Randomised Placebo-controlled Venlafaxine-referenced Study of Efficacy and Safety of 5 and 10 mg of Vortioxetine (Lu AA21004) in Acute Treatment of Major Depressive Disorder in Adults

Study Overview
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Brief Summary
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The purpose of this Venlafaxine-referenced study is to evaluate the efficacy, safety and tolerability of two fixed doses of Vortioxetine in the acute treatment of Major Depressive Disorder (MDD).

Official Title
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Double-blind, Randomised, Placebo-controlled Study Comparing the Efficacy and Safety of Two Fixed Dosages of a Novel Antidepressant Compound to That of Placebo in Patients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Vortioxetine (Lu AA21004)
* Drug: Venlafaxine XL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MDE as primary diagnosis according to DSM-IV-TR criteria (classification code 296.xx) Current MDE duration of at least 3 months and less than 12 months The patient has a MADRS total score >=30 Exclusion Criteria: Any current psychiatric disorder other than MDD as defined in the DSM-IV TR Any substance disorder within the previous 6 months Female patients of childbearing potential who are not using effective contraception Use of any psychoactive medication 2 weeks prior to screening and during the study Other protocol-defined inclusion and exclusion criteria may apply.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* capsules, daily, orally<br>|
| Experimental: Vortioxetine (Lu AA21004) 5 mg<br> | Drug: Vortioxetine (Lu AA21004)<br>* encapsulated tablets, daily, orally<br>* Other names: Brintellix;|
| Experimental: Vortioxetine (Lu AA21004) 10 mg<br> | Drug: Vortioxetine (Lu AA21004)<br>* encapsulated tablets, daily, orally<br>* Other names: Brintellix;|
| Other: Venlafaxine XL 225 mg<br>Active Reference | Drug: Venlafaxine XL<br>* capsules, daily, orally<br>* Other names: Effexor®;|

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 After 6 Weeks of Treatment | 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. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in MADRS Total Score After 1 Week of Treatment |  | Baseline and Week 1 | 
| Change From Baseline in HAM-D 24 Total Score After 6 Weeks of Treatment | The 24-item Hamilton Depression Rating Scale (HAM-D) is based on the 21-item HAM-D plus an additional 3 items (helplessness, hopelessness, and worthlessness). The observer makes his/her assessment on the basis of a specific statement, content, tone, facial expression, and gestures of the patient during the interview, and scores each item from 0 to 2 or 0 to 4. Total score from 0 to 76. The higher the score, the more severe. | Baseline and Week 6 | 
| Change From Baseline in HAM-A Total Score After 6 Weeks of Treatment | 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. The higher the score, the more severe. | Baseline and Week 6 | 
| Change From Baseline in CGI-S Score After 6 Weeks of Treatment | 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. | Baseline and Week 6 | 
| Change in Clinical Status Using CGI-I Score at Week 6 | 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. | Week 6 | 
| Proportion of Responders at Week 6 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline) |  | Week 6 | 
| Proportion of Remitters at Week 6 (Remission is Defined as a MADRS Total Score <=10) |  | Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major depressive disorder, Placebo-controlled, Active reference, Multicenter study, Randomised study, Acute treatment