Efficacy and Safety of S 47445 Versus Placebo as Adjunctive Treatment in Depressed Patients Not Fully Recovered From Depressive Symptoms With a Current Antidepressant Treatment

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of S47445 versus placebo as adjunctive treatment of Major Depressive Disorder in patients with an inadequate response to antidepressant therapy.

Official Title
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Efficacy and Safety of S 47445 Versus Placebo as Adjunctive Treatment of Major Depressive Disorder in Patients With an Inadequate Response to Antidepressant Therapy: A Randomised, Double-blind, Placebo Controlled International, Multicentre Study

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: S47445 15mg
* Drug: S47445 50mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients 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) 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S47445 15mg<br> | Drug: S47445 15mg<br>* One tablet of S47445 15 mg taken orally once a day during breakfast concomitantly to the current selective serotonin reuptake inhibitor treatment, starting the day after inclusion visit and ending the day of the W8 visit.<br>|
| Experimental: S47445 50mg<br> | Drug: S47445 50mg<br>* One tablet of S47445 50 mg taken orally once a day during breakfast concomitantly to the current selective serotonin reuptake inhibitor treatment, starting the day after inclusion visit and ending the day of the W8 visit.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* One tablet of placebo taken orally once a day during breakfast concomitantly to the current selective serotonin reuptake inhibitor treatment, starting the day after inclusion visit and ending the day of the W8 visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale (HAM-D) total score expressed as change from baseline value |  | 8 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAM-D total score | Depressive symptoms | at week 0, week 2, week 4, week 6 and week 8 | 
| Response to treatment defined by HAM-D total score decrease from baseline ≥ 50% | Depressive symptoms | at week 0, week 2, week 4, week 6 and week 8 | 
| Clinical Global Impression scale (CGI), item 1 (Severity of depression) and item 2 (global Improvement) scores, response to treatment (CGI item 2 = 1 or 2) | Depressive symptoms | CGI item 1 at week 0, week 2, week 4, week 6 and week 8 and item 2 at week 2, week 4, week 6 and week 8 | 
| Hospital Anxiety and Depression Scale (HAD), Anxiety and Depression sub-scores | Depressive symptoms | at week 0, week 2, week 4, week 6 and week 8 | 
| Sheehan Disability Scale (SDS) scores (Work, social and family life) | Social functioning | at week 0, week 2, week 4, week 6 and week 8 | 
| Adverse Events | Safety criterion | through study completion (an average of 12 weeks) | 
| Body Weight | Safety criterion | at week 4 and week 8 | 
| BMI | Safety criterion | at week 4 and week 8 | 
| Laboratory tests (haematology and biochemistry) | Safety criterion | at week 4 and week 8 | 
| 12-lead ECG | Safety criterion | at week 4 and week 8 | 
| Vital signs (standing and supine Systolic and Diastolic Blood Pressure, heart rate) | Safety criterion | at week 0, week 2, week 4, week 6 and week 8 | 
| Columbia-Suicide Severity Rating Scale (C-SSRS) | Safety criterion | at week 0, week 2, week 4, week 6 and week 8 |