A Study of Vortioxetine (Lu AA21004) in Comparison to Agomelatine in Adults Suffering From Major Depression With Inadequate Response to Previous Medication

Study Overview
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Brief Summary
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The objective of the present study is to evaluate whether vortioxetine (10 or 20 mg/day) is at least as effective as agomelatine (25 to 50 mg/day) in patients with depressive symptoms that showed inadequate response to Serotonin Reuptake Inhibitors (SRI) antidepressants.

Official Title
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A Randomised, Double-blind, Parallel-group, Active-controlled, Flexible Dose Study Evaluating the Effects of [Vortioxetine] Lu AA21004 Versus Agomelatine in Adult Patients Suffering From Major Depressive Disorder With Inadequate Response to Antidepressant Treatment

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Vortioxetine (Lu AA21004)
* Drug: Agomelatine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is being treated with a serotonin reuptake inhibitor (SRI) antidepressant (monotherapy) that was prescribed to treat Major Depressive Episode (DSM-IV-TR criteria) The response to the current SRI treatment is inadequate and patient agrees to discontinue the current SRI at the baseline Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥22 at the Screening Visit and Baseline The patient, if a woman, must: agree not to try to become pregnant during the study, AND use adequate, highly effective contraception Exclusion Criteria: The patient has any current Axis I disorders (DSM-IV criteria) other than Major Depressive Disorder (MDD), General Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD) The patient is at significant risk of suicide The patient is currently receiving formal psychotherapy or other psychoactive medications Other protocol-defined inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vortioxetine 10 mg or 20 mg<br> | Drug: Vortioxetine (Lu AA21004)<br>* encapsulated tablets, daily, orally<br>* Other names: Brintellix®;|
| Active Comparator: Agomelatine 25 mg or 50 mg<br> | Drug: Agomelatine<br>* encapsulated tablets, daily, orally<br>* Other names: Valdoxan®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in MADRS Total Score at Week 8 | The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in MADRS Total Score at Week 12 |  | Baseline and Week 12 | 
| Change From Baseline in HAM-A Total Score at Week 8 | The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behaviour at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic, and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total score from 0 to 56; higher score indicates greater anxiety, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. | Baseline and Week 8 | 
| Change From Baseline in HAM-A Total Score at Week 12 |  | Baseline and Week 12 | 
| Change From Baseline in CGI-S Score at Week 8 | The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating. Higher score indicates that the subject is more ill, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. | Baseline and Week 8 | 
| Change From Baseline in CGI-S Score at Week 12 |  | Baseline and Week 12 | 
| Change in Clinical Status Using CGI-I Score at Week 8 | The Clinical Global Impression - Global Improvement (CGI-I) is a 7-point scale rated from 1 (very much improved) to 7 (very much worse). The investigator rated the patient's overall improvement relative to baseline, whether or not, in the opinion of the investigator, this was entirely due to the drug treatment. Higher score = more affected. | Week 8 | 
| Change in Clinical Status Using CGI-I Score at Week 12 |  | Week 12 | 
| Proportion of Patients Who Respond at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline) |  | Baseline and Week 8 | 
| Proportion of Patients Who Respond at Week 12 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline) |  | Baseline and Week 12 | 
| Proportion of Patients Who Are in Remission at Week 8 (Remission is Defined as a MADRS Total Score <=10) |  | Week 8 | 
| Proportion of Patients Who Are in Remission at Week 12 (Remission is Defined as a MADRS Total Score <=10) |  | Week 12 | 
| Change From Baseline in SDS Total Score at Week 8 | The Sheehan Disability Scale (SDS) comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). The higher the score, the more severe, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms. | Baseline and Week 8 | 
| Change From Baseline in SDS Total Score at Week 12 |  | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Multimodal antidepressant