable dose for the past 3 months and/or are considered clinically euthyroid.
19. Severe progressive or unstable cardiovascular, renal, hepatic, respiratory,
hematological, endocrinological, neurological, or other somatic disease that, according to the Investigator’s judgment, might interfere with the evaluation of study medication.
20. Significantly abnormal hepatic clinical laboratories: ALT, AST, or GGT >3x ULN; Tbili >ULN).
21. Participation in a clinical trial of an experimental therapy within the past 30 days or concomitant use of any FAAH inhibitor.
-Exclusion criteria related to escitalopram
21. Clinical history of non-response (4-week treatment at therapeutic dose) or intolerance to escitalopram or citalopram.
22. Hypersensitivity to escitalopram or citalopram or any of the inactive ingredients of the formulation.
-Exclusion criteria related to SSR411298
23. Using CYP3A strong inhibitors and inducers within the past 7 days.
24. Females who are not at least one year post-menopausal. (Post-menopausal is defined as the time after which a woman has experienced twelve consecutive months of amenorrhea, and menopausal symptoms, if significantly present, have become less intense and/or less frequent).
25. For male patients with partners of child bearing potential, unwillingness to use the acceptable method of contraception during the study. Condom plus occlusive cap
(diaphragm or cervical/vault caps) plus spermicidal foam/gel/film/cream/suppository is
the acceptable method of contraception for this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy criterion is the difference between treatment groups in the mean change from baseline to Visit 8 (Day 56) on the 17-item Hamilton Depression Rating Scale (HAM-D). |
|
| 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 | Yes |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| 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 | Yes |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned days | 8 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 8 |
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