E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Major Depressive Disorder |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 3.3 |
E.1.2 | Level | P.T. |
E.1.2 | Classification code | 10025453 |
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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 assess the agomelatine superiority to fluoxetine, using the Hamilton Depression Rating Scale 17 items, after a 8-week treatment in out-patients suffering from severe Major Depressive Disorder.
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E.2.2 | Secondary objectives of the trial |
To provide additional sleep, anxiety and safety data on agomelatine in this population.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Selection criteria : male or female out-patients, aged of 18 (or minimum legal age) to 65 years (both inclusive), - Fulfilling DSM-IV-TR criteria for Major Depressive Disorder, of severe intensity (HAM-D-17 total score greater than or equal to 25 and CGI severity of illness greater than or equal to 4): . single or recurrent episode > or = 4 weeks . with or without melancholic features, . without seasonal pattern, . without psychotic features, . without post partum onset. - All other concomitant psychiatric disorders are not allowed and will be documented using the brief structured interview MINI - Requiring an antidepressant treatment
Inclusion criteria : - The investigator will check during the inclusion visit that all selection criteria are still fulfilled, - HAM-D-17 items total score greater than or equal to 25 without a decrease from selection visit more than 20%, - Sum of items H1, H2, H5, H6, H7, H8, H10 and H13 of HAM-D-17 greather than or equal to 55% of HAM-D-17 total score at W0, - CGI item 1 still greater or equal to 4, - Available laboratory tests and 12-lead ECG results for the inclusion visit, - Physical examinations (BP, HR, body weight) performed at inclusion visit.
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E.4 | Principal exclusion criteria |
Non-selection criteria related to depression : - All types of depression other than Major Depressive Disorder, including Bipolar Disorder I and II, Double Depression (Major Depressive Disorder and Dysthymic Disorder), chronic depression (defined as depression with a duration of the episode longer than 2 years), Schizoaffective Disorder of depressive type, depression with psychotic features, - Current depressive episode having not responded to 2 different previous antidepressant treatments of at least 4 weeks for each one at an appropriate dose (including fluoxetine), - Marked suicidal intent and/or known suicidal tendencies for the current episode defined as a score of 4 at the item 3 of the HAM-D-17 or the investigator's opinion based on the patient’s medical history, previous suicide attempts, quality of social and familial support, - Patient treated with ECT within the last 3 months before selection or requiring ECT at present (according to investigator’s clinical judgment), - Insight-oriented and structured psychotherapy (interpersonal therapy, psychoanalysis, cognitive behavioural therapy) started within the 3 months before selection, - Light-therapy received within 2 weeks before selection,
Non-inclusion criteria : - Any non-selection criteria which could have appeared after the selection visit, - Any clinically relevant abnormality detected during the physical examination, ECG or laboratory tests likely to interfere with the study conduct or evaluations, - gGT or transaminases values > 3 times the upper limit or/and creatininemia > 150 mmol/l. - Treatment with thyroid hormones started, stopped or modified within 3 months prior to inclusion. They should remain at a stable dose until W8 visit, - Menopause hormone replacement therapy started, stopped or modified within 3 months prior to inclusion. They should remain at a stable dose until W8 visit, - b-blockers started, stopped or modified within 4 weeks prior to inclusion. They should remain at a stable dose until W8 visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to assess the agomelatine superiority to fluoxetine after a 8-week treatment period.
The primary efficacy criterion is : HAM-D-17 total score.
The secondary efficacy criteria are : - severity of illness, Global improvement, issued from CGI scale, - LSEQ scores, - HAM-A scores.
Safety criteria : - Adverse events, - Laboratory parameters, - Blood pressure, heart rate, - Body weight and BMI, - ECG.
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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 | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 |
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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
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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 | 6 |
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 | 6 |