E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major depressive disorder |
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E.1.1.1 | Medical condition in easily understood language |
Major depressive disorder |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057840 |
E.1.2 | Term | Major depression |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 |
Assessment of the efficacy of the two doses of S 47445 (15mg/day and 50mg/day) of S 47445 compared to placebo after a 8-week treatment period using the Hamilton Depression Rating Scale 17 items (HAM-D) |
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E.2.2 | Secondary objectives of the trial |
- Assessment of the response defined by the HAM-D total score decrease from baseline ≥ 50%
- Assessment of the efficacy of the two doses of S 47445 as compared to placebo on Global improvement and social functioning using Clinical Global Impression (CGI), Hospital Anxiety and Depression scale (HAD) and Sheehan Disability Scale (SDS)
- Assessment of the safety and the tolerance of the two doses of S 47445 compared to placebo
- Evaluation of the pharmacokinetics of S 47445 after repeated oral administration |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Outpatients
- Male or female aged between 18 (or legal age of majority in the country) and 65 years (inclusive),
- Fulfilling DSM-5 criteria for Major Depressive Disorder confirmed by the brief structured interview M.I.N.I. (single or recurrent episode, current episode ≤ 12 months, current depressive episode of moderate or severe intensity, with or without anxious distress, with or without melancholic features, without mixed features or atypical features, without seasonal pattern, without psychotic features, without catatonic features, without peripartum onset for the current episode)
- Patients treated for the current depressive episode with an antidepressant treatment with SSRI (fluoxetine, citalopram, paroxetine, escitalopram or sertraline) given in monotherapy at recommended dose for at least 6 weeks and no more than 4 months and with a stable dosage for at least 3 weeks
- HAM-D total score ≥ 20
- Clinical Global Impression Severity of illness (item 1): 6 ≥ CGI-S ≥ 4
- Antidepressant Treatment Response Questionnaire (ATQR) < 50% for the current SSRI
- Absence of any abnormalities likely to interfere with the conduct of the study (ECG, vital signs, laboratory tests, medical history) |
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E.4 | Principal exclusion criteria |
- Depressive episode of mild intensity according to DSM-5 criteria
- All types of depressive episodes other than those occurring in a Major Depressive Disorder (Persistent Depressive Disorder (Dysthymia) according to DSM-5 criteria, including persistent depressive disorder with intermittent or persistent major depressive episode according to DSM-5, Premenstrual Dysphoric Disorder, Substance Induced Depressive Disorder, Depressive Disorder due to another Medical Condition, Other Specified or Unspecified Depressive Disorder, Bipolar Disorder I or II, depressed episode, Schizoaffective Disorder (Depressive or Bipolar type))
- Depression onset within 12 months after a stroke
- Suicidal risk defined as a score > 3 on the item 3 of the HAM-D scale or in the investigator’s opinion
- Lactose intolerance
- Patients with hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
- Resistant depression for the current episode (patients who have not responded to 1 previous antidepressant treatment before the SSRI taken at an appropriate dose)
- Current panic disorder
- Obsessive compulsive disorder
- Current post traumatic stress disorder, current acute stress disorder
- Current or past psychotic disorder
- Any severe personality features |
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E.5 End points |
E.5.1 | Primary end point(s) |
HAM-D total score expressed as change from baseline value
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Depressive symptoms:
- HAM-D total score at each visit,
- Response to treatment defined by HAM-D total score decrease from baseline ≥ 50%
- Clinical Global Impression scale (CGI), item 1 (Severity of depression) and item 2 (global Improvement) scores, response to treatment (CGI item 2 = 1or 2)
- Hospital Anxiety and Depression Scale (HAD), Anxiety and Depression sub-scores
Social functioning
- Sheehan Disability Scale (SDS) scores (Work, social and family life)
Safety criteria:
- Adverse Events
- Body Weight and BMI
- Laboratory tests (haematology and biochemistry)
- 12-lead ECG
- Vital signs (standing and supine Systolic and Diastolic Blood Pressure, Heart rate)
- Columbia-Suicide Severity Rating Scale (C-SSRS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- HAM-D: at W0, W2, W4, W6 and W8
- CGI item 1 at W0, W2, W4, W6 and W8 and item 2 at W2, W4, W6 and W8
- HAD: at W0, W2, W4, W6 and W8
- SDS: at W0, W2, W4, W6 and W8
- Adverse Events: all over the study
- Body Weight and BMI: at W4 and W8
- Laboratory tests: at W4 and W8
- 12-lead ECG: at W4 and W8
- Vital signs: at W0, W2, W4, W6 and W8
- C-SSRS: at W0, W2, W4, W6 and W8 |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 | No |
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 |
Bulgaria |
Czech Republic |
Finland |
Hungary |
Russian Federation |
Slovakia |
Ukraine |
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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
|
Last visit last patient as stated in the protocol |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |